TYPE Review PUBLISHED 25 October 2023 DOI 10.3389/fvets.2023.1279506 Potential benefits of yeast OPEN ACCESS Saccharomyces and their derivatives in dogs and cats: a EDITED BY Tao Wang, Jilin Agricultural University, China REVIEWED BY Chunyin Geng, review Yanbian University, China Xiaofeng Xu, College of Animal Science and Technology, Marta Maturana 1, Lorena Castillejos 1, Susana M. Martin-Orue 1, China Anaelle Minel 2, Olivia Chetty 2, Ananda P. Felix 3 and Achraf Adib *CORRESPONDENCE Lesaux 2* Achraf Adib Lesaux a.adiblesaux@phileo.lesaffre.com 1 Animal Nutrition and Welfare Service (SNiBA), Department of Animal and Food Science, Universitat Autònoma de Barcelona (UAB), Bellaterra, Spain, 2 Department of Research & Development, Phileo by RECEIVED 18August 2023 Lesaffre, Marcq-en-Baroeul, France, 3 Department of Animal Science, Federal University of Paraná, ACCEPTED 09 October 2023 Curitiba, Brazil PUBLISHED 25 October 2023 CITATION Maturana M, Castillejos L, Martin-Orue SM, Yeast Saccharomyces and its derivatives have been largely used in livestock and Minel A, Chetty O, Felix AP and Adib Lesaux A (2023) Potential benefits of yeast poultry nutrition for their potential positive impact on growth, performance, and Saccharomyces and their derivatives in dogs general health. Originally included in animal diets as a source of protein, yeasts can and cats: a review. also offer a wide range of by-products with interesting bioactive compounds that Front. Vet. Sci. 10:1279506. doi: 10.3389/fvets.2023.1279506 would confer uses beyond nutrition. Although its supplementation in livestock, poultry and even in humans is well documented, the available body of literature on COPYRIGHT © 2023 Maturana, Castillejos, Martin-Orue, the use of yeast and its derivatives in companion animals’ food, mainly dogs and Minel, Chetty, Felix and Adib Lesaux. This is an cats’ diets, is still developing. Despite this, gut microbiota modulation, immune open-access article distributed under the terms system enhancement or decreasing of potentially pathogenic microorganisms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction have been reported in pets when using these products, highlighting their possible in other forums is permitted, provided the role as probiotics, prebiotics, and postbiotics. This review attempts to provide the original author(s) and the copyright owner(s) reader with a comprehensive on the effects of Saccharomyces and its derivatives are credited and that the original publication in this journal is cited, in accordance with in pets and the possible mechanisms that confer their functional properties. accepted academic practice. No use, distribution or reproduction is permitted which KEYWORDS does not comply with these terms. companion animals, prebiotics, probiotics, postbiotics, yeast 1. Introduction As the pet food industry keeps steadily growing annually, so does the demand for functional ingredients in dogs and cats’ diets. Owners look for ingredients that can provide additional health benefits beyond basic nutrition, echoing the functional foods trend already established in humans. Examples of these ingredients are omega-3 fatty acids, probiotics/prebiotics/ postbiotics, or plants and vegetables’ extracts. Yeasts may also represent a good candidate. There are about 500 different yeasts species and some of them have been used both in humans and animals, especially livestock, for many years, Saccharomyces cerevisiae (S. cerevisiae or SC) being the predominant one. In this review, we will specifically focus on the use of S. cerevisiae, referring to it also as yeast. Although the use of yeast in livestock and poultry feed has been widely reviewed, there is still a lack of information about the effects on dogs and cats, admittedly the number of studies is increasing. Moreover, despite the many beneficial health effects reported, the supplementation of yeast-based products has not always resulted in consistent effects, and the precise mode of action of these compounds has been difficult to determine. Thus, the aim of this review is to Frontiers in Veterinary Science 01 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 provide an overview on the use of Saccharomyces and/or their host” (3). The probiotic role of Saccharomyces cerevisiae var. derivatives, as a functional ingredient in pet food, discussing its boulardii (S. boulardii), a strain of the same genus as SC, nearly general possible modes of action with a specific focus on in vivo identical at a molecular level but physiologically different (4), is studies in companion animals. well established. However the probiotic role of S. cerevisiae needs further investigation, although some recent studies in dogs reported positive and promising results on modulation of 2. Saccharomyces composition and fermentative metabolites and microbiota composition and function products (5). On the other hand, yeast lysates, yeast extracts, and YCW components, mostly MOS and β-glucans, could be considered Yeasts cells intracellular composition includes amino acids, prebiotics and their use is more extended, with more studies peptides, carbohydrates, salts, vitamins, monosodium glutamate, reporting benefits on both human and animal health (1, 6). nucleic acids, enzymes, and cofactors. On the other hand, yeast cell Prebiotics are defined by the ISAPP as “a substrate that is selectively wall (YCW) is mostly formed by Beta-glucans (β-glucans), utilized by host microorganisms conferring a health benefit” (7). glycoproteins, and mannan oligosaccharides (MOS), and to a lesser Lastly, yeast culture, also known as Saccharomyces cerevisiae extent by chitin. There are different forms of yeasts being studied, fermentation product (SCFP), would pertain to the still recent ranging from viable yeast cells to purified components of the cell term “postbiotics” defined by the ISAPP as “preparation of wall, as shown in Table 1. From primary yeast cultures that inanimate microorganisms and/or their components that confers undergo propagation and fermentation steps, yeasts by-products a health benefit on the host” (8). are obtained via downstream processing (1, 2). Live yeast cells can be inoculated in specific culture media to ferment it and subsequently be dried, forming a yeast culture containing a wide 3. Saccharomyces as a functional variety of metabolic products. Yeast cells can also undergo a ingredient: modes of action process of hydrolysis or autolysis to obtain yeast lysates that contain both intracellular and cell wall fractions. However, 3.1. Microbiota improvement intracellular components and carbohydrates of the cell wall can also be found separately as yeast extract and cell wall products, A balanced gut microbiome is of vital importance for the respectively. health of the host and yeasts have been proven to cause shifts in Most of the yeast-based products available in the European the bacteria population of the gastrointestinal tract in several market are registered under the European Food Safety Authority species (9, 10). In vitro studies reported that the association of (EFSA) category of zootechnical additives, and subcategories of gut some strains of Saccharomyces and Lactobacillus rhamnosus exert microbiota stabilizers or digestibility enhancers, depending on the a protective effect on human microbiota following antibiotic product and target species. Whereas dried yeast is used for its administration (11) or against pathogenic bacteria (12). The use of nutritional value as a specialty amino acid, vitamin and mineral yeast β-glucan also promoted the growth of Bifidobacterium supplement, the rest of the products could fall under the definitions longum and other health-promoting gut microbiota in a study of probiotics, prebiotics, and postbiotics established by the simulating human saliva, gastric and intestinal digestion (13). International Scientific Association for Probiotics and Prebiotics Similarly, mannan and MOS derived from yeast were able to grow (ISAPP). Active dry yeast is formed by live yeast cells and acts as a specific lactic acid bacteria strains in vitro and beneficial probiotic, defined by ISAPP as “live microorganisms that when Bacteroides in humans (14, 15). Thus, yeast and yeast-based administered in adequate amounts, confer a health benefit on the products may potentially promote host’s gut health. TABLE 1 Most common Saccharomyces cerevisiae products added in animal feed, with its production process and the major composition (1). Product Process Composition Dried yeast (also dehydrated primary yeast) Drying of whole yeast cells (high temperature). Biomass of dead yeast cells. Active dry yeast (also dehydrated active yeast or live Drying of whole yeast cells. Live yeast cells. yeast) Yeast culture (also dehydrated yeast culture or SCFP Inoculation of live yeast cells in a specific culture Yeast biomass (residual viable cells, dead cells, and yeast cell in the case of Saccharomyces cerevisiae) medium followed by controlled fermentation and wall fragments), fermentation metabolites, and residual growth drying. medium. Lysate yeast (also hydrolyzed yeast /hydrolysates or Hydrolysis or autolysis of whole yeast cells. B vitamins, peptides, amino acids, glutamic acid, nucleotides, autolyzed yeast/autolysates) minerals, mannan oligosaccharides, and β-glucans. Yeast cell wall components Centrifugation after the hydrolysis/autolysis of the Mannan oligosaccharides and β-glucans (together or yeast. individualized). Yeast extract Centrifugation after the hydrolysis/autolysis of the B vitamins, peptides, amino acids, glutamic acid, nucleotides, yeast. and minerals. SCFP, Saccharomyces cerevisiae fermentation product. Frontiers in Veterinary Science 02 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 3.2. Immune system enhancement enhancement of immunoglobulins production by the host, and releasing of proteases that destroy certain toxins, among others The supplementation of yeast products can modulate the immune (28, 29). system through changes in the innate and adaptative response. It is One of the most frequent protection mechanisms of yeasts that thought that the main responsible of these properties are the β-glucan can be found in the literature is the capacity of binding pathogenic and MOS present in yeast. The specific changes are different bacteria, avoiding its union with the host’s receptors, being MOS the depending mainly on the type of product and the general health status main responsibles for this binding activity. Tiago et al. (30) showed of the animals. As reviewed by many authors, yeast products can affect both in vivo with mice and in vitro that selected strains of S. cerevisiae concentrations of platelets and WBC populations, phagocytic capacity were able to capture some enteropathogenic bacteria on the surface, of cells, secretion of pro- and anti-inflammatory cytokines, acute regardless of the yeast viability. However, this capturing ability was phase proteins concentrations, and antibodies production by binding limited to specific Gram-negative enteropathogens such as with complement receptor type three (CR3), dectin-1 or TLRs on Salmonella and Escherichia coli (E. coli). Mannan oligosaccharides different cells (16–18). Yeasts may also have an indirect effect on the form part of Saccharomyces cell walls, and their concentration is immune system through microbiota; as previously mentioned, especially high in yeast derivatives such as YCW. The mechanism β-glucans and MOS could increase Bifidobacterium population which, would be that mannose can occupy binding sites on fimbrial adhesins in return, has been shown to decrease the expression of toll-like on the surface of bacteria. This way, mannose residues in live yeast receptors (TLRs), NFkB, and cytokines, in vitro and in vivo with mice or derivatives could prevent certain bacteria that possess fimbria (19–21). Moreover, emerging studies also point out the potential of type-1 from adhering to the intestinal mucosa, thus avoiding yeast of altering the metabolism, including availability of glucose and colonization and