Topical Area: Nutritional Microbiology, Nutrient-Gene Interactions
Objectives : It is clear that epidemiologic trends document a dramatic increasing incidence of inflammatory bowel disease (IBD) paralleling global westernization. Despite strong tie among diets, gut microbiota (GM) and IBD, the exact mechanisms causing IBD remains incompletely understood. Here we hypothesized that changes in the gut immune system, in response to changes in gut microbiome induced "Westernized diet", would be sufficient to trigger IBD.
We set out to test this hypothesized by analyzing the changes in gut microbiota composition induced by feeding mice with High sugar-solution or/and High fat and demonstrated their causal roles through high-throughput microbiome analyses. We further assessed changes in inflammatory cell recruitment using flow cytometry, and performed transcriptomic profiling analyses of intestine tissue to identify altered gut microbiota deliver changes in intestinal innate immune and adaptive T cell homeostasis. Importantly, to identify the role of the microbiota in directing host immune responses, fecal microbiota transplantation (FMT) experiments were conducted.
Results : The microbiome analyses results showed that Prevotella, Betaproteobacteria, and Cytophaga, which are a well-known the most representative species in IBD, was significantly enriched only in the HF-Sugar group, suggesting that addition of high-sugar to high-fat diet may reshape the GM by favoring colonization of pathobionts. Also, transcriptome and FACS profiling results showed, among others, high sugar synergistically changes intestinal transcriptomic signature related Inflammatory/Immune Response induced by several pro-inflammatory cytokines and induces expansion of inflammatory DCs and T cells driven by the high fat diet. By using FMT, we prove that host immune traits can be regulated by altering the GM.
Together, our large-scale profiling analyses may uncover an interaction between dietary alterations causing IBD and gut microbiota and provide helpful information regarding the microbiota plays a critical role in programming the immune phenotypes of the host.
Funding Sources : This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2018R1D1A1B07048023).