Received: 2 May 2019 | Revised: 30 July 2019 | Accepted: 1 August 2019 DOI: 10.1111/nmo.13703 ORIGINAL ARTICLE Abdominal distension after eating lettuce: The role of intestinal gas evaluated in vitro and by abdominal CT imaging Elizabeth Barba1,2 | Borja Sánchez3,4 | Emanuel Burri5 | Anna Accarino1,2 | 6 6 1,2 3,4 Eva Monclus | Isabel Navazo | Francisco Guarner | Abelardo Margolles | 1,2 Fernando Azpiroz 1 Digestive System Research Unit, University Hospital Vall d'Hebron, Centro de Abstract Investigación Biomédica en Red de Background: Some patients complain that eating lettuce, gives them gas and abdomi‐ Enfermedades Hepáticas y Digestivas (Ciberehd), Barcelona, Spain nal distention. Our aim was to determine to what extent the patients' assertion is 2 Departament de Medicina, Universitat sustained by evidence. Autònoma de Barcelona, Bellaterra, Spain Methods: An in vitro study measured the amount of gas produced during the process 3 Departamento de Microbiología y Bioquímica, Instituto de Productos Lácteos of fermentation by a preparation of human colonic microbiota (n = 3) of predigested de Asturias (IPLA), Consejo Superior de lettuce, as compared to beans, a high gas‐releasing substrate, to meat, a low gas‐ Investigaciones Científicas, Asturias (CSIC), Villaviciosa, Spain releasing substrate, and to a nutrient‐free negative control. A clinical study in pa‐ 4 Instituto de Investigación Sanitaria del tients complaining of abdominal distention after eating lettuce (n = 12) measured the Principado de Asturias–ISPA, Oviedo, Spain amount of intestinal gas and the morphometric configuration of the abdominal cavity 5 Kantonsspital Baselland, Liestal, in abdominal CT scans during an episode of lettuce‐induced distension as compared Switzerland 6 Departamento de Lenguajes y Sistemas to basal conditions. Informáticos, Universidad Politécnica de Key Results: Gas production by microbiota fermentation of lettuce in vitro was Catalunya, Barcelona, Spain similar to that of meat (P = .44), lower than that of beans (by 78 ± 15%; P < .001) Correspondence and higher than with the nutrient‐free control (by 25 ± 19%; P = .05). Patients com‐ Fernando Azpiroz, Digestive System Research Unit, Hospital General Vall plaining of abdominal distension after eating lettuce exhibited an increase in girth d'Hebron, 08035‐Barcelona, Spain. (35 ± 3 mm larger than basal; P < .001) without significant increase in colonic gas Email: azpiroz.fernando@gmail.com content (39 ± 4 mL increase; P = .071); abdominal distension was related to a descent Funding information of the diaphragm (by 7 ± 3 mm; P = .027) with redistribution of normal abdominal This work was supported in part by the Spanish Ministry of Economy and contents. Competitiveness (Dirección General de Conclusion and Inferences: Lettuce is a low gas‐releasing substrate for microbiota Investigación Científica y Técnica, SAF 2016‐76648‐R); Ciberehd is funded by the fermentation and lettuce‐induced abdominal distension is produced by an uncoordi‐ Instituto de Salud Carlos III. nated activity of the abdominal walls. Correction of the somatic response might be more effective than the current dietary restriction strategy. KEYWORDS abdominal distension, diaphragmatic activity, functional gut disorders, intestinal gas, lettuce Elizabeth Barba and Borja Sanchez contributed equally as first authors. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2019 The Authors. Neurogastroenterology & Motility published by John Wiley & Sons Ltd Neurogastroenterology & Motility. 2019;31:e13703.  