multiplication to disease-causing levels (31–33). fatty acids, as another factor contributing to their capacity of modulate Saccharomyces cerevisiae var. boulardii has been widely used in the immune system (16). In conclusion, the immune response is a treating Clostridium difficile diarrhea and colitis. The mechanisms of complex process that goes beyond the response of a single immune this effect include increasing the activity of intestinal disaccharidases parameter; thus, to truly understand the mechanisms behind the (34) and stimulation of the intestinal secretion of s-IgA and of the possible beneficial effects of the use of yeast as an immunomodulator, secretory component of immunoglobulins (35, 36). Other authors integration of the different factors is needed. characterized a serine protease released by the yeast that hydrolyzes toxins A and B, which are C. difficile’s mediators of diarrhea and colitis, thus inhibiting the binding of the toxins to its intestinal 3.3. Increased digestibility receptor (37–39). More recent studies have found that S. boulardii exerts an effect on the structural component of the microbe’s biofilm Glucans present in yeasts could improve nutrient digestibility matrix in vitro, possibly affecting intestinal colonization (40). Reports through the modification of passage rate in the small intestine. This about the use of S. cerevisiae against this pathogen are scarce but effect would be mediated by the formation of a semisolid gel some demonstrate a protective effect of certain strains of the yeast in promoted by yeast’s alkali-soluble glucans that could slow the passage rats and mice (41, 42). Inhibition of other toxins such as cholera toxin and increase the time that the chyme is in contact with enzymes, or aflatoxin B1 has also been observed in in vitro and in vivo trials resulting in a higher digestibility of nutrients (22). As a result of this, using rats, with S. cerevisiae and S. boulardii, hypothesizing that in bacterial fermentation in the large intestine would be reduced as less this case the mode of action included binding of the toxin through a fermentable substrate would be available. However, one should receptor located in its surface (43, 44). be cautious with this hypothesis as in vivo studies with yeast β-glucans Saccharomyces cerevisiae was also able to reduce heat-labile have reported increases in apparent total tract digestibility (ATTD) enterotoxins production from Enterotoxigenic Escherichia coli in pre-ruminant calves (23) or no changes at all in dogs (24). Other (ETEC), associated with the removal of the toxin by the yeast and possible mechanism of yeast to modulate nutrient digestibility is the the reduction in the expression of its corresponding gene eltB (45). production of enzymes, such as amylases, lipases, and proteases. In the same series of assays, the yeast also interacted directly with Some studies with fish and hens have reported increases in digestive ETEC through agglutination in a mannose-related manner. enzymes with yeast supplementation, resulting in improved nutrients Lastly, S. cerevisiae-based probiotic has shown benefits in the digestibility (25, 26). treatment of bacterial vaginosis produced by Gardnerella vaginalis Despite this, other studies have reported decreases in crude protein in mice (46). In this case, the suggested mechanisms of action (CP), nitrogen-free extracts and dry matter (DM) apparent digestibility include direct interference with adherence to vaginal tissues, in dogs supplemented with MOS (27). These reductions in digestibility inhibition of sialidase activity and reduction of vaginal were accompanied by increased total fecal water and decreased unbound epithelial exfoliation. water which could mean different physical properties of intestinal chyme. Thus, the higher water binding could have had an impact on the solubility of nutrients and affected digestibility. 3.5. Antioxidant effect The activity of S. cerevisiae and derivatives has been assessed to 3.4. Protection against toxins and pathogens explore their potential as natural antioxidants, protecting cells against oxidative stress. Although it is probably a result of the Saccharomyces cerevisiae and other genetically close yeasts can combined action of different factors, cell wall β-glucans and exert a protective effect against toxins and pathogens through different mannans are thought to be the main actors in the antioxidant mechanisms that involve the binding of bacteria and toxins, capacity of yeasts. As widely review in the literature, these Frontiers in Veterinary Science 03 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 compounds can boost the antioxidant status of the body by skin diseases such as psoriasis or atopic dermatitis playing a pro- or improving the activity of antioxidant enzymes such as glutathione anti-inflammatory effect, but the exact mechanism has yet to peroxidase (GPx), catalase or superoxide dismutase (SOD) (17). be determined (66). Experiments with porcine jejunum epithelial cell lines damaged by deoxynivalenol, a strong inducer of oxidative stress, reported 3.6.2. Mood modulator promising results. The association of mannan and β-glucan from Probiotic ingestion has been linked to reduced anxiety-like yeast cell walls was able to down-regulate the production of behaviors via the hypothalamic–pituitary–adrenal axis and the malondialdehyde (MDA) and reactive oxygen species (ROS), while gut-brain axis (67). Supplementing a mixture of Bifidobacterium up-regulating the production of glutathione (47). In vivo studies lactis, Lactobacillus acidophilus, and Lactobacillus fermentum to with weaned piglets, supplemented with S. cerevisiae cell wall, also rats exposed to noise stress decreased behaviors related to anxiety resulted in decreased serum MDA and increased activity of the and also serum corticosterone (68). Saccharomyces sp. has also enzymes GPx, catalase and SOD (48). The addition of yeast been proven to attenuate anxiety-like behaviors in rats exposed β-glucans in broilers exposed to mycotoxins improved serum levels to LPS, possibly through modulation of the gut microbiota and of antioxidant enzymes and lower lipid peroxidation as well (49). hypothalamic–pituitary–adrenal axis (69). In this previous study, Moreover, the naturally good antioxidant capacities of selenium yeast supplementation led to significantly lower serum levels of seem to be improved by the enrichment with yeast, due to a synergic cortisol and corticosterone. Supplementation prevented the effect, as shown in in vitro and in vivo assays with mice (50). reduction in the serum levels of serotonin and brain-derived neurotrophic factor (downregulated during stress) in rats challenged with LPS, compared with those not supplemented and 3.6. Other effects challenged; however, the difference was not significant. Healthy medical students presented a decreased salivary serotonin 3.6.1. Skin health concentration when facing a stressful event after 30-day Saccharomyces cerevisiae extract, known occasionally as “skin supplementation with Saccharomyces sp., although an association respiratory factor,” has largely been used by humans for the treatment with anxiety, depression or eating attitudes was not found (70). of burns, wounds and hemorrhoids (51). Studies with human and Hemiplegic spastic cerebral palsy rats that exhibited depression animal models indicate that it accelerates healing stages: behavior improved their mental state when a Saccharomyces sp. inflammation, angiogenesis, granulation tissue and epithelial treatment was applied. This yeast increased gut microbiota migration (52–55). The active fraction of the extract has been diversity and decreased the level of inflammation and the identified as a mixture of peptides from 6 to 17 kD formed by: hypothalamic–pituitary–adrenal axis activity (71). In a study copper zinc superoxide-dismutase ubiquitin, glucose-lipid regulated with healthy human volunteers, subjects consuming the protein and acyl-CoA binding protein (51, 52). Gruenstein et al. (56) S. cerevisiae yeast hydrolysate showed better marks in used a human monocyte-derived cell line, THP-1, to study the questionnaires that assessed stress and anxiety, suggesting mechanisms involved in the extract and wound healing. These cells that this derivative could be effective in modulating are widely used to study monocyte functions and mechanisms, being behavior (72). monocytes one of the first immune cells to reach the wound site. Apparently, the yeast derivative activates phospholipase-C which results in an increase of cytoplasmic Ca2+. This in turn initiates the 4. Saccharomyces in dogs and cats transcription of early genes for tissue repair, such as c-fos. β-glucans are other components of the yeast cell wall that can have an effect on There are limited publications examining the impact of yeast or wound healing, facilitating the transportation of macrophages to the yeast by-products in the dog and cat, although the number is wound site, stimulating the tissue granulation and re-epithelization, increasing. This contrasts with livestock, where there are a wide and improving collagen deposition (57). number of publications on the use of yeast or yeast by-products. Topical application of S. cerevisiae has been shown to improve the Nevertheless, there is an ever-increasing demand for functional healing of burn wounds and to enhance the action of a collagen hydrogel- ingredients that improve companion animal health and yeast may scaffold, increasing epithelialization and biomechanical performance of prove to provide such benefits. wound area and reducing the scar size, in rats (58). Studies with Pets could benefit from the inclusion of yeast products in seabreams and trouts showed that feed supplementation with S. cerevisiae their diet, as some promising results have been described in the improved skin health and skin recovery from wounds (59, 60). scientific literature including the modulation of the intestinal The evidence of S. cerevisiae wound healing effect and its microbiota (with potential increases in Bifidobacterium or antioxidant properties have targeted the yeast as a potential Lactobacillus), enhancing of the immune function, reduction of biotechnological raw material in dermo-cosmetic formulations. potentially pathogenic microorganisms such as E. coli, Dermatological formulations that include S. cerevisiae extract or improvement of blood parameters related with obesity and derivatives showed positive effects in skin moisture and roughness in possible improvement in the antioxidant status, among others. In animal and human models (15, 57, 61); protection against UV the following sections we review some of the most recent irradiation both in vitro and in humans (62, 63) and itch relief in evidence on the potential benefits of using yeast or derivatives as chronic pruritus in humans (64, 65). functional ingredients in petfood. The main outputs of studies Saccharomyces cerevisiae has also been used as a skin cell model with live yeast S. cerevisiae and its by-products in dogs and cats in experimental biology. Lastly, this yeast has been linked to different are shown in Tables 2, 3, respectively. Frontiers in Veterinary Science 04 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 TABLE 2 Main outputs of different studies on the use of live yeast Saccharomyces cerevisiae and by-products in dogs. Product Dose Effects of the yeast product Ref. LY SC (strain CNCM I-5660; 0 (CON) or 0.12 (SUP) g daily of LY SC (1 Fecal microbiota: (5) Actisaf®; Phileo by Lesaffre) × 1010 CFU/g) for 49 days with abrupt ‑ ↓ Dysbiosis index, ↑ abundance of Bifidobacterium (days 35 and 49) and Turicibacter, and ↓ abundance of change of diet at day 22. Lactobacillus and E. coli. *Abrupt dietary change as challenge ‑ ↓ Firmicutes and ↑ Actinobacteria after the challenge. Hindgut fermentation products (fecal): ‑ ↓ Ammonia (day 23), ↓ total biogenic amines (days 21 and 49), and aromatic compounds. ↑ butyrate concentration. ‑ Others: ‑ CON showed upregulation in genes related to virulence factors, antibiotic resistance, and osmotic stress. LY SC (strain MUCL 39885; 0 (CON) or 7 × 1010 CFU SC/kg feed daily Digestion: (73) Biosprint®, Prosol S.p.A.) for 35 days (SUP) ‑ ↓ Fecal DM; the magnitude of the effect is questionable. ‑ =BW and feed intake. LY SC (strain CNCM I-4407; 0 (CON) or 2.9 × 108 CFU SC/kg BW Fecal microbiota: (74) Actisaf Sc 47; Phileo by (SUP) daily for 42 days ‑ ↓ E. coli and enterococci counts. Lesaffre) ‑ Digestion: ‑ ↑ Weight gain- ‑ ↑ ATTD of NDF, but not of the rest of nutrients. Different fermentation media 0 (CON), 10 g/kg food brewer’s yeast Fecal microbiota: (75) with SC (SUP1), 10 g/kg food brewer’s yeast + corn ‑ ↑ Bacteroides, Faecalibacterium, Phascolarctobacterium, Coprococcus. yeast (SUP2) and 10 g/kg food brewer’s Hindgut fermentation products (fecal): yeast + corn yeast + cell wall fractions ‑ ↑ Total SCFA, acetate and butyrate. (SUP3) for 20-day periods. ‑ ↓ Indole. Digestion: ‑ ↑ Preference. SCFP (TruMune, Diamond V 0 (CON) or 250 mg SCFP daily Fecal microbiota: (76) Mills, Inc.) (equivalent to approximately. 