Manipulating diet to modulate immunity and disease

Abstract

Diet interacts with immunity in various ways, either directly by impacting the immune cells or indirectly through gut microbiota. Nevertheless, details behind this remain unknown. This thesis investigated the interplays between diet and gut microbiota and the immune system. The underlying mechanisms was also partially characterized like the gut microbiota-derived metabolites and bacterial extracellular vesicles (BEVs) and the microbial metabolite-sensing G-protein-coupled-receptors. Importantly, it also explored the potential of manipulating these factors to modulate immunity and disease.

A comprehensive diet study revealed that dietary carbohydrates, particularly glucose, drove B cell lymphopoiesis and the antibody responses. Mechanistically, glucose fuelled B cell metabolism, activated mTOR signals and protected B cells from apoptosis.

Unexpectedly, the same study found that dietary protein instead, drove the secretory IgA production. A high protein diet boosted the production of BEVs by the gut microbiota, which promoted the T cell-independent IgA production in the epithelium, increasing sIgA.

Additionally, the impact of dietary fibre, a class of complex carbohydrate, on the gut microbiota and the immune system were also studied in West Nile virus disease. Even though shifting the gut microbiota, a high fibre diet imposed little effect on the disease and was not effective in alleviating the virus-induced inflammation.

Finally, the role of GPR109A, a receptor of the dietary fibre-derived metabolites from the gut microbiota, in Treg development was studied. In addition to its involvement in intestinal Treg generation, the impact of GPR109A on thymic Treg induction was reported and its role in a multiple sclerosis animal model, experimental autoimmune encephalomyelitis, was elucidated.

Collectively, this thesis provides novel insights into the complex crosstalk among diet, gut microbiota and immunity. It sheds light on manipulating diet to treat diseases.