wileyonlinelibrary.com/journal/nmo | 1 of 7 https://doi.org/10.1111/nmo.13703 2 of 7 | BARBA et al. 1 | I NTRO D U C TI O N Key Points Some patients complain that eating lettuce gives them gas and ab‐ • Some patients complain that eating lettuce gives them dominal distention. Our aim was to determine to what extent the gas and abdominal distention; however, there is no evi‐ patients' assertion is sustained by evidence. dence in support of this assertion. The food ingested undergoes a process of digestion in the oral • Lettuce is a low gas‐releasing substrate for microbiota cavity, stomach, and small intestine before the resulting chime en‐ fermentation both in vitro and in vivo; lettuce‐induced ters the colon. Food residues within the colon serve as substrates abdominal distension is a somatic expression with dia‐ for microbiota metabolism. Fermentation of food residues by micro‐ phragmatic contraction and protrusion of the anterior biota releases gas at an amount that depends on the type of sub‐ abdominal wall. strate; gas production is large with fermentable carbohydrates, and • Identification of the conditioning mechanism of this re‐ low with proteins and fat.1 sponse would help to develop a more specific treatment The abdominal wall actively adapts to its content by a tight reg‐ than the current dietary restriction strategy. ulation of its muscular activity. 2,3 Considering these two elements, ie wall and content, abdominal distension in patients may be related to either an increase in abdominal content, eg intestinal gas accumu‐ lation, or to a dyssynergia of the abdominal walls and redistribution were boiled for 30 minutes in 1 L of water leaving them to soak in of normal content; the latter is a conditioned response that can be the same water at room temperature for another 30 minutes; fresh corrected by behavioral treatment.4-6 lettuce was used without any cooking treatment. To address our aim, a two‐phase study was performed. An in vitro study measured the amount of gas produced during the pro‐ 2.1.2 | In vitro digestion cess of microbiota fermentation of lettuce, as compared to a high gas‐releasing substrate, a low gas‐releasing substrate and a nutri‐ In order to mimic the digestive process, a standardized static in vitro 10 ent‐free negative control. Beans were used as a high gas‐releasing digestion method was used following international guidelines ; 7 substrate by human colonic microbiota demonstrated both in vivo the composition of Simulated Salivary Fluid (SSF), Simulated Gastric and in vitro,8,9 and cow meat, with a very low content of non‐diges‐ Fluid (SGF), and Simulated Intestinal Fluid (SIF) has been reported tive fermentable polysaccharides, as a potential low gas‐releasing in detail.10 substrate. After a pre‐processing mimicking cooking and oro‐gastro‐ intestinal digestion, each foodstuff was incubated with a prepara‐ Oral digestion tion of human colonic microbiota, and the amount of gas released by Samples (5 g) of each foodstuff and the nutrient‐fee control were fermentation was measured. In a clinical phase, patients complaining homogenized with 5 mL of prewarmed SSF at 37ºC in a compact of abdominal distention after eating lettuce were studied, measuring masticator paddle blender (Reference code 100085/058; IUL the amount of intestinal gas and the morphometric configuration of Instruments, Barcelona, Spain) during 1 minute, and incubated for the abdominal cavity in abdominal CT scans during an episode of 2 minutes at 37ºC; SSF contained 1.5 mmol/L CaCl2 and 75 U/mL lettuce‐induced distension as compared to basal conditions. human salivary α‐amylase Type IX‐A (ref. A0521; Sigma‐Aldrich). Gastric digestion 2 | M ATE R I A L A N D M E TH O DS The resulting oral bolus was mixed with 10 mL of prewarmed SGF, the mix was adjusted to pH 3 with HCl and incubated for 2 hours at 37ºC 2.1 | In vitro study: Gas production during with mild shaking every 30 minutes; SGF contained 0.15 mmol/L fermentation of specific foodstuffs by human colonic CaCl2 and 2000 U/mL porcine pepsin (ref. P7000; Sigma‐Aldrich). microbiota Gas production was measured in batch fecal microbiota prepara‐ Intestinal digestion tions from healthy donors cultivated in the presence of in vitro di‐ After the gastric phase, 20 mL of prewarmed SIF was added to the gested foods. gastric chime, the pH was adjusted to 7.0 with NaOH and the re‐ sulting mixture was incubated for 2 hours at 37ºC with mild shaking every 30 minutes; SIF contained 0.6 mmol/L CaCl2 and 100 U/mL 2.1.1 | Test foodstuffs and preparation porcine pancreatin (ref. P7545; Sigma‐Aldrich) and 