8.6 mg/kg ‑ After 21 days of supplementation, before the first exercise challenge, ↑ Clostridium in CON whereas not BW) (SUP) for 10 weeks change in SUP. Exercise challenge Others: ‑ For the rest of the parameters, exercise challenge was the primary cause of the shifts observed, but not the yeast. SCFP (TruMune, Diamond V 0 (CON) or 30 mg SCFP/kg BW (SUP) Digestion: (77) Mills, Inc.) daily for 11-weeks periods. - Change in fecal DM: ↓ (tendency) in CON but stable in SUP after transport. *Dogs challenged with transport stress Antioxidant properties: - Change in serum malondyaldehide ↑ and in serum 8-isoprostane ↑ (tendency), after transport, whereas in CON ↓. - No changes in the expression. Of genes associated with blood cyclooxygenase-2 and myeloperoxidase mRNA, after transport, whereas in CON ↑. SCFP (Diamond V Mills, Inc.) 0 (CON) or 30 mg SCFP/kg BW (SUP) Inmmunomodulation: (78) daily for 10-weeks periods. ‑ ↓ Changes in unstimulated lymphocytes and stimulated IFN-γ secreting T cells. ‑ ↓ Platelets; variable in CON. ‑ Variable basophils; ↑ in CON. ‑ Antioxidant properties: ‑ Change in serum superoxide dismutase concentration was ↑ and in catalase mRNA expression was ↓. Skin: ‑ ↑ (tendency) sebum concentration. ‑ ↑ Transepidermal water loss values in back region of CON and in ear region of SUP. SCFP (XPC™, Diamond V 0% (CON), 0.3% (SUP1), or 0.6% (SUP2) Fecal microbiota: (79) Mills, Inc.) SCFP of diet for 25-day periods. ‑ ↑ Actinobacteria and Firmicutes, and ↓ Fusobacteria. ‑ ↓ Allobaculum and Fusobacterium, and ↑ Clostridium. ‑ ↑ Collinsella and ↓ Prevotella in SUP2. Hindgut fermentation products (fecal): ‑ ↑ Propionate. Immunomodulation: ‑ ↑ phagocytosis index- Digestion: ‑ CF ATTD, ↓ CP and NFE ATTD, and ↓ ME in supplemented groups. SCFP (Diamond V Mills, Inc.) 0 (CON), 250 mg (SUP1) or 500 mg Immunomodulation: (80) (SUP2) daily for 14 weeks. ‑ ↑ TNF-α, ↓ IgE and IgG. * Dogs underwent exercise and transport ‑ ↑ Haptogoblin, serum amyloid A, and C-reactive protein stress Antioxidant properties: ‑ ↓ Thiobarbituric acid reactive substances, creatine kinase, and ↑ total antioxidant capacity. Others: ‑ ↑ Activity, running speed, and stool quality. (Continued) Frontiers in Veterinary Science 05 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 TABLE 2 (Continued) Product Dose Effects of the yeast product Ref. SCFP (Diamond V Mills, Inc.) 0 (CON), 125 (SUP1), 250 (SUP2), or 500 Fecal microbiota: (81) (SUP3) mg SCFP daily for 28-day periods - ↑ Actinobacteria, ↑ (tendency) Firmicutes, ↓ Fusobacteria. (12.1, 24.3, and 48.5 mg/kg BW) - ↑ Bifidobacterium, ↑ (tendency) Prevotella, and ↓ Fusobacterium. Sub-study: palatability test, 0.2% SCFP of Hindgut fermentation products (fecal): diet. ‑ ↓ Phenol and phenol+indoles, linearly with dosage. ‑ Immunomodulation: - ↓ WBC with increasing SCFP dose; SUP2 had ↓ WBC than CON. - ↑ MHC-II + B cell and monocyte expressing surface MHC-II populations. - ↓ TNF-α secretion from cells stimulated with TLR2, TLR3, TLR4 and TLR7/8 agonists. - ↑ IgE with dosage. - CON had the highest TNF-α concentrations. Digestion: - Slightly softer when comparing all SCFP treatments with CON. - TTD was not influenced. - ↑ Preference. Hydrolyzed SC (Progut®, 0% (CON) and 0.3% (SUP) hydrolyzed Fecal microbiota: (82) Suomen Rehu, patented SC of diet for 14 days (day 0 to day 14). ‑ ↑ Bifidobacterium (day 14 and day 42), lactic acid bacteria (day 42) and Clostridium (day 42). EP 1387620 hydrolysis process) Whole study 42 days. Hindgut fermentation products (fecal): ‑ ↑ pH (day 28). Obesity: ‑ ↓ Serum lipid profile (triglyceride, cholesterol) (day 42). Kidney and liver: ‑ ↑ ALT (day 14), AST (day 28 and 42), and urea serum levels. Hydrolyzed SC (Brewer’s Yeast, Control diet (CON) vs. control diet Digestion: (83) BY) substituted by 15% BY (SUP-BY), 7.5 and - ↓ Gross energy ATTD in ASCY and ISCY compared to CON. 15% autolyzed sugar cane (ASCY) or - ↓ Fecal DM with the addition of yeast. integral sugar cane (ISCY). 10 days. - ↑ Preference. Yeast extract (Nupro®, Alltech 0 (CON), 40, 80, or 120 g yeast extract/kg Hindgut fermentation products (fecal): (84) Brasil Ltda.) diet daily for 10-day periods - ↑ Total SCFA, propionate and butyrate with dosage. Sub-study: palatability test, 0 vs. 40 g yeast - ↓ Isovalerate and pH with dosage. extract/kg diet. Digestion: ‑ ↓ ATTD of CP and AHEE with dosage. ‑ ↑ Preference. YCW (Biolex MB 40, Leiber In vitro study, simulating the canine Fecal microbiota: (85) GmbH, Bramsche, Germany) gastrointestinal tract. Doses: 0 (CON), 0.5 - ↑ Bacteroidetes and ↓ Fusobacteria. (SUP1), 1.0 (SUP2) and 2.0 (SUP3) g/d - ↓ Enterobacteriaceae and Fusobacteriaceae. corresponding to 0.05, 0.1 and 0.2% in pet Hindgut fermentation products (fecal): food, for 3 weeks. - ↑ Gas production. - ↑ Acetate and butyrate. - ↑ Propionate for all SUP groups compared to CON in PC, but only for SUP3 in DC. - BCFA were low overall but significantly higher for SUP1 and SUP2 in both PC and DC, and only for SUP2 in DC. - ↑ Ammonia for SUP2 in PC and DC. YCW (Safmannan®, Phileo by 0 (CON) or 365 mg yeast daily (0.2% of Fecal microbiota: (86) Lesaffre) diet) (SUP) for 28-day periods with an ‑ ↑ (tendency) C. perfringens. abrupt diet transition at day 15 Immunomodulation: *Abrupt dietary change as a challenge. ‑ ↑ (tendency) fecal IgA, after abrupt diet transition. Conventional YCW and 0 (CON), 0.3% YCW (SUP1) and 0.3% Hindgut fermentation products (fecal): (87) specific high solubility of MOS YCWs (SUP2) of the diet for 32-day - ↑ Butyrate and ↓ lactate in SUP2. YCW (YCWs) (Biorigin, periods - ↑ Putrescine and ↑ (tendency) spermidine in SUP2. Brazil) Immunomodulation: - ↓ Serum IL-6 in SUP2. - ↓ (tendency) serum IL-6 and TNF-α in SUP1. - ↑ Phagocytic index in peripheral monocytes. Digestion: ‑ ↓ AHEE ATTD in SUP2. YCW (DMB; Bio-Mos, Alltech 0 (CON) and 1.4% YCW (SUP) of the diet Fecal microbiota: (88) Nicholasville, KY) for 21-day periods ‑ ↑ Bifidobacterium and ↓ Clostridium celerecrescens. *Raw diets: beef and chicken. YCW (DMB; Bio-Mos, Alltech 0 (CON) and 1.4% YCW (SUP) of the diet Hindgut fermentation products (fecal): (89) Nicholasville, KY) for 21-day periods - When used in the chicken diet: ↓ pH, ↓ indole and ↑ spermine. *Raw diets: beef and chicken. - When used in the beef diet: ↑ fecal acetate, total SCFA, and spermine. Digestion: ‑ When used in the beef diet: ↑ (tendency) fecal output and softer feces.↓ DM, OM, CP and energy ATTD. (Continued) Frontiers in Veterinary Science 06 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 TABLE 2 (Continued) Product Dose Effects of the yeast product Ref. YCW (Safmannan®, Phileo by 0 (CON), 0.07 (SUP1), 0.35 (SUP2) or Fecal microbiota: (90) Lesaffre) 0.91 (SUP3) g of YCW per animal twice ‑ ↓ E. coli. Clostridium perfringens responded cubically to supplementation. daily for 14-day periods. Immunomodulation: Doses correspond to 0, 0.05, 0.25, 0.45, or - ↓ (tendency) quadratically of WBC and eosinophils, and ↓ linearly of monocyte with dosage. 0.65% of food offered. - Serum IgA responded cubically to supplementation whereas ileal IgA tended to respond quadratically, with the greatest value in SUP2. Digestion: - ↑ (tendency) apparent Ileal digestibility of DM, OM, CP, and GE. - ATTD of DM, OM, CP, AHEE, and GE responded cubically to supplementation, being lowest in SUP2. Yeast-derived MOS, high in 0 (CON), 400 mg (SUP1), or 800 mg Immunomodulation: (91) mannoproteins (Actigen, MOS/kg (SUP2) of diet daily for 28 days, ‑ ↑ (tendency) neutrophil phagocytic activity in SUP1 compared with SUP2. Alltech Inc.) *Use of adult and elderly dogs Antioxidant properties: ‑ ↑ (tendency) production of H2O2 when neutrophils were stimulated with LPS. Skin: ‑ Diet influenced the delayed cutaneous hypersensitivity test upon saline inoculation. Yeast-derived MOS (Provimi 0 (CON) or 15 g MOS/kg of diet (SUP) for Immunomodulation: (92) Animal Nutrition) 150 days. ‑ ↑ Cell-mediated immune response, CD4+ lymphocyte population and CD4+:CD8+ ratio. Obesity: ‑ ↓ Serum total- and LDL- cholesterol. Yeast-derived MOS (Bio-MOS, 0 (CON) or 2 g/kg BW (SUP) daily for Management of gastrointestinal disorders: (93) Alltech Inc.) 20 days from 24 h after infection. ‑ Faster recovery from infection. *Challenge with enteropathogenic Escherichia coli Yeast-derived MOS 0 (CON), 1% dietary chicory (SUP1), 1% Fecal microbiota: (94) dietary MOS (SUP2) or 1% chicory +1% - ↑ Bifidobacterium in SUP1 and SUP2. MOS (SUP3) for 28 days. - ↓ E.coli in SUP2 Immunomodulation: - ↓ (tendency) lymphocytes in SUP2 and SUP3. - ↑ (tendency) neutrophils in SUP1 and SUP3. Digestion: - ↑ (tendency) feed intake in SUP2 and SUP3. - ↑ Fecal score in SUP3, although still in desirable range. Yeast-derived MOS (Bio-MOS, 0 FOS/MOS (CON), 1 g FOS (SUP1), 1 g Fecal microbiota: (95) Alltech Inc.) MOS (SUP2), 1 g FOS + 1 g MOS (SUP3) - ↓ Total aerobes in SUP2. twice daily for 14-day periods - ↓ (tendency) total anaerobes in SUP3. Hindgut fermentation products (fecal): - ↓ Phenols + indoles, and ↓ (tendency) indoles in SUP1 and SUP3. - ↑ (tendency) pH in SUP2. Immunomodulation: - ↑ Ileal IgA in SUP3. - ↑ lymphocytes in SUP2. Yeast-derived MOS (Bio-MOS, 0 (CON) vs. 1 g/kg BW (SUP) daily for Hindgut fermentation products (fecal): (27) Alltech Inc.) 10 days (5% of diet) - ↓ Unbound water, fecal pH, and ammonia. Digestion: - ↓ ATTD ofCP, DM and nitrogen-free extracts. ↑ ATTD of CF. Yeast-derived MOS (DP607, 0 (CON) vs. 5 g/kg of diet DM (SUP) daily Hindgut fermentation products (fecal): (96) Alltech Inc.) for 21-day periods. - ↑ (tendency) ileal butyrate in CON. Digestion: - ↓ (tendency) amount of feces excreted on a DM in CON. Concentrated BY (not 0 (CON) vs. 7 mg/kg BW of β-glucan Hindgut fermentation products (fecal): (97) specified, possibly β-glucans) (SUP) daily for 10 weeks. - ↑ Arabinose. (F.L. Emmert Company, USA). Immunomodulation: - ↓ (tendency) gut permeability. - ↓ Serum haptoglobin levels. Yeast-derived β-glucan 0 (CON) vs. 0.1% (SUP) of diet, for Obesity: (98) 90 days, in obese dogs. - ↓ Plasma glucose triglyceride, and cholesterol concentrations. - ↑ GLP-1. Immunomodulation: - ↓ TNF-α. Yeast-derived β-glucan 0 (CON), 0.012 (SUP1) and 0.023% - No effect of the β-glucan in the analyzed parameters. (24) (Wellmune for Pet™, Kerry (SUP2) of diet for 28 days. Incorporated, Beloit, WI) (Continued) Frontiers in Veterinary Science 07 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 TABLE 2 (Continued) Product Dose Effects of the yeast product Ref. Yeast-derived β-glucan 0 (CON), 150 ppm β-glucan top-dressed Digestion: (99) (SUP1), 150 ppm retorted β-glucan - ↑ ATTD of DM, CP and GEin SUP2. ATTD of GE was greater for SUP2 than for both CON and SUP1. included in diet formulation (SUP2), during 42 d. Vaccine challenge Yeast-derived β-glucan (BG01 0 (CON), 15 mg/kg/day of BG01 (SUP1) Immunomodulation: (100) and BG02, Biorigin) or 25 mg/kg/day of BG02 (SUP2) - ↑ Phagocytic activity of blood monocytes and neutrophils. - ↑ IL-2 and anti-ovalbumin antibodies production (antibody response). - ↓ Blood glucose in dogs with hyperglycemia. Yeast-derived β-glucan (Biolex- 0 (CON) vs. 7 mg/kg BW (SUP) daily for Immunomodulation: (101) Beta HP. Inter Yeast Poland). 