Huang Lab Studying Human Gut Bacteria in New NIH Grant

By Dirk Hoffman

Yolanda Huang, PhD, assistant professor in the Department of Microbiology and Immunology, is principal investigator on a five-year, $2.17 million grant from the National Institute of General Medical Sciences (NIGMS), titled “Polysaccharide Utilization and Antimicrobial Resistance in Abundant Gut Bacteria.”

The award represents the first NIH grant for Huang’s lab. She joined the Jacobs School in 2023 from the Lawrence Berkeley National Laboratory where she worked as an Astellas Pharma awardee of the Life Sciences Research Foundation postdoctoral fellowship.

The laboratory is a U.S. Department of Energy Office of Science national laboratory managed by the University of California. There, she developed a novel high-throughput functional genomic approach to study gut bacteria.

“Receiving my first major NIH grant is a major milestone as a new PI,” Huang says. “I am grateful and excited our research is recognized as high impact and important for funding. This allows me to focus on pursuing exciting research in the next few years.”

The NIGMS award is an R35 grant classified as a Maximizing Investigators’ Research Award (MIRA).

“The MIRA grant is unique among NIH grants as it funds the research program of the lab and not specific projects,” Huang explains. “This flexibility allows room for creativity, productivity and impactful breakthroughs.”

Gut bacteria play a vital role in human health, Huang says, noting the overarching vision of her lab’s research is to advance its mechanistic knowledge of how microbes colonize, grow, and survive in the human gut.

The researchers’ long-term goal is to use their mechanistic findings to develop strategies to manipulate microbiota composition and function for health benefits.

“The microbial communities in our gut are highly diverse and most of their biology remain understudied,” she says. “This makes it difficult to develop strategies to manipulate the gut microbiota for health applications.”

Researchers in Huang’s lab study a highly abundant and prevalent group of bacteria in the human gut called Bacteroidales, a vital group that significantly contribute to overall health by maintaining gut balance.

While these bacteria are mostly beneficial for human health, they can also be pathogenic and found in chronic wounds, abscesses, and gut inflammation, Huang says.

A critical function of the gut microbiota is to provide colonization resistance to prevent invasion from pathogens like Salmonella.

“We are interested in understanding why they are so successful at colonizing the gut habitat from a mechanistic perspective,” Huang says.

“The colon is an anoxic environment and Bacteroidales are strict anaerobes (microbes that do not grow in the presence of oxygen), so we grow and study these bacteria in anaerobic chambers,” she adds. “We are using cutting-edge functional genomic platforms to discover new biology of Bacteroidales in a high-throughput manner.”

“By combining DNA barcoded overexpression libraries, selection-based screens, and targeted experiments, we can directly link genetic determinants to bacterial traits like nutrient utilization and stress tolerance,” says Kamrul Hasan, PhD, a postdoctoral associate in the Huang Lab involved with the work.

The research aims to generate an atlas of pathways encoded among Bacteroidales that are important for polysaccharide utilization and tolerance to antimicrobials.

“Bacteroidales use a broad range of glycans as nutrients, such as mucin and dietary fibers. We are interested in answering the question of how they accomplish this,” Huang notes.

“This will allow us to better understand how the nutrient landscape and our diet drive microbiota compositions,” she adds. “Potential applications include prebiotic and probiotic development, and dietary interventions to enhance beneficial bacteria in the gut to alleviate symptoms.”

Because the human gut is under constant flux and bacteria have evolved diverse strategies to tolerate common stressors, another aim of the grant is to study resistance mechanisms against antimicrobials, including antibiotic and human-target drugs that alter gut microbiota composition. This research is led by Allison Hanna, a student in the doctoral program in microbiology and immunology.

Nearly 60% of adults in the U.S. use daily oral medications to manage conditions like diabetes, heart disease, anxiety, and chronic pain. These frequently prescribed oral medications often perturb the gut microbiota, but it is not well understood how they kill gut commensals. Hanna is hoping to uncover the specific mechanisms involved.

“Our work will help identify novel targets for antibiotic development and improve current medications to reduce collateral disruption of beneficial gut microbes,” Hanna says.