10 mmol/L por‐ Four preparations were tested: iceberg lettuce (Lactuca sativa), cow cine bile salts (ref. B8631; Sigma‐Aldrich). meat (Bos taurus; sirloin) and broad beans (Phaseolus vulgaris, variety After the simulated digestion, the samples of the four prepara‐ “Granja Asturiana”), and a nutrient‐free negative control (phosphate‐ tions (the three digested foodstuffs and the nutrient‐free negative buffered saline, PBS). To reproduce cooking conditions, 50 g cow control) were divided in three different aliquots and immediately meat was boiled for 20 minutes in 1 L of water, and 50 g broad beans stored at −80ºC. BARBA et al. | 3 of 7 calculation was performed; data on abdominal CT imaging have not 2.1.3 | Colonic microbiota preparations been previously published. Fecal samples were obtained from three newly recruited donors without known diseases, gastrointestinal symptoms, antibiotic 2.2.2 | Experimental procedure intake in the past 6 months and with normal bowel habit. Fecal slurries of each sample were prepared, as follows: An aliquot (4 g) After having recognized lettuce as the reproducible offending meal, of each fecal sample was thoroughly mixed in a total volume of ie patients knew that eating lettuce would give them abdominal dis‐ 40 mL PBS during 5 minutes using a Lab Blender 400 Stomacher tension, two visits were scheduled within a 2‐day interval: patients (ref. 432‐0161; Seward Medical) and A modified 2× basal medium were instructed to report in the laboratory (a) during fasting when was prepared by adding 4 g/L peptone water, 4 g/L yeast extract, they felt minimal or no abdominal distension (basal conditions), 0.2 g/L NaCl, 0.08 g/L K 2HPO 4, 0.08 g/L KH2PO 4, 0.02 g/L MgSO 4, (b) and within 1 hour after eating the offending foodstuff (lettuce 0.02 g/L CaCl2.2H2O, 4 g/L NaHCO3, 5 g/L L‐cysteine‐HCl, 4 mL/L salad dressed at taste). During each condition (basal and distension) Tween‐80, and 0.1 g/L haemin.11 With each individual's microbiota, the subjective sensation of abdominal distension and abdominal four slots were prepared by mixing 40 mL of the 2× basal medium girth were measured, and a CT scan was taken, as detailed below. with 8 mL fecal slurries and 20 mL of sterile dH2O. Afterward, patients were offered a biofeedback treatment to cor‐ rect abdominal distension. 2.1.4 | Preparation of fecal cultures 2.2.3 | Subjective sensation of abdominal distension Each slot of microbiota preparation was mixed with 12 mL of one of the previously digested preparations: lettuce, ie the test meal, meat, The patient's subjective sensation of abdominal distension was ie the low gas‐producing control, beans, ie the high gas‐ producing measured on a 6‐score graphic rating scale graded from 0 (no disten‐ control, and the nutrient‐free negative control. Gas production by sion) to 6 (extremely severe distension). each of the three independent fecal microbiotas fed with the dif‐ ferent substrates (total 12 preparations) was monitored using the 2.2.4 | Girth measurement ANKOMRF Gas Production System (ANKOM Technology) in an an‐ aerobic workstation (MG500 Anaerobic Workstation, Don Whitley The method has been previously described and validated in de‐ Scientific) at 37ºC during 30 hours, under a H2:CO2:N2 (1:1:8) atmos‐ tail.13-17 Briefly, a non‐stretch belt (48‐mm wide) with a metric tape phere. Gas production in each preparation was continuously moni‐ measure fixed over it was placed over the umbilicus. The overlap‐ tored by measuring the increment in pressure. ping ends of the belt were adjusted carefully by two elastic bands to maintain the belt constantly adapted to the abdominal wall. Girth measurements were taken with the subjects breathing quietly as 2.2 | Clinical study the average of inspiratory and expiratory determinations over three consecutive respiratory cycles without manipulation of the belt‐tape 2.2.1 | Participants assembly by the investigator. In the first measurement (basal condi‐ Twelve women (age range 24‐58 years) who complained of ab‐ tions or distension episode), the location of the belt was