6 weeks - ↓ IL6 and ↑ IL-10. *Dogs with IBD Management of gastrointestinal disorders: - Most efficient treatment efficacy by producing the quickest therapeutic effect. - No recurrence of IBD at least for 6 months after the experiment. Yeast-derived β-glucan 0 (CON) vs. 800 ppm of β-glucan (SUP) Immunomodulation: (102) (MacroGuard, Biorigin) daily for 8 weeks. - Numerical improvement in the scores of itching, redness, scaling, thickening, and stripping of skin, but *Dogs with atopic dermatitis signs notstatistical significance compared with CON. - Global improvement (sum of all the parameters) of the atopy index was 63% comparing SUP with CON. - ↑ Coat quality. Yeast-derived β-glucan 0 (CON) vs. 800 ppm of β-glucan (SUP) Immunomodulation: (103) (MacroGuard, Biorigin) daily for 8 weeks. - Numerical improvement in the scores of activity, stiffness, swelling of joing, lameness, and pain, but the *Dogs with osteoarthritis signs differences between CON and SUP did not reach statistical significance. Yeast-derived β-glucan 0 (CON) vs. 225 mg of β-glucan (SUP) Immunomodulation: (104) (MacroGuard, Biorigin) daily for 4 weeks. Experiment 1: Experiment 1. No vaccine. - ↓ IgA and ↑ IgM serum concentrations. Experiment 2. Vaccine challenge - ↑ - ↓ Saliva and tears IgA. Increase of saliva IgA after the end of the supplementation was also higher for SUP group. Experiment 2: - After vaccination, antigen-specific IgM increased similarly to total IgM. - Antigen-specific IgA remained nearly unchanged, whereas it was increased in CON. Dried yeast Different diets with different primary Fecal microbiota: (105) protein source: poultry by-product meal - ↑ β-diversity in SUP1. (CON), dried yeast product (SUP1, 30% - ↑ Several genera belonging to Firmicutes. of the diet), garbanzo beans (SUP2), green Hindgut fermentation products (fecal): lentils (SUP3) and peanut flour (SUP4), - ↑ Acetate, butyrate and total SCFA. for 14-day periods - ↑ Valerate. - ↓ Phenols and total phenol/indoles. Digestion: - ↓ DM, OM and AHEE ATTD, although still >80%. ↓ Metabolizable energy content. - ↑ Fecal output. Dried yeast 0 (CON) or 0.19 g/kg BW (SUP) daily for Obesity: (106) 28–63 days - Removal of the yeast in hyperthyroid dogs resulted in lower intake and anorexia. *This study is about hyperthyroidism, B1 deficiency and yeast supplementation. AHEE, acid-hydrolized ether extract; ALT, alanine transaminase; AST, aspartate transferase; ATTD, apparent total tract digestibility; BCFA, branched-chain fatty acids; BW, body weight; CF, crude fiber; CFU, colony forming units; CP, crude protein; CON, control group; DC, distal colon; DM, dry matter; GE, gross energy; IBD, intestinal bowel disease; IFN, interferon; Ig, immunoglobulin; IL, interleukin; LY, live yeast; MHC, major histocompatibility complex; MOS, mannan oligosaccharides; NFE, nitrogen-free extract; NDF, neutral detergent fiber; ME, metabolizable energy; OM, organic matter; PC, proximal colon; Ref., reference; SC, Saccharomyces cerevisiae; SCFA, short-chain fatty acids; SCFP, Saccharomyces cerevisiae fermentation product; SUP, supplemented group; TLR, toll like receptor; TNF, tumor necrosis factor; YCW, yeast cell wall; WBC, white blood cells. 4.1. Modulation of gut microbiota and At the genus level, Bifidobacterium increased with live yeast, SCFP, hindgut fermentation yeast hydrolysate, or MOS addition (5, 81, 82, 88, 94). Prevotella relative abundance increased while Fusobacterium decreased with The addition of yeast by-products in dogs’ diet produces changes higher doses of SCFP supplementation (81). Santos et al. (79) also in gut’s bacterial population. Supplementation with SCFP has resulted observed reduced Fusobacterium and Allobaculum, as well as in increases in the relative abundance of the phyla Firmicutes and/or increased Clostridium with the inclusion of SCFP; in this same study, Actinobacteria, and decreases of Fusobacteria (79, 81). Accordingly, a level of 0.6% SCFP of the diet resulted in a decrease of Prevotella and use of dried yeast as primary protein source in a dog diet resulted in an increase of genus Collinsella. Increases in genera considered higher relative abundances of several genera belonging to Firmicutes beneficial and related with the production of SCFA, such as phylum (105). An in vivo study simulating the canine intestinal Bacteroides, Faecalibacterium, Coprococcus, and Phascolarctobacterium, microbial ecosystem also reported a decrease in Fusobacteria and an were reported with the use of yeast products (75). Fecal Lactobacillus increase in Bacteroidetes with the addition of YCW (85). tended to be higher and total aerobes tended to be lower in dogs Frontiers in Veterinary Science 08 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 TABLE 3 Main outputs of different studies on the use of live yeast Saccharomyces cerevisiae and by-products in cats. Product Dose Results Ref. LY SC (strain MUCL 39885; 0 (CON) or 7.5 × 10 CFU SC/kg feed daily for 35 days 10 Digestion: (73) Biosprint®, Prosol S.p.A.) (SUP) - ↑ Fecal DM (day 28). SCFP (XPC™, Diamond V) 0% (CON), 0.3% (SUP1) or 0.6% (SUP2) SCFP of diet Fecal microbiota: (107) for 25-day periods - ↓ Clostridium perfringens. Hindgut fermentation products (fecal): - ↑ Lactic acid. - ↓ Isovaleric in SUP1. Digestion: - ↑ ATTD of CF and ash. - ↓ GE in SUP2. Yeast extract (Nupro®, Alltech Exp. 1: 0% (CON) vs. 30% replacement by yeast extract Exp. 1: yeast extract as an ingredient: (108) Brasil Ltda.) (SUP). 10-day periods. - According to ATTD, yeast extract is comparable to other protein Exp. 2: 0% (CON) vs. 2% (SUP1), 4% (SUP2), 6% sources. (SUP3), 8% (SUP4) and 10% (SUP5) replacement. Exp. 2: yeast extract as a functional additive: 15-day periods. - No changes. Exp. 3: 0% vs. 2% replacement with yeast extract. 4 days. Exp. 3: yeast extract as a palatability agent: - Preference for control diet was observed. Yeast extract (Nupro®, Alltech 0% (CON), 0.6% phosphoric acid (SUP1), 1.5% yeast Digestion: (109) Brasil Ltda.) extract (SUP2), combination of A + Y (SUP3) for 15-day - ↑ ATTD of DM and ashes in SUP3. period. - ↓ DM intake in SUP1 and SUP2. Yeast extract 0 (CON), 0.2 (SUP1), 0.4 (SUP2) or 0.6% (SUP3) yeast - Changes on the intestinal mucosa in SUP3 were noticed, related (110) extract in wet food with an inflammatory response. YCW Exp. 1: 0 (CON), 0.2 (SUP1), 0.4 (SUP2) or 0.6% (SUP3) Exp. 1: no changes. (111) YCW in wet food, for 30 days. Exp. 2: ↑ ATTD of DM, linearly with dosage. Exp. 2 (25 days): 0 (CON), 0.2 (SUP1), 0.4 (SUP2) or Exp. 3: ↓ preference. 0.6% (SUP3) YCW in dry food, for 25 days. Exp. 3: 0 and 0.4% YCW in wet food for 10 days. Yeast-derived MOS (Bio-MOS, 0% (CON), 0.2% (SUP1) 0.4% (SUP2) and 0.6% (SUP) Fecal microbiota: (112) Alltech Inc.) inclusion of YCW for 34-day periods - ↓ Clostridium perfringens (linear) and Escherichia coli (quadratic). - ↑ Bifidobacterium and Lactobacillus with dosage. Hindgut fermentation products (fecal): - ↑ Butyrate, valerate, total biogenic amines, putrescine, cadaverine and histamine increased with dosage. Digestion: - ↑ Ash ATTD of ash. Increased with YCW content. AHEE, acid-hydrolyzed ether extract; ATTD, apparent total tract digestibility; BW, body weight; CF, crude fiber; CFU, colony forming units; CON, control group; CP, crude protein; DM, dry matter; GE, gross energy; LY, live yeast; OM, organic matter; Ref., reference; SC, Saccharomyces cerevisiae; SCFA, short-chain fatty acids; SUP, supplemented group; YCW, yeast cell wall. supplemented with MOS whereas supplementation with both FOS concentrations of SCFA have been reported when yeast or yeast and MOS resulted in a tendency of lower total anaerobe concentration by-products were used (24, 74, 81, 95, 97). However, decreases in compared with control (95), although no impact on Bifidobacterium isovalerate and/or increases in propionate, butyrate, acetate and total was noted in this case. SCFA when using yeast products have been reported by different Increases in Lactobacillus and Bifidobacterium would likely yield authors (5, 75, 81, 95). Van den Abbeele et al. (85) also observed increased lactic acid and short-chain fatty acids (SCFA), which could increases in acetate, butyrate and propionate when adding YCW in be the reason behind the lower fecal pH observed by some authors their in vitro experiment simulating the canine gut. Moreover, after the inclusion of yeast derivatives in dogs’ diets along with concentration of fecal phenol and/or total phenol + indole were lower decreased fecal ammonia (27, 84). Bastos et al. (5) also observed lower in dogs supplemented with yeast products (5, 75, 81, 95). Total fecal fecal ammonia levels after an abrupt dietary change in dogs biogenic amines decreased significantly in dogs receiving live yeast (5) supplemented with live yeast compared to control ones. However, (5). These results may indicate the possible beneficial effects of yeast these finding have not been consistent as other authors have reported and yeast by-products on the canine intestinal functionality. higher fecal pH (82, 90, 95) or no change (24, 74, 81, 86). Yeast cell wall supplementation in cats also led to increased fecal Short chain fatty acids are rapidly absorbed by colonocytes, thus Bifidobacterium and Lactobacillus, and reductions of Clostridium determining their levels in vivo can be challenging, perhaps perfringens (C. perfringens), E. coli, Hafnia alvei, and Shigella spp. contributing to the varying results reported. Unaltered fecal (112). The inclusion of SCFP in cats’ diet reduced C. perfringens Frontiers in Veterinary Science 09 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 abundance, however no change for Bifidobacterium, Lactobacillus, or dogs supplemented with MOS. In contrast, Kroll et al. (91), did not E. coli was observed (107). Supplementation with a microencapsulation observe changes in those cell communities when supplementing adult of probiotic strains which include S. cerevisiae for 20 days resulted in or senior dogs a second-generation MOS, rich in mannoproteins. fecal Lactobacillus count increase, but the effect of yeast cannot Studies with dogs involving stress challenges suggest some benefits be isolated in this study (113). Aquino et al. (110) did not find related to the modulation of the immune system as well. Dogs differences in lactic acid bacteria counts nor clostridium-reductor supplemented with SCFP and challenged with exercise and transport when substituting up to 0.6% of the wet diet with yeast extract in cats. stress had increased serum TNF-α and decreased IgE and IgG, although There were no differences in cats’ fecal pH when SCFP or yeast the vitality of these animals was higher (80). In another study involving extract was supplemented (107, 109). Matheus et al. (107) compared transport stress challenge, SCFP addition caused stable or decreased a control diet without SCFP with two different inclusion levels (0.3 cyclooxygenase-2 and myeloperoxidase mRNA expression, two key and 0.6% of the diet), and failed to find differences in fecal pH, inflammatory mediators. These findings suggest a positive impact ammonia, or SCFA between treatments (except for isovaleric acid, through suppression of innate immune cell activation against stress. which was lower in 0.3% SCFP inclusion group), However they did The supplementation of β-glucans derived from S. cerevisiae also report higher fecal lactic acid concentration in cats supplemented with influenced the humoral immune response to vaccination, affecting SCFP compared with control ones. On the other hand, lactic acid was IgA and IgM responses (104), whereas Traughber et al. (99) did not not changed and neither propionate, isovalerate, acetate, isobutyrate, observe any effect. total SCFA, and total BCFA when YCW was included in the feed at The modulatory effect of yeasts in the immune system is especially 0.2, 0.4, or 0.6% of the diet (112). These last authors also found that relevant in the