Postdoctoral Fellowship: PRFB: Elucidating the chemical potential of the small intestinal microbiome

This action funds an NSF Postdoctoral Research Fellowship in Biology for FY 2025. The fellowship supports research and training of the fellow that will contribute to biology in innovative ways. Despite the numerous known associations between the human gut microbiome and health or disease, progress towards establishing what causes these outcomes has been slow.

Most microbiome studies focus on analyzing feces, which allows analysis of the large intestinal microbiome. However, there is a knowledge gap about the microbiome in the small intestine (SI), which is a site of important host–microbe interactions. This project will probe how individual SI microbes and SI microbial communities respond to stressful host factors and protect against pathogens.

Results will increase basic biological knowledge that may aid in developing effective microbiome-targeted therapies. The fellow will engage in public outreach, including writing blog posts and developing a strategy card game to enable students to learn core ecological principles in informal settings.

This research will capitalize on a novel capsule device that non-invasively samples both chemicals and viable microbes across the entire gastrointestinal tract, including the SI. In addition to characterizing the bulk microbial composition using next-generation DNA sequencing, the fellow will isolate SI microbes to generate a diverse strain collection.

Using high-throughput in vitro growth assays, the fellow will quantify how different oxygen tensions and bile acids, which participate in digestion, impact microbial growth. Liquid chromatography mass spectrometry will be used to elucidate how supplemented bile acids are chemically transformed by the microbes. Both top-down undefined and bottom-up synthetic microbial communities will be constructed to probe the emergent effects of bile acid metabolism as well as their colonization-resistance potential against SI pathogens isolated from patients diagnosed with small intestinal bacterial overgrowth (SIBO).

Collectively, these studies will enhance mechanistic understanding for the interplay among the SI, distal GI tract, and host. By exploiting large-scale in vitro growth data, this work will derive fundamental principles that predict in vivo microbial behavior. In performing this research, the fellow will receive training in microbial isolation and culturing, next-generation sequencing, and large-scale data analysis.

The fellow will train and mentor undergraduate students to use interdisciplinary approaches to investigate the gut microbiome across molecular, organismal, and host scales.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.