marked on dominal distension after eating lettuce participated in the study. the skin for subsequent measurements. Only patients who reported episodes of visible distension related to ingestion of lettuce in contrast to basal periods with mild or no 2.2.5 | Abdominal CT imaging and analysis distension were included in the study. The entry criteria required lettuce as the primary offending foodstuff, regardless that other Abdominal CT scans were performed blindly with the operator una‐ green leafy vegetables could have a deleterious effect as well. All ware of the condition (basal or distension) of the patient. The CT patients had a functional disorder diagnosis based on Rome III scan during lettuce‐induced distension was taken 1 hour after in‐ 12 criteria : 8 functional bloating (7.1 ± 0.5 bowel movements per gestion. Scanning was performed with a helical multislice CT scan‐ week; 3.2 ± 0.3 score on the Bristol stool form scale) and four con‐ ner (Somatom Definition AS, Siemens Medical Solutions), exposure stipation‐predominant irritable bowel syndrome (2.2 ± 0.3 bowel 120 kV and 50 mAs, using the available dose reduction options (tube movements per week, 2.0 ± 0.4 Bristol score). Symptom duration current modulation); 2‐mm section thickness and 1.5‐mm interval was 6 ± 4 years. reconstruction. Images were obtained in the supine position during The study protocol had been previously approved by the a single breath‐hold at the end of expiration. No oral or intravenous Institutional Review Board of the University Hospital Vall d’He‐ contrast medium was administered. bron, and all subjects gave their written informed consent to partic‐ Analysis of CT images was performed blindly. Morphovolumetric ipate in the study. This study is an exploratory arm of a larger study analysis of CT images was performed using an original software (ClinicalTrials.gov NCT01205100) involving a subset of patients who program specifically developed in our laboratory and previously de‐ fulfilled the inclusion criteria described above, and hence, no power scribed in detail.6,18 4 of 7 | BARBA et al. After each biofeedback session, patients were instructed to per‐ form the same exercises daily at home for 5 minutes before and after breakfast, lunch, and dinner. By the end of treatment, the subjective sensation of abdominal distension and abdominal girth were measured. 2.3 | Statistical analysis Results of the “in vitro” study are presented as the mean (±SE) of the three biological replicates for each of the three foodstuffs and the control solution. Mean values or grand means for re‐ peated observations on the clinical study, ie treatment sessions of the parameters measured (±SE) were calculated in each group of subjects. Normality was tested by the Kolmogorov‐Smirnov test. F I G U R E 1 Gas production by microbiota fermentation in vitro. Comparisons of parametric, normally‐distributed data were made The three predigested foodstuff and the nutrient‐free control were by the paired Student's t test; otherwise, the Wilcoxon signed‐ incubated with preparations of human colonic microbiota (n = 3). Gas production by microbiota fermentation of lettuce was similar rank test was used. to that of meat (a low gas‐releasing substrate), 78 ± 15% lower than that of beans (a high gas‐releasing substrate; P < .001) and 25 ± 19% higher than with the nutrient‐free control (P = .05) 3 | R E S U LT S 3.1 | In vitro gas production Gas volume in the gut To measure the volume of gas within the gut, images were filtered Gas production by microbiota fermentation of lettuce, the test with a user‐defined threshold to separate gas from tissues. product, was similar than that of meat, the low gas‐producing con‐ trol. Gas production by both preparations was significantly lower Abdominal morphometric analysis than that during fermentation of beans, the high gas‐producing Abdominal perimeter was measured by averaging the perimeter of control, and higher than with the negative nutrient‐free control the abdominal surface measured in 10 axial slices 4 mm apart at the (Figure 1). level