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Unlocking the mysterious interconnection between the gut microbiota and catestatin

PhD ceremony:D.P. Gonzalez Davila
When:June 28, 2022
Start:16:15
Supervisor:S. (Sahar) El Aidy, PhD
Co-supervisor:dr. S.K. Mahata
Where:Academy building RUG
Faculty:Science and Engineering

The mammalian gut harbors a diverse microbial community with a vast metabolic capacity, collectively referred to as the gut microbiome. A unique interplay occurs between a subtype of cells of the gut epithelium, namely, enteroendocrine cells and the microbiota. Enteroendocrine cells secrete an extensive number of hormones and bioactive peptides, which play a key role in modulating mucosal immunity, gut motility, and metabolism. Among these bioactive peptides is catestatin (CST), which is derived from the prohormone chromogranin-A. CST has been shown to regulate innate mucosal immunity, gut permeability, hypertension, as well as a potential diabetes treatment.

In this thesis, we showed that CST selects for the colonization of gut bacterial communities that are capable of resisting its antimicrobial effect, which in turn, impacts the levels of butyrate and other short-chain fatty acids and subsequently gut motility. Furthermore, we showed via fecal microbial transplantation, that the altered gut microbiota in mouse models with depletion in their CST play a causal role in the colonic dysfunction observed in those mice, characterized by increased gut permeability, fibrosis, and altered immune- and metabolic-related cellular pathways. Overall, this thesis exemplifies the pivotal interplay between the gut microbiota and CST, in the establishment and maintenance of mucosal homeostasis and opens new avenues for microbiota-targeted therapeutics in humans for specific diseases associated with altered levels of CST.

See also: 

New insights into how the gut regulates bacterial communities

and

Fecal transplant throws new light on inflammatory bowel disease