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GNPS - The genetic background is shaping cecal enlargement in the absence of intestinal microbiota

ABSTRACT: Germ-free (GF) animal models represent a unique tool to study the function and impact of gut microbiota on the host under homeostatic or pathologic conditions. GF animals can be selectively colonized with specific microorganisms of interest or even microbial communities. Therefore, these models are frequently employed to decipher complex interactions between the host and its endogenous commensal microbiota, as well as to study interrelations between microbial species within the specific biotope such as intestine.

INSTRUMENT(S): TripleTOF 6600

ORGANISM(S): Mus Musculus (ncbitaxon:10090)

SUBMITTER: Marijana Basic

PROVIDER: MSV000090765 | GNPS | Tue Nov 22 02:54:00 GMT 2022

REPOSITORIES: GNPS

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Project description:Chronic diseases arise when pathophysiological processes achieve a steady state by self-reinforcing. Here, we explored the possibility of a self-reinforcement state in a common condition, chronic constipation, where alterations of the gut microbiota have been reported. The functional impact of the microbiota shifts on host physiology remains unclear, however we hypothesized that microbial communities adapted to slow gastrointestinal transit affect host functions in a way that reinforces altered transit, thereby maintaining the advantage for microbial self-selection. To test this, we examined the impact of pharmacologically (loperamide)-induced constipation (PIC) on the structural and functional profile of altered gut microbiota. PIC promoted changes in the gut microbiome, characterized by decreased representation of butyrate-producing Clostridiales, decreased cecal butyrate concentration and altered metabolic profiles of gut microbiota. PIC-associated gut microbiota also impacted colonic gene expression, suggesting this might be a basis for decreased gastrointestinal (GI) motor function. Introduction of PIC-associated cecal microbiota into germ-free (GF) mice significantly decreased GI transit time. Our findings therefore support the concept that chronic diseases like constipation are caused by disease-associated steady states, in this case, caused by reciprocating reinforcement of pathophysiological factors in host-microbe interactions. We used microarrays to detail the global gene expression profile in the proximal colon smooth muscle tissues of germ-free, conventionalized, or specific pathogen free mouse C57Bl/6 female and male specific pathogen free (SPF) mice were bred and housed in the animal care facility at the University of Chicago. Mice of 8–10 weeks of age were treated with 0.1% loperamide in the drinking water for 7 days. Age matched, germ-free (GF) C57Bl/6 mice were gavaged orally with cecal luminal contents harvested from control or loperamide-treated C57Bl/6 donor mice. Recipient mice were sacrificed 4 weeks post-colonization.

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GNPS - The genetic background is shaping cecal enlargement in the absence of intestinal microbiota

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