Gut microbiome resilience: is the emergence of intestinal pathobionts determined by poor diet?

Abstract

Gut microbiome resilience is the recovery capacity of the microbiome following a perturbation (e.g. antibiotics or unhealthy diet). Diets high in fruit and vegetables, rich in fibre, low in simple sugars and saturated fat are inversely correlated with chronic disease risk compared to the westernised diet, high in saturated fat and refined foods. Impairment of the gut microbiome allows infection by opportunistic pathogens (pathobionts) such as Clostridioides difficile, a major cause of healthcare-associated infection. Previous study highlighted that the colonic milieu reflects the metabolic outputs of specific dietary patterns. This allowed to investigate, in vitro, the impact of a certain diet on the microbiome and C. difficile.

 A literature review investigated the relationship between diet and microbiome, analysing also the implication of colonisation resistance, resilience and the impact on pathobionts infections such as C. difficile. The impact of dietary fibres and the relative metabolites on C. difficile 630 was analysed in first place in vitro, via a faecal microbiota batch fermenter model. Here it was demonstrated that simple and complex fermentable fibres affect the metabolome and the induce changes which can improve colonisation resistance. For example, a complex fermentable fibre demonstrated to significantly increase the concentration of butyrate (p < 0.05). A human intervention study involving a plant-based and a western diet was performed to determine the effects of such diet on microbiome composition and host health, demonstrating, for example, that plant-based diet significantly reduced the concentration of total and primary bile acids (p < 0.05) this can increase protection towards conditions such as type 2 diabetes. From the best responder of this study generated faecal water, was co-cultured with C. difficile 630 to determine the iii effects of both the plant-based and the western diet on gene expression. The plant-based diet compared to the western increased the expression of spore coat protein such as cotCB (FC = 2.74), cotA (FC = 2.78), cotD (FC = 2.57) and cotF (2.39) (p-value < 0.001). This showed that plant-based diet, compared to western, can induce sporulation, which is a marker of cellular stress for C. difficile.

 In conclusion, this thesis demonstrated that dietary fibres could improve protection towards pathobionts by interacting with the microbiome.

Thesis is embargoed until 30th June 2026

Date of Award	Jun 2024
Original language	English
Sponsors	Fondazione Edmund Mach (FEM)
Supervisor	Nigel Ternan (Supervisor) & Chris Gill (Supervisor)