Stool Microbiota, Metabolites, and Fecal Incontinence in Women

IMPORTANCE: Stool metabolites influencing gut motility and sensation may contribute to fecal incontinence (FI). OBJECTIVE: The objective of this study was to test whether FI is associated with higher levels of butyrate and Clostridiales taxa in stool. STUDY DESIGN: Stool metabolites and microbiota were compared between 96 women with FI and 42 controls. FI frequency and subtype (urgency vs insensible) were measured using a 14-day bowel diary, St. Mark's score, and the Accidental Bowel Leakage questionnaire. Metabolite analysis included targeted analysis (8 short-chain fatty acids including butyrate, 17 bile acids, and 8 tryptophan derivatives) and untargeted analysis. Stool microbiota were characterized using 16S rRNA gene sequencing. Multivariable and exploratory multiomics factor analysis were performed with statistical significance defined as false discovery rate (FDR) ≤0.10. RESULTS: The FI group had a higher proportion of Bristol stool types 2 and 6 than controls (P = 0.005). The mean number of leaks for the FI group was 1.7 ± 1.7 per day, 38% had urgency FI, and 39% had insensible FI. There was no significant difference between groups in butyrate levels and Clostridiales taxa. Multiomics analysis identified glycerolipids (monoacylglycerols and diacylglycerols) associated with FI (FDR = 0.08). In addition, insensible FI was associated with glycerolipids, long-chain saturated and monounsaturated fatty acids, phospholipids, and dipeptides (FDR = 0.08-0.09). The top weighted microbiota associated with these metabolites were Lachnospiraceae and Ruminococcaceae; however, these taxa were not directly associated with FI. CONCLUSION: Butyrate and Clostridiales were not associated with FI. Novel stool metabolite signatures were identified, suggesting new biological pathways and potential therapeutic targets for FI.