Disease progression-associated alterations in fecal metabolites in SAMP1/YitFc mice, a Crohn's disease model.

Abstract

Crohn's disease (CD) is a chronic, relapsing inflammatory bowel disease affecting the gastrointestinal tract. Although its precise etiology has not been fully elucidated, an imbalance of the intestinal microbiota has been known to play a role in CD. Fecal metabolites derived from microbiota may be related to the onset and progression of CD OBJECTIVES: This study aimed to clarify the transition of gut microbiota and fecal metabolites associated with disease progression using SAMP1/YitFc mice, a model of spontaneous CD METHODS: The ileum tissues isolated from SAMP1/YitFc mice at different ages were stained with hematoxylin-eosin for histologic characterization with CD progression. Feces from control, Institute of Cancer Research (ICR; n = 6), and SAMP1/YitFc (n = 8) mice at different ages were subjected to microbial analysis and 1H nuclear magnetic resonance (NMR) analysis to investigate fluctuations in gut microbiota and fecal metabolites with CD progression RESULTS: Relative abundance of the Lachnospiraceae, Ruminococcaceae, Bacteroidaceae, and Bacteroidales S24-7 at family-level gut microbiota and fecal metabolites, such as short-chain fatty acids, lactate, glucose, xylose, and choline, dramatically fluctuated with histologic progression of intestinal inflammation in SAMP1/YitFc mice. Unlike the other metabolites, fecal taurine concentration in SAMP1/YitFc mice was higher than ICR mice regardless of age CONCLUSION: The fecal metabolites showing characteristic fluctuations may help to understand the inflammatory mechanism associated with CD, and might be utilized as potential biomarkers in predicting CD pathology.