Uncovering how protists shape GUT microbiome function and community structure

The National Institute of Allergy and Infectious Diseases awarded Georgia TECH Research Corp $152,600 on December 9, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to investigate how Blastocystis, the most prevalent protist in the human gut microbiome, shapes gut ecosystem function and community structure.

The research comprises three aims. Aim 1 examines how Blastocystis metabolizes dietary lipids through biochemical assays, microscopy-based trafficking analysis, and transcriptomic identification of genes involved in lipid transport and metabolism, building on preliminary evidence that lipid-rich conditions promote growth and that people colonized with Blastocystis have lower serum triglyceride levels. Aim 2 investigates how Blastocystis modulates microbiome composition by releasing metabolic byproducts—specifically succinate and hydrogen—through quantification of metabolite production, microbial response testing, and targeted metabolomics to identify cross-feeding relationships. Aim 3 explores cooperative and competitive interactions between Blastocystis and saccharolytic bacteria, including fiber-degrading specialists and generalists, using co-culture experiments and microcosms to assess microbial fitness and metabolite exchange.

Performance occurs in Atlanta, Georgia, with a period of performance through August 31, 2029. The assistance type is a Project Grant.

Abstract

Blastocystis is the most prevalent protist in the human GUT microbiome and is frequently associated with improved GUT and cardiometabolic health. Despite these associations, the biology of blastocystis and its mechanistic role in the GUT environment remain poorly understood. This project investigates the fundamental biology of blastocystis to understand how its metabolism and interactions with other microbes shape the GUT ecosystem. Aim 1 examines how blastocystis metabolizes dietary lipids. People colonized with blastocystis have lower serum triglyceride levels, and preliminary evidence shows that lipid-rich media promotes growth and increases cell size, suggesting blastocystis has a lipophilic metabolism that may influence host health. This aim will quantify lipid uptake through biochemical assays, trafficking using microscopy, and will identify genes involved in lipid transport and metabolism through transcriptomic analysis. Aim 2 investigates how blastocystis modulates microbiome composition through the release of metabolic byproducts. Blastocystis correlates with an enrichment of succinate and hydrogen metabolizing microbes, and blastocystis is predicted to produce both metabolites. This aim will quantify metabolite production, test microbial responses to blastocystis-derived metabolites, and apply targeted metabolomics to identify cross-feeding between blastocystis and associated microbes. Aim 3 explores how blastocystis cooperates or competes with saccharolytic bacteria. Blastocystis positively correlates with fiber degrading specialists (e.g. ruminococcus champanellensis) and CO-excludes saccharolytic generalists (e.g. bacteroides fragilis), indicating that blastocystis engages in cooperative and competitive interactions that influence community structure. CO- culture experiments and microcosms will assess microbial fitness and metabolite exchange, supported by untargeted metabolomics and transcriptomics. This proposal integrates microbial cell biology, transcriptomics and metabolomics to provide a mechanistic understanding of how a protist contributes to GUT microbiome community structure and function. These findings will advance foundational knowledge of host-associated protists and reveal principles of protist driven interactions in the human GUT ecosystem.