Abstract
Introduction
Studies of gastrointestinal physiology and the gut microbiome often consider the influence of intestinal region on experimental endpoints. However, this same consideration is not often applied to the gut metabolome. Understanding the contribution of gut regionality may be critically important to the rapidly changing metabolic environments, such as during pregnancy.
Objectives
We sought to characterize the difference in the gut metabolome in pregnant mice stratified by region—comparing the small intestine, cecum, and feces. Pre-pregnancy feces were collected to understand the influence of pregnancy on the fecal metabolome.
Methods
Feces were collected from CD-1 female mice before breeding. On gestation day (GD) 18, gut contents were collected from the small intestine, cecum, and descending colon. Metabolites were analyzed with LC–MS/MS using the Biocrates MetaboINDICATOR™ MxP® Quant 500 kit.
Results
Of the 104 small molecule metabolites meeting analysis criteria, we found that 84 (81%) were differentially abundant based on gut region. The most significant regional comparison observed was between the cecum and small intestines, with 52 (50%) differentially abundant metabolites. Pregnancy itself altered 41 (39.4%) fecal small molecule metabolites.
Conclusions
The regional variation observed in the gut metabolome are likely due to the microbial and physiological differences between the different parts of the intestines. Additionally, pregnancy impacts the fecal metabolome, which may be due to evolving needs of both the dam and fetus.
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Data availability
Data used for analysis can be found at https://data.gov.
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The authors thank Drs. Justin Conley, Ian Gilmour, Christopher Lau, and Katie O’Shaughnessy for their careful review of this manuscript.
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This study was funded by the Sustainable and Healthy Communities Research Program in the Office of Research and Development at the U.S. Environmental Protection Agency. This research was also supported in part by an appointment to the Research Participation Program at the Center for Public Health and Environmental Assessment at the U.S. EPA administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. EPA.
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MM, JD, MS, and CM conceived and contributed to the design of the experiment. MM prepared the samples and JF conducted the metabolomics. TJ and MM analyzed data. MM wrote the manuscript. All authors participated in the review and revision of the manuscript and approved the final version.
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Moore, M.L., Ford, J.L., Schladweiler, M.C. et al. Gut metabolic changes during pregnancy reveal the importance of gastrointestinal region in sample collection. Metabolomics 20, 40 (2024). https://doi.org/10.1007/s11306-024-02099-x
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DOI: https://doi.org/10.1007/s11306-024-02099-x