of the umbilicus; at each site, the perimeter was measured as the length of a polyline (series of connected segments) following the 3.2 | Clinical study body contour. Antero‐posterior abdominal diameter was measured as the distance (in the antero‐posterior axis) between the anterior 3.2.1 | Abdominal bloating and distension aspect of the vertebral bodies and the midline surface of the anterior abdominal wall; the average of the values measured at six levels (L1 When patients complained of distension after ingestion of lettuce, to S1) was calculated in each subject. Position of the diaphragm was the subjective sensation of abdominal distension (4.5 ± 0.2 score) measured as the distance (in the vertical axis) between the left dia‐ was significantly higher than during basal condition (2.0 ± 0.4 phragmatic dome and the cranial end‐plate of the twelfth thoracic score; P < .001). Furthermore, objective measurement of abdomi‐ vertebra (T12). nal girth by tape measure also detected significant differences Total abdominal volume (gas plus liquids and solids) was mea‐ compared to basal conditions (35 ± 3 mm larger than in the basal sured as the body volume between a cranial plane (tangential to the session; P < .001). diaphragmatic domes and perpendicular to the vertebral spine) and a caudal plane (defined by bony structures in the pelvis) subtracting 3.2.2 | Content of gas within the digestive tract the volume corresponding to the lungs and the heart. In the CT scans taken during basal conditions, the volume of gas in the colon was 85 ± 16 mL. Gas was evenly distributed along the 2.2.6 | Biofeedback treatment colon within the different compartments (Figure 2). During ab‐ Patients received EMG‐guided training during the three treatment dominal distension, the gas volume in the colon tended to increase sessions on separate days within a 2‐week period, as described (by 39 ± 4 mL), but the difference was not statistically significant before. 5,19 In brief, patients were trained to control the activity of (P = .071; Figure 2). The volume of gas in the small bowel (24 ± 14 mL the abdomino‐thoracic muscles under visual control of EMG re‐ in the basal scan) and in the stomach (12 ± 2 mL basal) also tended cordings displayed on a monitor. Specifically, they were instructed to increase (increase by 12 ± 9 mL and by 41 ± 10 mL, respectively) to reduce the activity of intercostal muscles and the diaphragm, but the differences were not statistically significant (P = .089 and while increasing the activity of the anterior abdominal muscles. P = .111, respectively). BARBA et al. | 5 of 7 F I G U R E 2 Distribution of gas in the colon. During a lettuce‐ induced episode of abdominal distension, colonic gas content F I G U R E 3 Abdominal CT image in a patient during basal tended to be higher, but not significantly, than during basal conditions and during an episode of lettuce‐induced distension. conditions. To note, the absolute differences were small and would Note that abdominal distension is associated to a diaphragmatic hardly account for the abdominal distension descent (blue arrow) and anterior wall protrusion (orange arrow) without substantial increase of intestinal gas 3.2.3 | Mechanism of abdominal distension Abdominal morphometric analysis our study does not elucidate the specific factors in lettuce and the Morphometric analysis of abdominal CT images showed that ab‐ underlying mechanisms leading to the abnormal somatic response. dominal distension was associated with a marked increase in ab‐ After eating lettuce, gas content in the colon increased but to an dominal girth (20 ± 2 mm greater than in basal scans; P < .001), extent that would hardly account for an episode of visible abdominal confirming the tape measurements, and in the antero‐posterior distension. The increase in gas content observed was probably re‐ abdominal diameter (16 ± 5 mm greater than in the basal scan; lated to the arrival into the colon of complex carbohydrates resistant P = .011). Abdominal distension was associated with a caudal dis‐ to small bowel