treatment of some inflammatory diseases; in fact, the fecal concentrations of cadaverine, histamine, putrescine, and total β-glucan was superior to levamisole in the treatment of dogs affected biogenic amines increased linearly with the inclusion of by Inflammatory Bowel Disease (IBD) (101) and had promising YCW. Collectively, these studies present a lack of consistent responses results treating dogs with signs of canine atopy and osteoarthritis to yeast or yeast derivatives, which may suggest strain specific impact, (102, 103). but that too will require additional assessments. Hematological changes due to yeast supplementation, similar to other parameters, vary greatly among the studies. Some studies have found an increase within the reference ranges in mean corpuscular 4.2. Immunomodulatory properties volume and mean corpuscular hemoglobin concentration and no effect on white blood cells (WBC) counts in dogs fed live yeast (74). Immunity is certainly an area of interest for functional Others noted a decrease in WBC, monocyte and eosinophils counts ingredients and may be positively influenced by yeast intake, at least in dogs given SCFP or YCW components (81, 90). Although these last in dogs. Supplementation of dogs with YCW, alone or in combination authors did not find differences in lymphocyte counts, others found with FOS, resulted in increased ileal and fecal IgA (86, 90, 95), an increase (95) and a decrease (78, 94) when supplementing yeast indicating enhanced mucosal immunity. Some of these authors also derivatives to dogs. found serum IgA increases of around 20% compared with control Although the number of studies evaluating immune modulation when including YCW at 0.45–0.5% of the diet. Lin et al. (81), on the in dogs is limited, even less is known regarding to cat. Matheus et al. other hand, did not find differences in serum IgA, IgE, IgG, and IgM (107) did not report any difference in cats supplemented with SCFP when supplementing SCFP compared to control, but higher SCFP when comparing CD4+ or CD8+ lymphocytes, CD4+/CD8+ ratio, or dosages led to higher IgE concentrations. However, these latter phagocytosis index, among other parameters involved in immune authors found that dogs supplemented with SCFP had increased response which also did not change. Hematological changes were population of antigen-presenting cells, including B-cells and neither observed when yeast extract was supplemented up to 10% in monocytes expressing surface major histocompatibility complex the diet for cats (108). class II. One hypothesis would be that fewer immune cells are needed when immune capacity is enhanced. Moreover, in the same study cells obtained from dogs supplemented with SCFP had a lower 4.3. Inhibition of pathogens and TNF-α secretion when stimulated with toll-like receptor (TLR) management of gastrointestinal disorders agonists compared to control dogs, suggesting an anti-inflammatory effect of SCFP. Accordingly, lower pro-inflammatory interleukin 6 As previously discussed, supplementation of yeast and its (IL-6) and TNF-α, as well as higher blood monocyte phagocytic derivatives can modulate gut microbiota, providing possible benefits. index, were shown by dogs receiving YCW in the study by Theodoro This subsection will go through the changes in potentially pathogenic et al. (87). This increased phagocytic index was also observed with microorganisms that also inhabit the gastrointestinal tract, and the the inclusion of SCFP (79), althought others authors did not report role that yeast can have in the management of some any changes with yeast hydrolysate supplementation (82). The gastrointestinal disorders. ingestion of yeast-derived β-glucan also produced lower levels of Although E. coli can sometimes have a positive effect in the gut, TNF-α in obese dogs (98), as well as lower serum concentrations of such as stimulation of the immune system or vitamin K production, IL-6, increased anti-inflammatory IL-10, reduced haptoglobin its proliferation is more often associated with a negative impact. In this (marker of inflammatory status), and tended to reduce gut regard, the supplementation of live yeast, autolyzed YCW and MOS permeability (97, 101). from S. cerevisiae has resulted in lower counts of E. coli (5, 74, 90, 94), Pawar et al. (92) found an enhanced cell-mediated immune although some other authors have not found differences with addition response, CD4+ lymphocyte population and CD4+:CD8+ ratio in of MOS, FOS, or the combination of both (95). Even in an in vitro Frontiers in Veterinary Science 10 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 experiment simulating the canine gut, adding YCW decreased the difference was very limited. Increases in intake ratio for diets presence of the Enterobacteriaceae family, which includes E. coli (85). containing yeast products when compared to diets without yeast Another potentially harmful bacteria that could be modulated by yeast have also been reported, although they were not accompanied by is C. perfringens. Whereas some authors did not find differences with differences in dry matter intake or body weight increase (83, 84). MOS supplementation (95), other studies have reported higher Lastly, a study involving dogs with hyperthyroidism showed that C. perfringens counts with yeast extract supplementation but neither the cessation of yeast as a vitamin B1 source in hypothyroid dogs was accompanied by diarrhea (86, 90). However, Oba et al. (76) resulted in loss of appetite and anorexia (106). observed that C. perfringens abundance increased in control dogs and was stable for dogs fed SCFP for 21 days. Similarly, decreases in other species of Clostridium such as Clostridium celerecrescens and 4.5. Effects on digestion Clostridium saccharolyticum were observed in dogs fed YCW (88, 89). Bastos et al. (5) reported that control dogs, compared with dogs Regarding the potential effect of yeast on digestive function and receiving a live yeast supplementation, showed upregulation in genes digestibility of nutrients, results in the literature are variable and related to virulence factors, antibiotic resistance, and osmotic stress. sometimes contradictory, although the most common findings are The use of S. boulardii in dogs with gastrointestinal disorders decreases in CP ATTD and occasionally increases in fiber ATTD. has also been studied, with promising results. One publication Live yeast supplementation had no significant effect on DM, ash, focused on the use of this yeast as a probiotic in dogs with crude fiber (CF), CP and fat ATTD (5); only non-digestible fiber diarrhea induced by lincomycin (114). Twenty-four dogs were ATTD was higher in supplemented dogs (74). Santos et al. (79) also given lincomycin intramuscularly (150 mg/kg BW/d) and three found increased ATTD of crude fiber when SCFP was added, but groups were formed (n = 8): (I) no S. boulardii, (II) S. boulardii decreased ATTD of CP, nitrogen-free extract and metabolizable energy. (1,000 mg/d orally for 10 days) after lincomycin induced diarrhea On the other hand, Middelbos et al. (90) tried different doses of onset, and (III) S. boulardii (1,000 mg/d orally for 10 days) YCW inclusion on the diet (from 0 to 0.65% of the diet, mostly MOS) together with lincomycin. The results showed that groups I and and reported increases in DM, organic matter (OM), CP, and gross II had diarrhea and lower fecal SCFA concentrations, but not energy (GE) ileal digestibility compared to control animals but decreases group III, and the duration of this gastrointestinal alteration was in DM and CP ATTD. Similarly, YCW included as 1.4% of the diet shorter in group II compared to control. Another publication resulted in reduced ATTD of DM, OM, CP, fat, and GE (89) and MOS used S. boulardii in dogs with chronic enteropathy (CE) (115). as 5% of the diet reduced ATTD of DM, CP and nitrogen-free extracts Four healthy dogs and 20 dogs with CE were used and S. boulardii (27). Addition of yeast extract or dried yeast also lowered ATTD of was administered at a dose of 1 × 109 CFU/kg BW orally in different macronutrients (84, 105). Protein excretion may result from capsules every 12 h. In healthy dogs, the administration of increased bacterial growth and excretion due to increased fermentation, S. boulardii for 10 days reached a steady state in 5 days and was underestimating CP digestibility and, in turn, lowering OM and DM eliminated completely 4 days after administration, without side digestibility. However, other studies with various kinds of yeast products effects. Dogs with CE received placebo or S. boulardii for 60 days: (MOS, β-glucans, SCFP and SC from Brewer’s yeast) did not find the yeast significantly improved clinical activity index, stool significant differences neither in ileal nor in apparent total tract nutrient frequency, and consistency and body condition score over digestibilities when compared to control diet (24, 75, 81, 83, 92, 94–96). control dogs. Fecal score was higher (wetter feces) in some studies Lastly, yeast cell wall could also have a positive impact in supplementing SCFP, YCW or MOS to dogs when compared to recovering gut health. Dogs fed MOS and experimentally infected control groups, although the values remained within the ideal score with different strains of enteropathogenic E. coli recovered faster than range (81, 89). Martins et al. (83) observed that dietary yeast inclusion control ones, indicating an improvement in the defense system of the of 30% of the diet resulted in diarrhea and soft feces but an inclusion animals (93). On the other hand, yeast-derived β-glucan were superior of up to 15% was suitable, without changes in fecal consistency. against levamisole in the treatment of dogs affected by IBD, achieving However, the inclusion of a live SC yeast as in 7 × 1010 CFU/kg feed a fast recovery with no recurrence, at least in 6 months (101). resulted in significant higher fecal dry matter, although the magnitude of the changes was of questionable biological relevance (73). Nevertheless, many of the other studies mentioned in this section did 4.4. Management of obesity not find any differences in fecal score with the dietary inclusion of yeast products generally up to 5% of the diet, with the exception of the Components of yeasts such as β-glucan could play a role in obesity 12% inclusion of yeast extract in Kaelle et al. (84). prevention and treatment, as obese dogs fed yeast-derived β-glucan As for cats, regarding digestibility, there were no differences in had lower plasma basal glycemic values, serum cholesterol and nutrient and energy utilization when yeast extract was included in triglyceride levels (98). Reduced serum total- and LDL-cholesterol the feed up to 10% in the diet (108) or when yeast extract was added concentration was also reported in dogs supplemented with MOS (92) without an acidifying agent (109). Matheus et al. (107) also found and β-glucans (97, 98) from SC. relatively similar results, except for CF and ash digestibility, which However, the potential effect of yeast on weight is not clear. were higher with SCFP inclusion, although the authors recommend Several studies reported no effect on feed intake or body weight taking these results with cautions as they warn that there may (BW) in dogs (24, 73, 81, 86, 90, 97, 105). However, Stercova et al. be calculation errors due to low fiber concentration of the diets. Yeast (74) observed that dogs fed capsulated live yeast SC showed a cell wall inclusion also resulted in improved DM and ash digestibility higher increase of BW compared with the control ones, but the in cats (112). Frontiers in Veterinary Science 11 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 4.6. Kidney and liver health nucleotides, which can intensify flavors of the food (75, 81, 84). These results indicate that yeast or yeast by-products are well Dogs kidney and liver function assessed through serum urea, accepted by dogs, so their inclusion in commercial diets would creatinine, alkaline phosphatase (ALP), and alanine transaminase not cause refusal and thereby negatively