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Environmental factors, such as antibiotics and diet, have a profound influence on the composition and function of the gut microbiota. While antibiotics consistently disrupt microbial communities, dietary influences are more variable, with some nutrient compositions promoting beneficial microbial activity while others drive dysbiosis. Yet, the subsequent microbiota-mediated effects on mucus function remain incompletely characterised. The colonic mucus layer forms a critical barrier between the gut microbiota and the intestinal epithelium, protecting against infection and inflammation. However, changes in the gut environment can shift microbial metabolism toward degradation of mucin O-glycans, compromising this barrier. To investigate how environmentally-shaped microbiota influence mucus function, human-to-mouse faecal microbiota transplantation (FMT) and ex-vivo mucus function analyses were used throughout this thesis. 

Antibiotics are known to markedly disrupt the gut microbiota, with repeated exposure linked to reduced microbial diversity. However, the consequences for mucus barrier function have remained unclear. To address this, microbiota from individuals with a history of repeated antibiotic exposure were transplanted into microbiota-depleted mice. Recipient mice exhibited significantly reduced mucus growth rate and increased mucus penetrability relative to controls. These functional changes were accompanied by enrichment of known mucin utilisers, including Akkermansia muciniphila and Bacteroides fragilis, together with a distinct metabolite profile. These findings demonstrate that long-term repeated antibiotic exposure can substantially shift microbial composition and function, with direct consequences for mucus barrier integrity. 

Dietary fibre availability shapes bacterial metabolism, with fibre fermentation supporting short-chain fatty acid (SCFA)-mediated mucus barrier function and fibre deficiency promoting mucin degradation. While the effects of the Western-style diets (WSDs) are well described, the consequences of low-carbohydrate diets (LCDs), which are also typically low in fibre, remain unclear. To address this, mice were fed a LCD or transplanted with LCD-shaped human microbiota, resulting in reduced mucus growth rate but unchanged mucus penetrability compared to controls. This indicates that LCD-associated microbiota alter mucus dynamics without fully compromising barrier function, illustrating that not all low-fibre diets exert equally detrimental effects.

Finally, to examine the microbiota-mediated benefits of fibre, FMT experiments were performed using microbiota from individuals who increased their fibre intake for three months. Despite consuming a low-fibre diet, mice receiving the high fibre-shaped human microbiota maintained mucus growth rates comparable to chow-fed controls and exhibited reduced pathogen burden in an intestinal infection model. Both human and mouse microbiota showed increased abundance of Blautia associated with fibre supplementation, and Blautia coccoides was identified as a key species promoting mucus growth through secretion of SCFAs. Functional profiling further revealed an enhanced capacity for dietary fibre degradation relative to mucin-glycans, illustrating how fibre shapes a microbiota capable of preserving mucus barrier integrity. Together, these findings demonstrate a microbiota-mediated protective effect against the otherwise harmful effects of a WSD.

Overall, this thesis advances understanding of how environmental pressures shape microbial communities and thereby influence colonic mucus barrier function. These insights provide a foundation for future mechanistic studies of microbiota–mucus interactions and highlight opportunities to leverage diet and microbial therapeutics to strengthen mucus barrier integrity.