Investigation of host-microbiota communication through diverse signalling pathways

Abstract

The gut microbiota plays a fundamental role in shaping host physiology, influencing

immune homeostasis, metabolism, and overall health. Disruptions in gut homeostasis, driven by altered dietary patterns and antibiotic exposure, are strongly linked to the rising incidence of non-communicable diseases (NCDs) through microbiota-mediated mechanisms. However, identifying precise signalling pathways and their contributions to disease remains challenging, partly due to the vast diversity of microbiota-derived molecules that can influence host processes. While microbial metabolites and microbe-associated molecular patterns (MAMPs) are well-established mediators of the gut-host axis, emerging evidence suggests that gut microbiota extracellular vesicles (MEVs) represent an additional pathway that integrates metabolite and MAMP signalling.

Although specific MEV strains and total MEV profiles are increasingly studied as potential therapeutics and biomarkers, their physiological role in gut-host interactions remains poorly understood. This thesis explores how gut microbiota and MEVs influence key aspects of host physiology, focusing on their roles in immunity, metabolism, and maternal-fetal interactions.

Collectively, this thesis explores the relationship between microbiota and host physiology, examining how antibiotics and diet influence this interplay and identifying

MEVs as key mediators in this cross-talk. While further studies are needed to elucidate the precise molecular mechanisms by which MEVs regulate host biology, these findings highlight their potential as both a therapeutic target and a novel intervention to modulate microbiota-driven pathways in NCD development.