Regulation of enteroendocrine networks and mediation of gut-brain communication by Bacteroides thetaiotaomicron

Modasia, Amisha (2022) Regulation of enteroendocrine networks and mediation of gut-brain communication by Bacteroides thetaiotaomicron. Doctoral thesis, University of East Anglia.

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Recent research has shed light onto the bi-directional relationship between the gastrointestinal microbiome and the brain, termed the gut-microbiota-brain axis, implicated in many metabolic, psychiatric, and neurological disorders. Bacteroides thetaiotaomicron (Bt) is one of the most abundant symbiont species of the human gastrointestinal tract (GIT) and has important roles in maintaining host homeostasis. Like other fermentative members of the gut microbiota, Bt produces an array of short-chain and organic acids, that in addition to serving as energy sources, are important signalling molecules in host communication pathways including the neuroendocrine system, through recognition by G-protein coupled receptors (GPCRs) present on host cells in the GIT. Furthermore, Bt along with other gram-negative and gram-positive bacteria, produces a diverse array of membrane vesicles, termed bacterial extracellular vesicles (BEVs) that are increasingly being recognised as long-distance mediators in communication between the gut microbiota and host tissues.

To gain further insight into the role of Bt and its mediators in communication between the host gut and brain, a multifaceted approach utilising in vivo animal models and in vitro cell culture-based systems was carried out. The results presented in this Thesis demonstrate the ability of Bt to singularly regulate intestinal enteroendocrine cell (EEC) networks in vivo through the production of its major fermentation products, acetate, propionate, and succinate (APS), with these findings also recently published (Modasia A et al., 2020). In addition to microbial fermentation products, nano-sized BEVs have begun to recieve growing interest in contributing to host physiology, including immune, neurological and metabollic functions. Using BEVs isolated from Bt cultures (Bt-BEVs) and in vitro cell culture systems modelling the gut-brain axis, demonstrate the ability of Bt-BEVs to cross gut epithelial and brain endothelial cell barriers. Following translocation across these cellular barriers, Bt-BEVs were shown to be acquired by central nervous system (CNS) microglia and neurones and then sequestered to the intracellular lysosomal pathway. These experiments highlight the potential of Bt to indirectly modulate host gut-brain pathways through production of metabolites and BEVs.

Item Type: Thesis (Doctoral)
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Chris White
Date Deposited: 16 Nov 2022 13:19
Last Modified: 16 Nov 2022 13:19


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