digestion. The amount of colonic gas and the intralu‐ placement of the diaphragm, measured as a decrease in the dis‐ minal distribution of the gaseous mass, both during basal conditions tance from the diaphragmatic dome to T12 (7 ± 3 mm descent; as well as after eating lettuce, was within the normal range observed P = .027; Figure 3). The difference in total intraabdominal volume in healthy subjects during fasting and after a regular meal.18,20-22 (between the fasting basal scan and the postprandial distension The clinical data are supported by the in vitro study. Fermentation scan was 835 ± 187 mL. of lettuce by colonic microbiota in vitro produced a similar amount of gas as meat, with a low content of carbohydrates, and significantly Reponses to biofeedback treatment less than beans, high in fermentable carbohydrates. During physi‐ Under the visual guidance provided by the EMG signal, all patients ological conditions in humans, fermentation of meal residues by were able to effectively control their abdominal muscular activity. colonic microbiota can be monitored by measuring colonic gas pro‐ Treatment was associated with a significant improvement in the sub‐ duction. 23-26 Gas production peaks after ingestion with the arrival jective sensation of abdominal distension (from 4.5 ± 0.2 score to into the colon of fresh substrates escaping small bowel absorption; 2.2 ± 0.3 score; 50 ± 7% reduction; P < .001) and decrease in girth subsequently gas production declines, 24 but still the fecal material (by 50 ± 2 mm; P < .001). evacuated contains fermentable residues. Indeed, the presence of fermentable residues in the fecal samples may explain the produc‐ tion of gas in vitro with the nutrient‐free negative control. The static 4 | D I S CU S S I O N in vitro digestion method, recommended by international consen‐ sus,10 does not reproduce the absorption of nutrients that normally Our data indicate that when patients complain of abdominal disten‐ occurs in the small bowel, and hence, gas production after eating let‐ tion produced by gas after eating lettuce, abdominal distention is tuce in vivo would be even smaller, because digestible carbohydrates real, but their interpretation is incorrect. Indeed, abdominal disten‐ would not arrive into the colon. sion is not produced by intestinal gas, but by an uncoordinated activ‐ Previous studies in healthy subjects using abdominal CT imag‐ ity of the abdominal walls, with contraction of the diaphragm, caudal ing combined with EMG of the abdominal walls showed that the displacement of abdominal content and protrusion of the anterior anterior wall and the diaphragm, adapt their muscular tone to the abdominal wall. The response to behavioral treatment suggests that intraabdominal content. Increases of intraabdominal content, induce this is a conditioned response. Hence, our exploratory study shows an abdominal accommodation response, featuring a relaxation and that: (a) lettuce may produce objective abdominal distension, (b) dis‐ upward displacement of the diaphragm with cephalad expansion of tension is not related to gas, and (c) it is related to a somatic behav‐ the abdominal cavity and limited impact on the anterior abdominal ioral response. Beyond these main pieces of reasonable evidence, wall.3,17,27,28 The present study shows that abdominal distension 6 of 7 | BARBA et al. after eating lettuce in our patients is produced by a paradoxical con‐ supervision of studies, data analysis. EM. Adaptation of CT analysis traction of the diaphragm with caudo‐ventral redistribution of ab‐ program. IN. Adaptation of CT analysis program. FG. Data interpre‐ dominal content. This mechanism of abdominal distension has been tation, manuscript revision. AM. Study design, in vitro studies, data also detected in other patients with episodic abdominal distension analysis, manuscript revision. FA. Study design, data interpretation, not specifically related to meals.5,6 To treat this condition, we devel‐ manuscript preparation. oped in our laboratory a biofeedback technique that allows patients to control