Gut Reaction: Understanding the Microbiome

New insights from the Hooper lab could harness the power of commensal gut bacteria.

Living harmoniously inside the intestines of humans and other mammals are hundreds of trillions of microbial cells. Decades ago, scientists discovered that these microbes improve the efficiency of digestion. Over the last 20 years, research led by Lora Hooper, Ph.D., Professor and Chair of Immunology at UT Southwestern Medical Center, has shown that this vast population of commensal organisms does far more than assist in digestion. Her research has revealed that these microscopic assistants also play key roles in regulating the immune system and the circadian clock.

Dr. Hooper, who also serves as Professor of Microbiology and is part of the Center for Genetics of Host Defense, explains that these findings answer fundamental questions about how mammalian biology has come to depend on microbes.

Pivotal Insights

Dr. Hooper joined UT Southwestern after a postdoctoral fellowship at Washington University School of Medicine in St. Louis with Jeffrey Gordon, M.D., a professor of pathology and immunology who is widely considered the father of the field of gut microbiome research. There, she became intrigued with the precarious balance that gut microbes have with their host organisms.

After she established her lab at UT Southwestern in 2003, Dr. Hooper’s initial experiments focused on how the gut microbiome affected gene expression in intestinal cells. In 2008, she was named a Howard Hughes Medical Institute Investigator.

One pivotal finding stemming from this early work is that gut microbes interact with intestinal cells to regulate the circadian clock. In 2021, she and her colleagues reported in Cell that the amount of natural compounds produced by the intestines to fight foodborne infection changes depending on the time of day, a phenomenon driven by an interplay between intestinal cells and gut bacteria.

Another finding spurred by these initial experiments is that gut microbes regulate the absorption of dietary lipids. In a recent paper on this topic, published in Science in 2023, she and her colleagues showed that a gene called Snhg9 becomes less active in intestinal cells in the presence of intestinal bacteria, a process that increases the amount of lipids taken up by the intestines.

“Lora is a very big-picture thinker,” says Gabriella Quinn, a graduate student researcher in the Hooper lab and in UTSW’s Perot Family Scholars Medical Scientist Training Program. “She encourages us to think about things like, why would this system have evolved this way? What advantages are there to the host?”

Today, the Hooper lab is investigating how the microbiome might be involved in extracting the lipid vitamin A from food and delivering it to immune cells that need this nutrient to develop.

Looking Ahead

Collaborations are taking the Hooper lab in new directions, says Andrew Y. Koh, M.D., Professor of Pediatrics, of Microbiology and in the Harold C. Simmons Comprehensive Cancer Center. Drs. Koh and Hooper have three ongoing collaborative projects: one to investigate how Candida yeast colonizes the gut, a phenomenon that can cause fatal yeast infections in cancer and stem cell transplant recipients; one to study how vitamin A influences adaptive immune regulation; and one examining how the circadian clock modulates the response to cancer immunotherapy.

Every piece of research adds new insight into the gut microbiome, a field that has taken off over the course of Dr. Hooper’s career.

“The microbiome is incredibly complex,” says Dr. Hooper, member of the National Academy of Sciences (2015) and the National Academy of Medicine (2022). “It’s different in every single person, and it’s incredibly difficult to study. But our understanding of it has enormous potential to promote human health.”

Lora Hooper, Ph.D., Professor and Chair of Immunology, Professor of Microbiology and in the Center for the Genetics of Host Defense

Andrew Y. Koh, M.D., Professor of Pediatrics, of Microbiology and in the Harold C. Simmons Comprehensive Cancer Center

Gabriella Quinn, graduate student in the Hooper lab and in UTSW’s Perot Family Scholars Medical Scientist Training Program