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Gut Microbiota Mediate the Metabolism of Colonic Prostaglandins

ABSTRACT: Prostaglandins (PGs) are lipid signaling molecules that regulate diverse physiological and pathological processes, and their biosynthetic pathways are targets of widely used drugs such as aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs). However, previous research of PG biosynthesis has focused on host metabolic pathways, the roles of gut microbiota involved are not well understood 8. Here, we identify a colonic pathway through which gut microbes directly participate in PG metabolism and regulate colonic PG levels and their biological effects. Comparison of germ-free and conventionally raised mice reveals that the gut microbiota markedly increase the levels of multiple PGs in the colon. This effect is mediated by bacterial β-glucuronidases (GUS), which hydrolyze host-derived PG glucuronides, less active or inactive conjugates, to regenerate bioactive free PGs. GUS administration and bacterial mono-colonization in germ-free mice demonstrate a critical role for microbial GUS in regulating colonic PG levels and associated biological responses. Together, these findings reveal a previously unrecognized function of the gut microbiota in PG metabolism and identify microbial GUS enzymes as potential targets for modulating colonic PG signaling in gastrointestinal diseases.

ORGANISM(S): Mus musculus

PROVIDER: GSE345950 | GEO | 2026/09/04

REPOSITORIES: GEO

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Project description:The mammalian gut harbors a diverse microbial community (gut microbiota) that mainly consists of bacteria. Their combined genomes (the microbiome) provide biochemical and metabolic functions that complement host physiology. Maintaining symbiosis seems to be a key requirement for health as dysbiosis is associated with the development of common diseases. Previous studies indicated that the microbiota and the hostM-bM-^@M-^Ys epithelium signal bidirectional inducing transcriptional responses to fine-tune and maintain symbiosis. However, little is known about the hostM-bM-^@M-^Ys responses to the microbiota along the length of the gut as earlier studies of gut microbial ecology mostly used either colonic or fecal samples. This is of importance as not only function and architecture of the gut varies along its length but also microbial distribution and diversity. Few recent studies have begun to investigate microbiota-induced host responses along the length of the gut. However, these reports used whole tissue samples and therefore do not allow drawing conclusions about specificity of the observed responses. Which cells in the intestinal tissue are responsible for the microbially induced response: epithelial, mesenchymal or immune cells? Where are the responding cells located? We used using extensive microarray analysis of laser capture microdissection (LCM) harvested ileal and colonic tip and crypt fractions from germ-free and conventionally-raised mice to investigate the microbiota-induced transcriptional responses in specific and well-defined cell populations of the hostM-bM-^@M-^Ys epithelium. Ileum and colon segments were dissected from germ-free and conventionally-raised 10-12 weeks old female C57Bl/6 mice, washed and frozen as OCT blocks. Cryosections were prepared from these OCT blocks and tip/crypt fractions isolated using laser capture microdissection. To investigate the microbiota-induced transcriptional responses specific for specific subpopulations of intestinal epithelial cells, tip and crypt fractions of ileal and colonic epithelium of germ-free and conventionally-raised 10-12 weeks old female C57Bl/6 mice were harvested using laser capture microdissection and probed in an extensive microarray analysis.

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Gut Microbiota Mediate the Metabolism of Colonic Prostaglandins

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