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Colonic gene expression in mice mono-colonized with E.coli HA107

ABSTRACT: The gut microbiota can influence brain function and behaviour through several mechanisms. The first critical step that initiates microbial-host interaction which leads to the establishment of normal behavior is unknown. In this study, we identified that activation of the innate immune system by microbes is a critical step in the initiation of the gut-brain communication. We showed that bacterial mono-colonization was sufficient to initiate the normalization of behavior which critically depends on Toll-like receptors. To investigate the mechanisms by which immune system activation affects behavior, we assessed the colonic immune gene expression profile from germ-free Swiss Webster and MyD88-/- Ticam-/- mice before and after mono-colonization with E.coli HA107 bacterial strain. To identify the relevant pathways, we searched for genes that fulfilled the criteria based on the behavioral tests: (1) change in transcripts at 2 weeks and (2) similar expression between 2 and 4 weeks post-colonization in C57BL/6 mice; 3) unchanged expression in MyD88-/- Ticam-/- mice. These criteria were fulfilled by 26 genes, mainly related to the innate immunity. Ingenuity pathway analysis revealed that many were related both to immune function and neural development and behavior. These results raise the possibility that impaired postnatal microbiota-host cross talk could affect normal brain maturation process and lead to altered neurodevelopment and psychiatric disorders later in life.

ORGANISM(S): Mus musculus

PROVIDER: GSE138319 | GEO | 2025/12/01

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? Furthermore, the gut microbiota has been implicated in epigenetic regulation of the hostM-bM-^@M-^Ys transcriptional profile. We used using extensive microarray analysis of laser capture microdissection (LCM) harvested ileal and colonic tip and crypt fractions from germ-free mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) to investigate the microbiota-induced transcriptional responses and their kinetics in specific and well-defined cell populations of the hostM-bM-^@M-^Ys epithelium. Ileum and colon segments were dissected from germ-free 10-12 weeks old female C57Bl/6 mice and on day 1, 3, 5 and 7 after colonization, 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 and their kinetics, tip and crypt fractions of ileal and colonic epithelium of germ-free 10-12 weeks old female C57Bl/6 mice before and during the time course of colonization with a normal microbiota (on days 1, 3, 5 and 7) were harvested using laser capture microdissection and probed in an extensive microarray analysis.

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Colonic gene expression in mice mono-colonized with E.coli HA107

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