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

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Abstract

Introduction

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.

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Acknowledgements

We are grateful to Dr. Hiroyuki Kumeta, Dr. Yasuhiro Kumaki, and Dr. Yuki Ohnishi of the Open Facility Division, Global Facility Center, Creative Research Institution, Hokkaido University for performing the NMR analysis using NMR spectrometer and for providing insight and expertise that greatly assisted the research. This research was supported by grants from the Center of Innovation Program from Japan Science and Technology Agency, JST, Grant Number JPMJCE1301.

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Authors and Affiliations

  1. Graduate School of Life Science, Hokkaido University, Sapporo, 060-0810, Japan

    Yosuke Komatsu, Yu Shimizu, Megumi Yamano, Kiminori Nakamura, Tokiyoshi Ayabe & Tomoyasu Aizawa

  2. Wellness & Nutrition Science Institute, Morinaga Milk Industry Co., Ltd., Zama, Japan

    Yosuke Komatsu

  3. Division of Cell Biological Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan

    Mani Kikuchi, Kiminori Nakamura & Tokiyoshi Ayabe

  4. Department of Advanced Transdisciplinary Science, Faculty of Advanced Life Science, Hokkaido University, Sapporo, Japan

    Tomoyasu Aizawa

  5. Global Station for Soft Matter, Global Institution for Collaborative Research and Education, Hokkaido University, Sapporo, Japan

    Tomoyasu Aizawa

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  1. Yosuke Komatsu
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Contributions

MY performed the animal experiments and the microbiome study. YS performed the NMR measurement. YK analyzed all data and wrote the paper. YK, MK, KN, TA, and TA contributed to the study conception and design. TA holds the primary responsibility for the final content. All authors have read and approved the final manuscript.

Corresponding author

Correspondence to Tomoyasu Aizawa.

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Conflict of interest

Y.K. is an employee of Morinaga Milk Industry Co., Ltd. The other authors declare no conflict of interest.

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Komatsu, Y., Shimizu, Y., Yamano, M. et al. Disease progression-associated alterations in fecal metabolites in SAMP1/YitFc mice, a Crohn’s disease model. Metabolomics 16, 48 (2020). https://doi.org/10.1007/s11306-020-01671-5

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