the activity of the abdominal walls.5,19 The fact that our ORCID patients learned to modulate the activity of the abdominal walls, and thereby prevented lettuce‐induced distension, suggests that the lat‐ Elizabeth Barba http://orcid.org/0000-0002-5986-6592 ter is a behavioral response under volitional control. Anna Accarino https://orcid.org/0000-0002-5829-1811 We wish to acknowledge that this pilot study included a small Fernando Azpiroz https://orcid.org/0000-0002-7327-960X sample size and did not include proper controls for the specificity of lettuce as the offending foodstuff. Furthermore, we can only spec‐ ulate on the mechanisms of conditioning, ie what in lettuce and by REFERENCES which mechanism triggers the abnormal somatic response. An in‐ 1. Azpiroz F. Intestinal gas. In Feldman M, Friedman LS, Brand LJ, eds. teresting study by the Nottingham group has recently shown that Pathophysiology, Diagnosis, Management (10th ed). Philadelphia, PA: lettuce increases water content in the small bowel, possibly due to Elsevier; 2015; 242‐250. irritant latex‐like lactucins inducing secretion. 29 In our study, the in‐ 2. Villoria A, Azpiroz F, Burri E, Cisternas D, Soldevilla A, Malagelada crement in total intraabdominal contents in the postprandial disten‐ JR. Abdomino‐phrenic dyssynergia in patients with abdominal sion scan was within the normal range and would normally elicit a bloating and distension. Am J Gastroenterol. 2011;106:815‐819. 3. Burri E, Cisternas D, Villoria A, et al. Accommodation of the ab‐ proper abdominal accommodation. However, in sensitive individuals domen to its content: integrated abdomino‐thoracic response. either the irritant component in lettuce or even a relatively small Neurogastroenterol Motil. 2012;24(4):312‐e162. increase small bowel water content not detectable by CT imaging, 4. Barba E, Quiroga S, Accarino A, et al. Mechanisms of abdominal may release the abnormal response. Alternatively, or additionally, distension in severe intestinal dysmotility: abdomino‐thoracic re‐ sponse to gut retention. Neurogastroenterol Motil. 2013;25(6):e389 lettuce‐induced distension may be related to cognitive/affective ‐e394. factors: anticipation may trigger the behavioral response, ie condi‐ 5. Barba E, Burri E, Accarino A, et al. Abdomino‐thoracic mechanisms tioned patients might become distended if they believe they will. In of functional abdominal distension and correction by biofeedback. general, stress is reported as a frequent triggering factor, which sup‐ Gastroenterology. 2015;148(4):732‐738. 6. Accarino A, Perez F, Azpiroz F, Quiroga S, Malagelada JR. Abdominal ports the potential role of the mental sphere.30 Nevertheless, why distension results from caudo‐ventral redistribution of contents. these patients in the first place learned this abnormal behavior is Gastroenterology. 2009;136:1544‐1551. not known. 7. Steggerda FR. Gastrointestinal gas following food consumption. The straightforward management of this condition relays on di‐ Ann NY Acad Sci. 1968;150:57‐66. 8. McBurney MI, Thompson LU. Effect of human faecal inoculum on in etary restriction avoiding the offending foodstuff, but this is cum‐ vitro fermentation variables. Br J Nutr. 1987;58(2):233‐243. bersome and in the long run may result unpractical. Disentangling 9. Granito M, Champ M, David A, Bonnet C, Guerra M. Identification the conditioned behavior may be a better strategy. Currently, decon‐ of gas‐producing components in different varieties of Phaseolus vul- ditioning of these patients may be achieved focussing on the somatic garis by in vitro fermentation. J Sci Food Agric. 2001;81(6):543‐550. 10. Minekus M, Alminger M, Alvito P, et al. A standardised static in vitro mechanism of distension by biofeedback; however, the identification digestion method suitable for food ‐ an international consensus. of the specific origin of conditioning and the triggering factor would Food Funct. 2014;5(6):1113‐1124. allow a more selective and effective alternative. 