affect the food intake (ALT) seems to be unaltered in some studies where dogs were and body condition. supplemented with live yeast or yeast by-products (74, 81). However, Regarding S. boulardii, there is one publication about the the activity of ALT and aspartate aminotransferase (ASP) was production of meat pet snacks containing this yeast that studied the increased in dogs supplemented with yeast hydrolysate during and production process, viability and acceptability of the snacks, showing after 28 days of supplementation (82). This same study showed that the addition of yeast had a good acceptance (116). increased serum urea levels in dogs receiving the hydrolysate in the Contrary to dogs, in which the use of live yeast or derivatives post-treatment period whereas total protein, albumin, glucose, and seemed to increase palatability, results in cats are not uniform ALP did not change significantly. and tend to show worse palatability with yeast supplementation. No difference in feed intake compared to control group was found when evaluating the use of live yeast, SCFP or YCW (73, 4.7. Potential antioxidant properties 107, 112). On the other hand, Lima et al. (108) evaluated the use of yeast Very few studies have assessed the effect of S. cerevisiae on extract as a palatability agent observing that cats preferred the the oxidative status of dogs, although some positive results have control diet over 2% inclusion yeast diet. Similar to Lima, Ogoshi been obtained. Supplementation with SCFP at a dose of 500 mg/ et al. (109) found that the inclusion of yeast extract at 1.5% of the day decreased thioboarbituric acid reactive substance and diet reduced feed consumption. Aquino et al. (111) reported increased total antioxidant capacity in serum of dogs exposed to lower palatability with wet diets that contained a 0.4% of exercise and transport stress, which could indicate an enhanced YCW. Lower preference for yeast extract seems to be countered protection against oxidative damage (80). Wilson et al. (78) also with the addition of sodium pyrophosphate; this blend was more measured markers and expression of genes related to oxidative preferred than control (117). Excess of umami taste and stress in dogs fed SCFP compared to control ones and observed monosodium glutamate could reduce palatability and cats could that superoxide dismutase enzyme increased from baseline and have a lower threshold of acceptance. Moreover, processing may mRNA expression of catalase was lower. However, more affect the flavor profile so thermal processes can decrease the investigation is necessary as another study of the same authors flavor-enhancing effect and increase the acceptance of the showed that SCFP-fed dogs increased malondialdehyde and ingredient. It is also hypothesized that the rejection of yeast 8-isoprostane levels due to transport stress (77). Lastly, the extract is due to its high content in leucine as cats reject amino supplementation of MOS or SCFP (125, 250, and 500 mg/day) did acids “bitter” for humans such as this one. not exert any effect on erythrocytic antioxidant indices when compared to the non-supplemented group (81, 92). 5. Concluding remarks and future perspectives 4.8. Skin and hair Pet humanization has led to an increase in the demand for To the knowledge of the authors, only two studies have functional ingredients in the pet food industry. Owners are more investigated the effects of S. cerevisiae supplementation on skin concerned about pet health and wellness and are willing to invest and hair health of dogs. A tendency for higher change from in diets with superior properties even if it means that they are baseline in sebum concentrations was observed in dogs fed SCFP more expensive, as long as their dogs and cats are healthier. The that did not result in greasy hair coat (78). In this study, higher wide range of yeast-based products with potential to be used as Transepidermal Water Loss (TEWL) in the ear region was also prebiotic, probiotic, or postbiotic is of great interest at present, as measured in supplemented dogs, possibly indicating enhanced they are becoming more related to the successful treatment of skin integrity. However, TEWL in the back region was higher in diseases. Based on the fact that the main scientific knowledge is control dogs but the authors of the study warn that this may gathered from human and livestock studies, further investigations be due to alterations during sampling. In fact, Beloshapka et al. are still required in pet species to better understand the mode of (88) found no difference in the skin condition score in the tail action, doses, safety, and guidelines for use of these products. region or any other skin and coat scores when dogs were While the gut will probably remain the heartland of research, new supplemented with YCW. clinical applications will continue to expand in other research areas including immune system, skin, nervous system, oral cavity, kidney, respiratory system, and weight management field. Thanks to 4.9. Impact on palatability significant and accelerating advances in biotechnologies and bioinformatics methodologies, new research will better characterize Palatability tests comparing standard diets with diets mechanistic insights into the mode of action of yeast and their including yeast products have resulted in a preference for the derivatives, leading to a more targeted-oriented development of latter, probably due to the presence of glutamic acid and S. cerevisiae-based products. Frontiers in Veterinary Science 12 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 Author contributions Conflict of interest MM: Methodology, Writing – review & editing. LC: Methodology, The authors declare that the research was conducted in the Writing – review & editing, Supervision. SM-O: Methodology, absence of any commercial or financial relationships that could Supervision, Writing – review & editing. AM: Writing – review & be construed as a potential conflict of interest. editing. OC: Writing – review & editing. AF: Writing – review & editing. AA: Writing – review & editing, Funding acquisition, Methodology, Supervision. Publisher’s note All claims expressed in this article are solely those of the authors Funding and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product The author(s) declare that no financial support was received for that may be evaluated in this article, or claim that may be made by its the research, authorship, and/or publication of this article. manufacturer, is not guaranteed or endorsed by the publisher. References 1. Shurson GC. Yeast and yeast derivatives in feed additives and ingredients: sources, condition: a randomized, double-blind, placebo-controlled study. Nutrients. (2020) characteristics, animal responses, and quantification methods. Anim Feed Sci Technol. 12:1–16. doi: 10.3390/nu12123673 (2018) 235:60–76. doi: 10.1016/j.anifeedsci.2017.11.010 16. Sanchez NCB, Broadway PR, Carroll JA. Influence of yeast products on modulating 2. Patterson R, Rogiewicz A, Kiarie EG, Slominski BA. Yeast derivatives as a source of metabolism and immunity in cattle and swine. Animals. (2021) 11:1–14. doi: 10.3390/ bioactive components in animal nutrition: a brief review. Front Vet Sci. (2022) 9:1067383. ani11020371 doi: 10.3389/fvets.2022.1067383 17. Liu Y, Wu Q, Wu X, Algharib SA, Gong F, Hu J, et al. Structure, preparation, 3. Hill C, Guarner F, Reid G, Gibson GR, Merenstein DJ, Pot B, et al. The international modification, and bioactivities of β-glucan and mannan from yeast cell wall: a review. scientific association for probiotics and prebiotics consensus statement on the scope and Int J Biol Macromol. (2021) 173:445–56. doi: 10.1016/j.ijbiomac.2021.01.125 appropriate use of the term probiotic. Nat Rev Gastroenterol Hepatol. (2014) 11:506–14. doi: 10.1038/nrgastro.2014.66 18. Thomas S, Rezoagli E, Abidin IZ, Major I, Murray P, Murphy EJ. Beta-glucans from yeast. Immunomodulators from novel waste resources. Appl Sci. (2022) 12:5208. doi: 4. Fietto JLR, Araújo RS, Valadão FN, Fietto LG, Brandão RL, Neves MJ, et al. 10.3390/app12105208 Molecular and physiological comparisons between Saccharomyces cerevisiae and Saccharomyces boulardii. Can J Microbiol. (2004) 50:615–21. doi: 10.1139/w04-050 19. Heuvelin E, Lebreton C, Grangette C, Pot B, Cerf-Bensussan N, Heyman M. Mechanisms involved in alleviation of intestinal inflammation by Bifidobacterium 5. Bastos TS, Souza CMM, Legendre H, Richard N, Pilla R, Suchodolski JS, et al. Effect Breve soluble factors. PLoS One. (2009) 4:5184. doi: 10.1371/journal.pone. of yeast Saccharomyces cerevisiae as a probiotic on diet digestibility, fermentative 0005184 metabolites, and composition and functional potential of the fecal microbiota of dogs submitted to an abrupt dietary change. Microorganisms. (2023) 11:506. doi: 10.3390/ 20. Okada Y, Tsuzuki Y, Hokari R, Komoto S, Kurihara C, Kawaguchi A, et al. Anti- microorganisms11020506 inflammatory effects of the genus Bifidobacterium on macrophages by modification of phospho-IκB and SOCS gene expression. Int J Exp Pathol. (2009) 90:131–40. doi: 6. Moyad MA, Robinson LE, Kittelsrud JM, Reeves SG, Weaver SE, Guzman AI, et al. 10.1111/j.1365-2613.2008.00632.x Immunogenic yeast-based fermentation product reduces allergic rhinitis-induced nasal congestion: a randomized, double-blind, placebo-controlled trial. Adv Ther. (2009) 21. Riedel CU, Foata F, Philippe D, Adolfsson O, Eikmanns BJ, Blum S. Anti- 26:795–804. doi: 10.1007/s12325-009-0057-y inflammatory effects of bifidobacteria by inhibition of LPS-induced NF- kappaB activation. World J Gastroenterol. (2006) 12:3729–35. doi: 10.3748/wjg.v12. 7. Gibson GR, Hutkins R, Sanders ME, Prescott SL, Reimer RA, Salminen SJ, et al. i23.3729 Expert consensus document: the international scientific association for probiotics and prebiotics (ISAPP) consensus statement on the definition and scope of prebiotics. Nat 22. Nguyen TH, Fleet GH, Rogers PL. Composition of the cell walls of several yeast Rev Gastroenterol Hepatol. (2017) 14:491–502. doi: 10.1038/nrgastro.2017.75 species. Appl Microbiol Biotechnol. (1998) 50:206–12. doi: 10.1007/s002530051278 8. Salminen S, Collado MC, Endo A, Hill C, Lebeer S, Quigley EMM, et al. The 23. Ma T, Tu Y, Zhang NF, Guo JP, Deng KD, Zhou Y, et al. Effects of dietary yeast international scientific association of probiotics and prebiotics (ISAPP) consensus β-glucan on nutrient digestibility and serum profiles in pre-ruminant Holstein calves. J statement on the definition and scope of postbiotics. Nat Rev Gastroenterol Hepatol. Integr Agric. (2015) 14:749–57. doi: 10.1016/S2095-3119(14)60843-1 (2021) 18:649–67. doi: 10.1038/s41575-021-00440-6 24. Kilburn-Kappeler LR, Aldrich CG. Evaluation of a yeast β-glucan blend in a pet 9. Elghandour MMY, Tan ZL, Abu Hafsa SH, Adegbeye MJ, Greiner R, Ugbogu EA, food application to determine its impact on stool quality, apparent nutrient digestibility, et al. Saccharomyces cerevisiae as a probiotic feed additive to non and pseudo-ruminant and intestinal health when fed to dogs. Front Anim Sci. (2023) 4:1125061. doi: 10.3389/ feeding: a review. J Appl Microbiol. (2020) 128:658–74. doi: 10.1111/jam.14416 fanim.2023.1125061 10. Perricone V, Sandrini S, Irshad N, Savoini G, Comi M, Agazzi A. Yeast-derived 25. El-Bab AFF, Saghir SAM, El-Naser IAA, El-Kheir SMMA, Abdel-Kader MF, products: the role of hydrolyzed yeast and yeast culture in poultry nutrition. A review. Alruhaimi RS, et al. The effect of dietary Saccharomyces cerevisiae on growth Animals. (2022) 12:1426. doi: 10.3390/ani12111426 performance, oxidative status, and immune response of sea bream (Sparus aurata). Life. (2022) 12:1013. doi: 10.3390/life12071013 11. Duysburgh C, Van den Abbeele P, Morera M, Marzorati M. Lacticaseibacillus rhamnosus GG and Saccharomyces cerevisiae boulardii supplementation exert protective 26. Matur E, Ergul E, Akyazi I, Eraslan E, Cirakli ZT. The effects of Saccharomyces effects on human gut microbiome following antibiotic administration in vitro. Benefic cerevisiae extract on the weight of