Over the course of this project, we sought to identify novel microbiome-derived risk factors that improve upon current methods for predicting an individual’s likelihood of developing specific conditions over the next 5–10 years. To accomplish this, we recruited and profiled over 3,000 new individuals (as well as additional disease cohorts) and combined these with a previously assembled cohort of more than 2,200 participants. In total, we collected clinical data and gut microbiome samples, and banked blood and stool from all these individuals. Leveraging these resources, we developed new experimental and computational techniques to deeply characterize microbial gene functions, microbiome-produced metabolites, and the interplay between gut microbes and the host immune system. These collective efforts have led to 57 publications stemming from this grant.
Notably, we uncovered several microbiome-related risk factors across different health domains. For example, in a large-scale population study integrating continuous glucose monitoring, body composition scans, and liver ultrasound data, we found 145 bacterial pathways—including purine ribonucleosides degradation—that consistently correlated with host metabolic markers such as BMI, liver health, and Type-2 Diabetes risk. In another study, we discovered over 1,300 bacterial SNPs significantly linked to BMI, highlighting previously underexplored species and shedding light on potential mechanisms like inflammatory pathways in Bilophila wadsworthia and energy metabolism in Faecalibacterium prausnitzii. Importantly, many of these associations persisted after controlling for diet, medication use, and physical activity.
Additional analyses also demonstrated that gut microbiome pathways and dietary patterns can predict clinical features of sleep apnea—such as daytime sleepiness—more accurately than traditional predictors like age, BMI, or visceral adipose tissue alone, reinforcing the microbiome’s robust influence on multiple facets of human health. In parallel, we have shown how lifestyle factors shape more than half of various sleep parameters, further underscoring the interplay between the microbiome, host physiology, and everyday behavior. Overall, our work has advanced the understanding of how gut microbial composition and genetics intersect with human metabolic and clinical outcomes. We anticipate that these discoveries will pave the way for microbiome-based biomarkers and targeted interventions, offering new avenues for disease prevention and personalized healthcare.