11. Arboleya S, Salazar N, Solis G, et al. In vitro evaluation of the impact of human background microbiota on the response to Bifidobacterium strains and fructo‐oligosaccharides. Br J Nutr. AC K N OW L E D G M E N T S 2013;110(11):2030‐2036. 12. Longstreth GF, Thompson WG, Chey WD, Houghton LA, Mearin The authors thank Gloria Santaliestra for secretarial assistance. F, Spiller RC. Functional bowel disorders. Gastroenterology. 2006;130(5):1480‐1491. 13. Tremolaterra F, Villoria A, Azpiroz F, Serra J, Aguade S, Malagelada C O N FL I C T O F I N T E R E S T JR. Impaired viscerosomatic reflexes and abdominal wall dystony associated with bloating. Gastroenterology. 2006;130:1062‐1068. No competing interests declared. 14. Passos MC, Tremolaterra F, Serra J, Azpiroz F, Malagelada JR. Impaired reflex control of intestinal gas transit in patients with ab‐ dominal bloating. Gut. 2005;54:344‐348. AU T H O R C O N T R I B U T I O N S 15. Salvioli B, Serra J, Azpiroz F, et al. Origin of gas retention and symp‐ toms in patients with bloating. Gastroenterology. 2005;128:574‐579. EBarba. Clinical study management, conduction of experiments. BS. 16. Caldarella MP, Serra J, Azpiroz F, Malagelada JR. Prokinetic ef‐ Study design, in vitro studies, data analysis, manuscript preparation. fects in patients with intestinal gas retention. Gastroenterology. EBurri. Design of the original clinical study. AA. Clinical study design, 2002;122:1748‐1755. BARBA et al. | 7 of 7 17. Burri E, Barba E, Huaman JW, et al. Mechanisms of postprandial a proof‐of‐concept‐study. Aliment Pharmacol Ther. abdominal bloating and distension in functional dyspepsia. Gut. 2017;45(6):670‐680. 2014;63:395‐400. 26. Mego M, Accarino A, Tzortzis G, et al. Colonic gas homeostasis: 18. Perez F, Accarino A, Azpiroz F, Quiroga S, Malagelada J‐R. Gas dis‐ mechanisms of adaptation following HOST‐G904 galactooligosac‐ tribution within the human gut: effect of meals. Am J Gastroenterol. charide use in humans. Neurogastroenterol Motil. 2017;29(9):e13080. 2007;102:842‐849. 27. Villoria A, Azpiroz F, Soldevilla A, Perez F, Malagelada JR. Abdominal 19. Barba E, Accarino A, Azpiroz F. Correction of abdominal distention accommodation: a coordinated adaptation of the abdominal walls by biofeedback‐guided control of abdominothoracic muscular ac‐ to its content. Am J Gastroenterol. 2008;103:2807‐2815. tivity in a randomized, placebo‐controlled trial. Clin Gastroenterol 28. Burri E, Cisternas D, Villoria A, et al. Abdominal accommodation Hepatol. 2017;15(12):1922‐1929. induced by meal ingestion: differential responses to gastric and co‐ 20. Bendezú RA, Barba E, Burri E, et al. Intestinal gas content and dis‐ lonic volume loads. Neurogastroenterol Mot. 2013;25:339‐e253. tribution in health and in patients with functional gut symptoms. 29. Wilkinson‐Smith VC, Major G, Ashleigh L, et al. Insights into the dif‐ Neurogastroenterol Motil. 2015;27(9):1249‐1257. ferent effects of food on intestinal secretion using magnetic reso‐ 21. Bendezú RA, Barba E, Burri E, et al. Colonic content in health and nance imaging. JPEN J Parenter Enteral Nutr. 2018;42(8):1342‐1348. its relation to functional gut symptoms. Neurogastroenterol Motil. 30. Azpiroz F, Malagelada JR. Abdominal bloating. Gastroenterology. 2016;28:849‐854. 2005;129:1060‐1078. 22. Bendezú RA, Mego M, Monclus E, et al. Colonic content: ef‐ fect of diet, meals, and defecation. Neurogastroenterol Motil. 2017;29(2):e12930. How to cite this article: Barba E, Sánchez B, Burri E, et al. 23. Mego M, Bendezu A, Accarino A, Malagelada JR, Azpiroz F. Intestinal gas homeostasis: disposal pathways. Neurogastroenterol Abdominal distension after eating lettuce: The role of Motil. 2015;27:363‐369. intestinal gas evaluated in vitro and by abdominal CT 24. Mego M, Accarino A, Malagelada JR, Guarner F, Azpiroz F. imaging. Neurogastroenterol Motil. 2019;31:e13703. https​:// Accumulative effect of food residues on intestinal gas production. doi.org/10.1111/nmo.13703​ Neurogastroenterol Motil. 2015;27(11):1621‐1628. 25. Mego M, Manichanh C, Accarino A, et al. Metabolic ad‐ aptation of colonic microbiota to galactooligosaccharides: