부산대학교 도서관

Our gut harbours a biosphere of microorganisms constantly responding to the environmental cues we provide for them. From what we eat to how we behave and when we get sick so can our gut microbiome. However, this is not a one-way communication, these microorganisms also work for us in regulating many aspects of our body's biochemical, physiological and immune functions. The gut microbiome lives in different compartments of varying nutrient availabilities, chemical and physiological conditions. The highly fluctuant environment of the small intestine (SI) and the presence bile acids and oxygen render this compartment inhabitable by most species. However, Streptococcus spp. thrive in the SI because they are highly efficient at metabolising simple carbohydrates for energy. Chapter 3 showed certain strains Streptococcus spp. may be in competition with one another for the availability of nutrients in the SI. Inside the colon, these facultative anaerobes were replaced by a diverse community of obligate anaerobes capable for fermenting complex carbohydrates, proteins and even mucin glycans. These microbial communities are resilient and adaptable to short-term Western diet intervention although carbohydrate fermentation activity of the colonic microbiota was decreased as Chapter 3 showed. In Chapter 4, significant alterations in the community structure and metabolic capacity of the colonic microbiota were observed in patients with irritable bowel syndrome (IBS). Lower carbohydrate fermentation and increased protein fermentation were evident in patients with constipation-predominant IBS. Diarrhoea-predominant IBS patients excreted more primary bile acids. Using multi-omics integration, a novel host-microbial co-metabolic pathway involving purine salvage was identified. Chapter 5 showed the passage of short chain fatty acids (SCFA) from the lumen to the mucosa was interrupted by the presence of a mucus layer. A diffusion dynamic for the trans- compartmental passage of SCFA was subsequently hypothesised. This thesis presents a compartmentalised view of the gut microbiome, demonstrating its unique adaptations to dietary change and that disturbances in its community structure and functional capacity underlie the pathophysiology of functional gastrointestinal disorders.