some organs, liver, and pancreatic digestive enzyme Microbes. (2021) 12:365–79. doi: 10.3920/BM2020.0180 activity in breeder hens fed diets contaminated with aflatoxins. Poult Sci. (2010) 89:2213–20. doi: 10.3382/ps.2010-00821 12. Moens F, Duysburgh C, van den Abbeele P, Morera M, Marzorati M. Lactobacillus rhamnosus GG and Saccharomyces cerevisiae boulardii exert synergistic antipathogenic 27. Zentek J, Marquart B, Pietrzak T. Intestinal effects of mannanoligosaccharides, activity in vitro against enterotoxigenic Escherichia coli. Benefic Microbes. (2019) transgalactooligosaccharides, lactose and lactulose in dogs. J Nutr. (2002) 132:1682S–4S. 10:923–35. doi: 10.3920/BM2019.0064 doi: 10.1093/jn/132.6.1682S 13. Wang H, Chen G, Li X, Zheng F, Zeng X. Yeast β-glucan, a potential prebiotic, 28. Kaźmierczak-Siedlecka K, Ruszkowski J, Fic M, Folwarski M, Makarewicz W. showed a similar probiotic activity to inulin. Food Funct. (2020) 11:10386–96. doi: Saccharomyces boulardii CNCM I-745: a non-bacterial microorganism used as probiotic 10.1039/D0FO02224A agent in supporting treatment of selected diseases. Curr Microbiol. (2020) 77:1987–96. doi: 10.1007/s00284-020-02053-9 14. Hernández-Macias S, Comas-Basté O, Jofré A, Bover-Cid S, Latorre-Moratalla ML, Vidal-Carou MC. Growth-promoting effect of cava lees on lactic acid Bacteria strains: 29. Czerucka D, Rampal P. Diversity of Saccharomyces boulardii CNCM I-745 a potential revalorization strategy of a winery by-product. Foods. (2021) 10:1636. doi: mechanisms of action against intestinal infections. World J Gastroenterol. (2019) 10.3390/foods10071636 25:2188–203. doi: 10.3748/wjg.v25.i18.2188 15. Tanihiro R, Sakano K, Oba S, Nakamura C, Ohki K, Hirota T, et al. Effects of yeast 30. Tiago FCP, Martins FS, Souza ELS, Pimenta PFP, Araujo HRC, Castro IM, et al. mannan which promotes beneficial bacteroides on the intestinal environment and skin Adhesion to the yeast cell surface as a mechanism for trapping pathogenic bacteria by Frontiers in Veterinary Science 13 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 Saccharomyces probiotics. J Med Microbiol. (2012) 61:1194–207. doi: 10.1099/ 52. Bentley JP, Hunt TK, Weiss JB, Taylor CM, Hanson AN, Davies GH, et al. Peptides jmm.0.042283-0 from live yeast cell derivative stimulate wound healing. Arch Surg. (1990) 125:641–6. doi: 10.1001/archsurg.1990.01410170089019 31. Firon N, Ashkenazi S, Mirelman D, Ofek I, Sharon N. Aromatic alpha-glycosides of mannose are powerful inhibitors of the adherence of type 1 fimbriated Escherichia 53. Crowe MJ, McNeill RB, Schlemm DJ, Greenhalgh DG, Keller SJ. Topical coli to yeast and intestinal epithelial cells. Infect Immun. (1987) 55:472–6. doi: 10.1128/ application of yeast extract accelerates the wound healing of diabetic mice. J Burn Care iai.55.2.472-476.1987 Rehabil. (1999) 20:155–62. doi: 10.1097/00004630-199903000-00032 32. Neeser JR, Koellreutter B, Wuersch P. Oligomannoside-type glycopeptides 54. Goodson W, Hohn D, Hunt TK, Leung DYK. Augmentation of some aspects of inhibiting adhesion of Escherichia coli strains mediated by type 1 pili: preparation of wound healing by a “skin respiratory factor”. J Surg Res. (1976) 21:125–9. doi: potent inhibitors from plant glycoproteins. Infect Immun. (1986) 52:428–36. doi: 10.1016/0022-4804(76)90072-X 10.1128/iai.52.2.428-436.1986 55. Kaplan JZ. Acceleration of wound healing by a live yeast cell derivative. Arch Surg. 33. Spring P, Wenk C, Connolly A, Kiers A. A review of 733 published trials on bio- (1984) 119:1005–8. doi: 10.1001/archsurg.1984.01390210009003 ® ® Mos , a mannan oligosaccharide, and Actigen , a second generation mannose rich fraction, on farm and companion animals. J Appl Anim Nutr. (2015) 3:1–11. doi: 10.1017/ 56. Gruenstein EI, Schlemm DJ, Bethi M, Keller SJ. The early signaling pathway of live yeast cell derivative in THP-1 monocytes. Cell Calcium. (2018) 73:112–20. doi: 10.1016/j. jan.2015.6 ceca.2018.04.008 34. Buts JP, Bernasconi P, Van Craynest MP, Maldague P, Meyer R. Response of human 57. Du B, Bian Z, Xu B. Skin health promotion effects of natural beta-glucan derived from and rat small intestinal mucosa to oral administration of Saccharomyces boulardii. cereals and microorganisms: a review. Phyther Res. (2014) 28:159–66. doi: 10.1002/ptr.4963 Pediatr Res. (1986) 20:192–6. doi: 10.1203/00006450-198602000-00020 58. Oryan A, Jalili M, Kamali A, Nikahval B. The concurrent use of probiotic 35. Buts JP, Bernasconi P, Vaerman JP, Dive C. Stimulation of secretory IgA and microorganism and collagen hydrogel/scaffold enhances burn wound healing: an in vivo secretory component of immunoglobulins in small intestine of rats treated with evaluation. Burns. (2018) 44:1775–86. doi: 10.1016/j.burns.2018.05.016 Saccharomyces boulardii. Dig Dis Sci. (1990) 35:251–6. doi: 10.1007/BF01536771 59. Espinosa C, Esteban MA. Effect of dietary supplementation with yeast 36. Stier H, Bischoff SC. Influence of Saccharomyces boulardii CNCM I-745 on the Saccharomyces cerevisiae on skin, serum and liver of gilthead seabream (Sparus aurata gut-associated immune system. Clin Exp Gastroenterol. (2016) 9:269–79. doi: 10.2147/ L). J Fish Biol. (2020) 97:869–81. doi: 10.1111/jfb.14449 CEG.S111003 60. Sheikhzadeh N, Heidarieh M, Karimi Pashaki A, Nofouzi K, Ahrab Farshbafi M, 37. Castagliuolo I, Thomas Lamont J, Nikulasson ST, Pothoulakis C. Saccharomyces boulardii protease inhibits Clostridium difficile toxin a effects in the rat ileum. Infect ® Akbari M. Hilyses , fermented Saccharomyces cerevisiae, enhances the growth performance and skin non-specific immune parameters in rainbow trout (Oncorhynchus Immun. (1996) 64:5225–32. doi: 10.1128/iai.64.12.5225-5232.1996 mykiss). Fish Shellfish Immunol. (2012) 32:1083–7. doi: 10.1016/j.fsi.2012.03.003 38. Castagliuolo I, Riegler MF, Valenick L, LaMont JT, Pothoulakis C. Saccharomyces 61. Gaspar LR, Camargo FB, Gianeti MD, Maia Campos PMBG. Evaluation of boulardii protease inhibits the effects of Clostridium difficile toxins A and B in human dermatological effects of cosmetic formulations containing Saccharomyces cerevisiae extract colonic mucosa. Infect Immun. (1999) 67:302–7. doi: 10.1128/IAI.67.1.302-307.1999 and vitamins. Food Chem Toxicol. (2008) 46:3493–500. doi: 10.1016/j.fct.2008.08.028 39. Qamar A, Aboudola S, Warny M, Michetti P, Pothoulakis C, LaMont JT, et al. 62. Lu Y, Liu M, Cao Y, Yin J, Zhou H, Yu W, et al. Hydrogel sunscreen based on yeast Saccharomyces boulardii stimulates intestinal immunoglobulin A immune response to /gelatin demonstrates excellent UV-shielding and skin protection performance. Colloids Clostridium difficile toxin A in mice. Infect Immun. (2001) 69:2762–5. doi: 10.1128/ Surf B: Biointerfaces. (2021) 205:111885. doi: 10.1016/j.colsurfb.2021.111885 IAI.69.4.2762-2765.2001 63. Zülli F, Suter F, Biltz H, Nissen HP. Improving skin function with CM-glucan, a 40. Lacotte PA, Simons A, Bouttier S, Malet-Villemagne J, Nicolas V, Janoir C. biological response modifier from yeast. Int J Cosmet Sci. (1998) 20:79–86. doi: 10.1046/j. Inhibition of in vitro Clostridioides difficile biofilm formation by the probiotic yeast 1467-2494.1998.171740.x Saccharomyces boulardii CNCM I-745 through modification of the extracellular matrix 64. Dhurat R, Sharma A, Surve R, McCoy J, Kovacevic M, Goren A, et al. Novel yeast composition. Microorganisms. (2022) 10:1082. doi: 10.3390/microorganisms10061082 extract is superior to colloidal oatmeal in providing rapid itch relief. J Cosmet Dermatol. 41. Izadnia F, Wong CT, Kocoshis SA. Brewer’s yeast and Saccharomyces boulardii both (2021) 20:207–9. doi: 10.1111/jocd.13436 attenuate Clostridium difficile-induced colonic secretion in the rat. Dig Dis Sci. (1998) 65. Zhang Y, Tan Y, Zou Y, Bulat V, Lugovic Mihic L, Kovacevic M, et al. Yeast extract 43:2055–60. doi: 10.1023/A:1018811331596 demonstrates rapid itch relief in chronic pruritus. J Cosmet Dermatol. (2020) 19:2131–4. 42. Martins F, Nardi R, Arantes R, Rosa C, Neves M, Nicoli J. Screening of yeasts as doi: 10.1111/jocd.13265 probiotic based on capacities to colonize the gastrointestinal tract and to protect against 66. Hassan S, Poulos C, Bhatti J, Rangwani S, Khan Z, Mohammed T, et al. enteropathogen challenge in mice. J Gen Appl Microbiol. (2005) 51:83–92. doi: 10.2323/ Saccharomyces cerevisiae as a skin physiology, pathology, and treatment model. Dermatol jgam.51.83 Online J. (2020) 26:1–4. doi: 10.5070/D32611048118 43. Armando M, Dogi C, Pizzolitto R, Escobar F, Peirano M, Salvano M, et al. 67. Doney E, Cadoret A, Dion-Albert L, Lebel M, Menard C. Inflammation-driven Saccharomyces cerevisiae strains from animal environment with in vitro aflatoxin B1 brain and gut barrier dysfunction in stress and mood disorders. Eur J Neurosci. (2022) binding ability and anti-pathogenic bacterial influence. World Mycotoxin J. (2010) 55:2851–94. doi: 10.1111/ejn.15239 4:59–68. doi: 10.3920/WMJ2010.1208 68. Hadizadeh M, Hamidi GA, Salami M. Probiotic supplementation improves the 44. Brandão RL, Castro IM, Bambirra EA, Amaral SC, Fietto LG, Tropia MJM, et al. cognitive function and the anxiety-like behaviors in the stressed rats. Iran J Basic Med Intracellular signal triggered by cholera toxin in Saccharomyces boulardii and Saccharomyces Sci. (2019) 22:506–14. doi: 10.22038/ijbms.2019.33956.8078 cerevisiae. Appl Environ Microbiol. (1998) 64:564–8. doi: 10.1128/AEM.64.2.564-568.1998 69. Babaei F, Mirzababaei M, Mohammadi G, Dargahi L, Nassiri-Asl M. Saccharomyces 45. Roussel C, Sivignon A, de Vallée A, Garrait G, Denis S, Tsilia V, et al. Anti- boulardii attenuates lipopolysaccharide-induced anxiety-like behaviors in rats. Neurosci infectious properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 on Lett. (2022) 778:136600. doi: 10.1016/j.neulet.2022.136600 enterotoxigenic E. coli (ETEC) strain H10407. Appl Microbiol Biotechnol. (2018) 102:6175–89. doi: 10.1007/s00253-018-9053-y 70. Karbownik MS, Kręczyńska J, Wiktorowska-Owczarek A, Kwarta P, Cybula M, Stilinović N, et al. Decrease in salivary serotonin in response to probiotic 46. Sabbatini S, Monari C, Ballet N, Mosci P, Decherf AC, Pélerin F, et al. supplementation with Saccharomyces boulardii in healthy volunteers under psychological Saccharomyces cerevisiae–based probiotic as novel anti-microbial agent for therapy of stress: secondary analysis of a randomized, double-blind, placebo-controlled trial. Front bacterial vaginosis. Virulence. (2018) 9:954–66. doi: 10.1080/21505594.2018.1464362 Endocrinol. (2022) 12:1836. doi: 10.3389/fendo.2021.800023 47. Guo W, Gu X, Tong Y, Wang X, Wu J, Chang C. Protective effects of mannan/β- 71. Tao D, Zhong T, Pang W, Li X. Saccharomyces boulardii improves the behaviour glucans from yeast cell wall on the deoxyniyalenol-induced oxidative stress and autophagy and emotions of spastic cerebral palsy rats through the gut-brain axis pathway. BMC in IPEC-J2 cells. Int J Biol Macromol. (2019) 135:619–29. doi: 10.1016/j.ijbiomac.2019.05.180 Neurosci. (2021) 22:76–16. doi: 10.1186/s12868-021-00679-4 48. Liu G, Yu L, Martínez Y, Ren W, Ni H, Abdullah Al-Dhabi N, et al. Dietary 72. Lee H, Jung Y, Chae J. The effects of Saccharomyces Cerevisiae yeast extract SCP-20 Saccharomyces cerevisiae Cell Wall extract supplementation alleviates oxidative stress on stress response, anxiety and depression: a double-blind placebo-controlled trial. and modulates serum amino acids profiles in weaned piglets. Oxidative Med Cell Longev. Anxiety Mood. (2009) 5:8–13. (2017) 2017:1–7. doi: 10.1155/2017/3967439 73. Bampidis V, Azimonti G, Bastos ML, Christensen H, Dusemund B, Fašmon M, 49. Zhang J, Fang Y, Fu Y, Jalukar S, Ma J, Liu Y, et al. Yeast polysaccharide mitigated et al. Safety and efficacy of a feed additive consisting of Saccharomyces cerevisiae MUCL oxidative injury in broilers induced by mixed mycotoxins via regulating intestinal mucosal oxidative stress and hepatic metabolic enzymes. Poult Sci. (2023) 102:102862. ® 39885 (Biosprint ) for cats and dogs (Prosol S.P.A.). EFSA J. (2021) 19:e06699. doi: 10.2903/j.efsa.2021.6699 doi: 10.1016/j.psj.2023.102862 74. Stercova E, Kumprechtova D, Auclair E, Novakova J. Effects of live yeast dietary 50. Guo H, Guo S, Liu H. Antioxidant activity and inhibition of ultraviolet radiation- supplementation on nutrient digestibility and fecal microflora in beagle dogs. J Anim induced skin damage of selenium-rich peptide fraction from selenium-rich yeast protein Sci. (2016) 94:2909–18. doi: 10.2527/jas.2016-0584 hydrolysate. Bioorg Chem. (2020) 105:104431. doi: 10.1016/j.bioorg.2020.104431 75. Bastos TS, Souza CMM, Kaelle GCB, do Nascimento MQ, de Oliveira SG, Félix 51. Schlemm DJ, Crowe MJ, McNeill RB, Stanley AE, Keller SJ. Medicinal yeast extracts. AP. Diet supplemented with Saccharomyces cerevisiae from different fermentation media Cell Stress Chaperones. (1999) 4:171–6. doi: 10.1379/1466-1268(1999)004<0171:MYE>2.3 modulates the faecal microbiota and the intestinal fermentative products in dogs. J Anim .CO;2 Physiol Anim Nutr. (2023) 107:30–40. doi: 10.1111/jpn.13824 Frontiers in Veterinary Science 14 frontiersin.org Maturana et al. 10.3389/fvets.2023.1279506 76. Oba PM, Carroll MQ, Sieja KM, de Souza Nogueira JP, Yang X, Epp TY, et al. concentrations of protein catabolites in the large bowel of dogs. J Nutr. (2002) 132:980–9. Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, doi: 10.1093/jn/132.5.980 metabolite concentrations, and microbiota populations of dogs subjected to exercise 96. Strickling JA, Harmon DL, Dawson KA, Gross KL. Evaluation of oligosaccharide challenge. J Anim Sci. (2023) 101, 101:1–13. doi: 10.1093/jas/skac424 addition to dog diets: influences on nutrient digestion and microbial populations. Anim 77. Wilson SM, Oba PM, Applegate CC, Koziol SA, Panasevich MR, Norton SA, et al. Feed Sci Technol. (2000) 86:205–19. doi: 10.1016/S0377-8401(00)00175-9 Effects of a Saccharomyces cerevisiae fermentation product-supplemented diet on fecal 97. Rummell LM, Steele MA, Templeman JR, Yohe TT, Akhtar N, Lambie JG, et al. A characteristics, oxidative stress, and blood gene expression of adult dogs undergoing proof of principle study investigating the effects of supplemental concentrated brewer’s transport stress. J Anim Sci. (2023) 101:378. doi: 10.1093/jas/skac378 yeast on markers of gut permeability, inflammation, and fecal metabolites in healthy 78. Wilson SM, Oba PM, Koziol SA, Applegate CC, Soto-Diaz K, Steelman AJ, et al. non-challenged adult sled dogs. J Anim Sci. (2022) 100:1–11. doi: 10.1093/jas/skac281 Effects of a Saccharomyces cerevisiae fermentation product-supplemented diet on 98. Ferreira CS, Vendramini THA, Amaral AR, Rentas MF, Ernandes MC, da Silva FL, circulating immune cells and oxidative stress markers of dogs. J Anim Sci. (2022) et al. Metabolic variables of obese dogs with insulin resistance supplemented with yeast 100:1–11. doi: 10.1093/jas/skac245 beta-glucan. BMC Vet Res. (2022) 18:14–0. doi: 10.1186/s12917-021-03106-2 79. Santos KM, Risolia LW, Rentas MF, Amaral AR, Rodrigues RBA, Urrego MIG, 99. Traughber Z, He F, de Godoy MR, Varney JL, Fowler JW, Coon CN. PSVI-24 et al. Saccharomyces cerevisiae dehydrated culture modulates fecal microbiota and immunological effects of a purified 1,3/1,6 β-glucan supplementation in retorted canine improves innate immunity of adult dogs. Fermentation. (2021) 8:1–19. doi: 10.3390/ diets. J Anim Sci. (2020) 98:313–3. doi: 10.1093/jas/skaa278.558 fermentation8010002 100. Vetvicka V, Oliveira C. β(1-3)(1-6)-D-glucans modulate immune status and 80. Varney JL, Coon CN, Norton SA. PSV-B-20 effects of Saccharomyces Cerevisiae blood glucose levels in dogs. J Pharm Res Int. (2014) 4:981–91. doi: 10.9734/ fermentation product (SCFP) postbiotic in labrador retrievers during exercise and BJPR/2014/7862 transport stress. J Anim Sci. (2021) 99:332–3. doi: 10.1093/jas/skab235.611 101. Rychlik A, Nieradka R, Kander M, Nowicki M, Wdowiak M, Kołodziejska- 81. Lin CY, Alexander C, Steelman AJ, Warzecha CM, De Godoy MRC, Swanson KS. Sawerska A. The effectiveness of natural and synthetic immunomodulators in the Effects of a Saccharomyces cerevisiae fermentation product on fecal characteristics, treatment of inflammatory bowel disease in dogs. Acta Vet Hung. (2013) 61:297–308. nutrient digestibility, fecal fermentative end-products, fecal microbial populations, doi: 10.1556/avet.2013.015 immune function, and diet palatability in adult dogs. J Anim Sci. (2019) 97:1586–99. doi: 10.1093/jas/skz064 102. Beynen AC, Saris DHJ, Paap PM, van Altena F, Visser EA, Middelkoop J, et al. Dietary beta-1,3/1,6-glucans reduce clinical signs of canine atopy. Am J Anim Vet Sci. 82. Strompfová V, Kubašová I, Mudroňová D, Štempelová L, Takáčová M, Gąsowski (2011) 6:146–52. doi: 10.3844/ajavsp.2011.146.152 B, et al. Effect of hydrolyzed yeast administration on faecal microbiota, haematology, serum biochemistry and cellular immunity in healthy dogs. Probiot Antimicrob Prot. 103. Beynen AC, Legerstee E. Influence of dietary beta-1,3/1,6-glucans on clinical (2021) 13:1267–76. doi: 10.1007/s12602-021-09765-9 signs of canine osteoarthritis in a double-blind, placebo-controlled trial. Am J Anim Vet Sci. (2010) 5:97–101. doi: 10.3844/ajavsp.2010.97.101 83. Martins MS, Sakomura NK, Souza DF, Filho FOR, Gomes MOS, Vasconcellos RS, et al. Brewer’s yeast and sugarcane yeast as protein sources for dogs. J Anim Physiol Anim 104. Stuyven E, Verdonck F, Van Hoek I, Daminet S, Duchateau L, Remon JP, et al. Nutr. (2014) 98:948–57. doi: 10.1111/jpn.12145 Oral administration of β-1,3/1,6-glucan to dogs temporally changes total and antigen- specific IgA and IgM. Clin Vaccine Immunol. (2010) 17:281–5. doi: 10.1128/ 84. Kaelle GCB, Souza CMM, Bastos TS, Vasconcellos RS, Oliveira SG, Félix AP. Diet CVI.00344-09 digestibility and palatability and intestinal fermentative products in dogs fed yeast extract. Ital J Anim Sci. (2022) 21:802–10. doi: 10.1080/1828051X.2022.2054733 105. Reilly LM, He F, Rodriguez-Zas SL, Southey BR, Hoke JM, Davenport GM, et al. Use of legumes and yeast as novel dietary protein sources in extruded canine diets. Front 85. Van den Abbeele P, Duysburgh C, Rakebrandt M, Marzorati M. Dried yeast cell Vet Sci. (2021) 8:667642. doi: 10.3389/fvets.2021.667642 walls high in beta-glucan and mannan-oligosaccharides positively affect microbial composition and activity in the canine gastrointestinal tract in vitro. J Anim Sci. (2020) 106. Drill VA. The calorie intake and weight balance of hyperthyroid dogs in relation 98:1–10. doi: 10.1093/jas/skaa173 to vitamin B1 and yeast. Am J Physiol Content. (1941) 132:629–35. doi: 10.1152/ ajplegacy.1941.132.3.629 86. Lin CY, Carroll MQ, Miller MJ, Rabot R, Swanson KS. Supplementation of yeast cell wall fraction tends to improve intestinal health in adult dogs undergoing an abrupt 107. Matheus LFO, Risolia LW, Ernandes MC, de Souza JM, Oba PM, Vendramini diet transition. Front Vet Sci. (2020) 7:905. doi: 10.3389/fvets.2020.597939 THA, et al. Effects of Saccharomyces cerevisiae cell wall addition on feed digestibility, fecal fermentation and microbiota and immunological parameters in adult cats. BMC 87. Theodoro S, Putarov TC, Tiemi C, Volpe LM, de Oliveira CAF, Mb G, et al. Effects Vet Res. (2021) 17:351–10. doi: 10.1186/s12917-021-03049-8 of the solubility of yeast cell wall preparations on their potential prebiotic properties in dogs. PLoS One. (2019) 14:e0225659. doi: 10.1371/journal.pone.0225659 108. Lima LM, Silva JW, Ogoshi RCS, dos Reis JS, Franca J, Zangeronimo MG, et al. Evaluation of raw yeast extract (Saccharomyces cerevisiae) as an ingredient, additive or 88. Beloshapka AN, Dowd SE, Suchodolski JS, Steiner JM, Duclos L, Swanson KS. palatability agent in wet diet for cats. Int J Biol. (2015) 8:1. doi: 10.5539/ijb.v8n1p1 Fecal microbial communities of healthy adult dogs fed raw meat-based diets with or without inulin or yeast cell wall extracts as assessed by 454 pyrosequencing. FEMS 109. Ogoshi RCS, Zangeronimo MG, Dos Reis JS, França J, Santos JPF, Pires CP, et al. Microbiol Ecol. (2013) 84:532–41. doi: 10.1111/1574-6941.12081 Acidifying and yeast extract in diets for adults cats. Anim Sci J. (2014) 85:555–61. doi: 10.1111/asj.12166 89. Beloshapka AN, Duclos LM, Vester BM, Swanson KS. Effects of inulin or yeast cell-wall extract on nutrient digestibility, fecal fermentative end-product concentrations, 110. Aquino AA, Saad FMOB, Santos JPF, Leite CAL, Sampaio GR, Feliciano MAR. and blood metabolite concentrations in adult dogs fed raw meat–based diets. Am J Vet Efeitos da parede de levedura em dieta úmida na microbiota fecal, na produção de gás Res. (2012) 73:1016–23. doi: 10.2460/ajvr.73.7.1016 e na morfologia intestinal de gatos adultos. Arq Bras Med Veterinária Zootec. (2013) 65:1673–80. doi: 10.1590/S0102-09352013000600013 90. Middelbos IS, Godoy MR, Fastinger ND, Fahey GC. A dose-response evaluation of spray-dried yeast cell wall supplementation of diets fed to adult dogs: effects on 111. Aquino AA, Saad FMOB, Santos JPF, Alves MP, Ferrazza RA, Miranda MCMG. nutrient digestibility, immune indices, and fecal microbial populations. J Anim Sci. Efeitos do extrato da parede de levedura na digestibilidade, no escore fecal e na (2007) 85:3022–32. doi: 10.2527/jas.2007-0079 palatabilidade de dietas para gatos. Arq Bras Med Veterinária Zootec. (2010) 62:622–30. doi: 10.1590/S0102-09352010000300018 91. Kroll FSA, Putarov TC, Zaine L, Venturini KS, Aoki CG, Santos JPF, et al. Active fractions of mannoproteins derived from yeast cell wall stimulate innate and acquired 112. Santos J, Aquino A, Glória M, Avila-Campos M, Oba P, Santos K, et al. Effects of immunity of adult and elderly dogs. Anim Feed Sci Technol. (2020) 261:114392. doi: dietary yeast cell wall on faecal bacteria and fermentation products in adult cats. J Anim 10.1016/j.anifeedsci.2020.114392 Physiol Anim Nutr. (2018) 102:1091–101. doi: 10.1111/jpn.12918 92. Pawar MM, Pattanaik AK, Sinha DK, Goswami TK, Sharma K. Effect of dietary 113. Rodrigues BM, Olivo PM, Osmari MP, Vasconcellos RS, Ribeiro LB, Bankuti FI, mannanoligosaccharide supplementation on nutrient digestibility, hindgut fermentation, et al. Microencapsulation of probiotic strains by lyophilization is efficient in maintaining immune response and antioxidant indices in dogs. J Anim Sci Technol. (2017) 59:11. doi: the viability of microorganisms and modulation of fecal microbiota in cats. Int J 10.1186/s40781-017-0136-6 Microbiol. (2020) 2020:1–10. doi: 10.1155/2020/1293481 114. Aktas MS, Borku MK, Ozkanlar Y. Efficacy of Saccharomyces boulardii as a 93. Gouveia EMMF, Silva IS, Nakazato G, Onselem VJV, Corrêa RAC, Araujo FR, et al. probiotic in dogs with lincomycin induced diarrhoea. Bull Vet Inst Pulawy. (2007) Action of phosphorylated mannanoligosaccharides on immune and hematological 51:365–9. responses and fecal consistency of dogs experimentally infected with enteropathogenic Escherichia coli strains. Braz J Microbiol. (2013) 44:499–504. doi: 10.1590/ 115. D’Angelo S, Fracassi F, Bresciani F, Galuppi R, Diana A, Linta N, et al. Effect of S1517-83822013000200027 Saccharomyces boulardii in dogs with chronic enteropathies: double-blinded, placebo- controlled study. Vet Rec. (2018) 182:258–8. doi: 10.1136/vr.104241 94. Grieshop CM, Flickinger EA, Bruce KJ, Patil AR, Czarnecki-Maulden GL, Fahey GC. Gastrointestinal and immunological responses of senior dogs to chicory and 116. Baroncello S, Candiago NT, Gelinski JMLN, Caliari V, Baratto CM. Meat pet mannan-oligosaccharides. Arch Anim Nutr. (2004) 58:483–94. doi: snacks by containing encapsulated Saccharomyces boulardii. Eur J Agric Food Sci. (2020) 10.1080/00039420400019977 2:1–9. doi: 10.24018/ejfood.2020.2.4.69 95. Swanson K, Grieshop C, Flickinger EA, Bauer LL, Healy HP, Dawson KA, et al. 117. De Oliveira RT, Haese D, Kill JL, Lima A, Malini PV, Thompson GR. Supplemental Fructooligosaccharides and mannanoligosaccharides influence immune Palatabilidade de rações de gatos com pirofosfato de sódio e extrato de levedura. Cienc function, ileal and total tract nutrient digestibilities, microbial populations and Rural. (2016) 46:2202–5. doi: 10.1590/0103-8478cr20151651 Frontiers in Veterinary Science 15 frontiersin.org