2e2bf149fd58488f322caf6c2f4cb044 nutrients-17-03003-v2.pdf 94fafb0e73b30a13b573919269e297937df50e4c nutrients-17-03003-v2.pdf ba0bc2521874e497932ccc4e8fb277a36ad5d6138ae25a483ef9cd68a3b8dba9 nutrients-17-03003-v2.pdf Title: Fecal Short-Chain Fatty Acids to Predict Prediabetes and Type 2 Diabetes Risk: An Exploratory Cross-Sectional Study Subject: Background/Objectives: Gut microbiota is profoundly influenced by dysglycemic states, including prediabetes (preDM) and type 2 diabetes (T2D). Although short-chain fatty acids (SCFAs) may serve as proxies reflecting these microbial changes, their predictive role remains elusive. This study aimed to evaluate the association between fecal SCFA concentrations and glycemic status (preDM and T2D), using individuals with normoglycemia (NonDM) as the reference group in a Mediterranean adult population. Methods: This study included a total of 88 participants from the Di@bet.es study who were classified into three groups according to the American Diabetes Association criteria: NonDM (45%), preDM (27%), and T2D (28%), respectively. We evaluated gut microbiota populations through massive sequencing and determined SCFAs concentration using gas chromatography–mass spectrometry. Adjusted multiple logistic regression models were used to estimate associations between SCFAs and metabolic status. Results: The mean age of subjects with preDM and T2D was approximately 68 years, older than that of NonDM participants (about 60 years). About 50% of the subjects in the NonDM and preDM groups were female, whereas in the T2D group, females represented about 25%. The analysis revealed that only fecal acetic acid was significantly reduced in T2D compared to NonDM (p = 0.036) and preDM (p = 0.018) groups. Remarkably, fecal acetic acid was negatively associated with T2D risk when taking preDM as the reference state (OR = 0.561 [95% CI: 0.371–0.846],p = 0.009). Intriguingly, fecal acetic acid was identified as a significant positive predictor of preDM risk, taking the NonDM group as reference (OR = 1.422; p = 0.028), while propionic acid was inversely associated with preDM (OR = 0.714; p = 0.028). Conclusions: Our analysis showed that fecal acetic acid levels were associated with a reduced risk of T2D but also with an increased risk of preDM; however, the biological relevance of these findings remains uncertain. Keywords: dysglycemia; dietary intake; clinical studies; microbial metabolites; gut microbiota; SCFA profiles; metabolic risk factors Author: Rocío Puig, Marina Idalia Rojo-López, Josep Julve, Esmeralda Castelblanco, Julia Ponomarenko, Susana Amézqueta, Joan Vendrell, Josep Franch-Nadal, Josep Lluís Torres, Dídac Mauricio and Sara Ramos-Romero Creator: LaTeX with hyperref Producer: pdfTeX-1.40.25; modified using OpenPDF 1.4.2 CreationDate: Tue Sep 23 10:57:43 2025 CEST ModDate: Tue Sep 23 11:19:49 2025 CEST Custom Metadata: yes Metadata Stream: no Tagged: no UserProperties: no Suspects: no Form: none JavaScript: no Pages: 17 Encrypted: no Page size: 595.276 x 841.89 pts (A4) Page rot: 0 File size: 1713604 bytes Optimized: no PDF version: 1.5 name type encoding emb sub uni object ID ------------------------------------ ----------------- ---------------- --- --- --- --------- AIRHKL+VnURWPalladioL Type 1 Custom yes yes yes 144 0 BPVQTZ+URWPalladioL-Bold Type 1 Custom yes yes yes 145 0 JLROFV+URWPalladioL-Roma Type 1 Custom yes yes yes 146 0 MNFVLA+URWPalladioL-Ital Type 1 Custom yes yes yes 147 0 UWJUYN+CMSY10 Type 1 Builtin yes yes yes 209 0 XSVVIN+EURM10 Type 1 Builtin yes yes yes 229 0 WBVKDJ+URWPalladioL-BoldItal Type 1 Custom yes yes yes 242 0 EOEDOJ+PalatinoLinotype TrueType WinAnsi yes yes no 261 0 EOEDOH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 262 0 EOEDPL+PalatinoLinotype,Italic TrueType WinAnsi yes yes no 285 0 EOEDOJ+PalatinoLinotype TrueType WinAnsi yes yes no 286 0 EOEDOJ+PalatinoLinotype TrueType WinAnsi yes yes no 302 0 EOEDOH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 303 0 EOEDOJ+PalatinoLinotype TrueType WinAnsi yes yes no 310 0 EOEDOH+PalatinoLinotype,Bold TrueType WinAnsi