Association Between Urbanization-Related Change In Diet, The Gut Microbiota And Microbiome-Related Metabolites In A Rapidly Urbanizing Environment In China

Introduction: Numerous studies suggest that there are rural-urban differences in gut microbial community, partially due the Westernization of diet. However, most studies are based on short-term follow-up and cannot assess how the transition from traditional to Western diets over time shapes human gut microbiota and whether these microbiota changes subsequently impact the metabolomic profile of the host. Hypothesis: We hypothesize that trajectories in diet shape components of the gut microbial community, with strong associations for microbiota and microbiome-mediated metabolites. Methods: We used growth mixture models to estimate individual-specific intercepts (current % calories from animal source food in 2015) and slopes (change in % calories from animal source food from 1991-2015) in 1,468 adults from the population-based China Health and Nutrition Survey (CHNS) across 20 years of urbanization-related change. We then tested the association between the gut microbiota genera in 2015 with these intercepts and slopes in linear regression models, allowing for interactions between the intercepts and slopes. In the subset of the sample with metabolomic measures collected (n = 500), we then tested whether bacteria associated with change in diet (FDR corrected p-values < 0.05 from the joint test of both main effect and interaction) were associated with microbiome-related metabolites using linear regression models. Results: Controlling for current % calories from animal source food, we found 57 gut microbiota measures that were significantly associated with the rate of change in % animal source calories, with the majority (19%) coming from the order Clostridiales. For 55 gut microbiota measures, we found evidence that the association between current diet and gut microbiota was modified by the rate of change in diet. Thirty-two microbiome-related metabolites, over 50% of which were involved in the benzoate metabolism or food component pathways, were associated with these gut microbiota measures. Conclusions: Our findings suggest that long-term change in calories consumed from animal source foods may shape the composition of the gut microbial community. Further, our metabolome findings suggest that pathways linking diet and the microbiome through microbial metabolites may be particularly relevant.