yes yes no 311 0 Jhove (Rel. 1.28.0, 2023-05-18) Date: 2025-09-24 03:08:47 CEST RepresentationInformation: nutrients-17-03003-v2.pdf ReportingModule: PDF-hul, Rel. 1.12.4 (2023-03-16) LastModified: 2025-09-23 18:08:33 CEST Size: 1713604 Format: PDF Version: 1.5 Status: Well-Formed and valid SignatureMatches: PDF-hul MIMEtype: application/pdf PDFMetadata: Objects: 522 FreeObjects: 1 IncrementalUpdates: 0 DocumentCatalog: ViewerPreferences: HideToolbar: false HideMenubar: false HideWindowUI: false FitWindow: true CenterWindow: false DisplayDocTitle: false NonFullScreenPageMode: UseNone Direction: L2R ViewArea: CropBox ViewClip: CropBox PrintArea: CropBox PageClip: CropBox PageLayout: SinglePage PageMode: UseNone Outlines: Item: Title: Introduction Item: Title: Materials and Methods Children: Item: Title: Study Design and Subjects Item: Title: Study Procedures Item: Title: Classification of Glycemic Status Item: Title: Food Frequency Questionnaire Item: Title: Urinary Sugar Excretion Analysis Item: Title: Fecal DNA Extraction and Sequencing for Microbiota Populations Analysis Item: Title: Fecal Short-Chain Fatty Acids Item: Title: Statistical Analyses Item: Title: Results Children: Item: Title: Demographic and Clinical Characteristics Item: Title: Dietary Intake Patterns Item: Title: Composition of Gut Microbiota in Feces Item: Title: Fecal Short-Chain Fatty Acids (SCFAs) Item: Title: Correlation Between SCFAs and Gut Microbial Genera Item: Title: Microbial and Metabolic Predictors of Dysglycemia Children: Item: Title: PreDM vs. NonDM Item: Title: T2D vs. NonDM Item: Title: T2D vs. PreDM Item: Title: Discussion Item: Title: Conclusions Item: Title: References Info: Title: Fecal Short-Chain Fatty Acids to Predict Prediabetes and Type 2 Diabetes Risk: An Exploratory Cross-Sectional Study Author: Rocío Puig, Marina Idalia Rojo-López, Josep Julve, Esmeralda Castelblanco, Julia Ponomarenko, Susana Amézqueta, Joan Vendrell, Josep Franch-Nadal, Josep Lluís Torres, Dídac Mauricio and Sara Ramos-Romero Subject: Background/Objectives: Gut microbiota is profoundly influenced by dysglycemic states, including prediabetes (preDM) and type 2 diabetes (T2D). Although short-chain fatty acids (SCFAs) may serve as proxies reflecting these microbial changes, their predictive role remains elusive. This study aimed to evaluate the association between fecal SCFA concentrations and glycemic status (preDM and T2D), using individuals with normoglycemia (NonDM) as the reference group in a Mediterranean adult population. Methods: This study included a total of 88 participants from the Di@bet.es study who were classified into three groups according to the American Diabetes Association criteria: NonDM (45%), preDM (27%), and T2D (28%), respectively. We evaluated gut microbiota populations through massive sequencing and determined SCFAs concentration using gas chromatography–mass spectrometry. Adjusted multiple logistic regression models were used to estimate associations between SCFAs and metabolic status. Results: The mean age of subjects with preDM and T2D was approximately 68 years, older than that of NonDM participants (about 60 years). About 50% of the subjects in the NonDM and preDM groups were female, whereas in the T2D group, females represented about 25%. The analysis revealed that only fecal acetic acid was significantly reduced in T2D compared to NonDM (p = 0.036) and preDM (p = 0.018) groups. Remarkably, fecal acetic acid was negatively associated with T2D risk when taking preDM as the reference state (OR = 0.561 [95% CI: 0.371–0.846],p = 0.009). Intriguingly, fecal acetic acid was identified as a significant positive predictor of preDM risk, taking the NonDM group as reference (OR = 1.422; p = 0.028), while propionic acid was inversely associated with preDM (OR = 0.714; p = 0.028). Conclusions: Our analysis showed that fecal acetic acid levels were associated with a reduced risk of T2D but also with an increased risk of preDM; however, the biological relevance of these findings remains uncertain. 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