Study reveals how gut bacteria and diet can reprogram fat to burn more energy

(Press-News.org) LOS ANGELES — Scientists at City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the U.S. and a leading research center for diabetes, the Broad Institute and Keio University have discovered how specific gut bacteria work together with diet to flip a metabolic switch — transforming energy‑storing white fat into calorie‑burning beige fat in mice. 

The study, published today in Nature, shows that a low‑protein diet activates a precise set of gut microbes that send chemical signals throughout the body, prompting fat tissue to burn energy instead of storing it. The findings uncover a previously unknown biological pathway linking diet, the gut microbiome and metabolic health — one that could eventually inform new treatments for obesity, diabetes and related diseases. 

“Fat tissue is not fixed — it’s surprisingly adaptable,” said Kenya Honda, M.D., Ph.D., co‑senior author of the study and adjunct professor at City of Hope. “We found that certain gut bacteria can sense what the host is eating and translate that information into signals that tell fat cells to burn energy.” 

Most adult body fat consists of white fat, which stores excess calories. In contrast, beige and brown fat burn energy to generate heat and help regulate metabolism. Babies are born with significant amounts of brown fat, but those stores decline with age. For years scientists have searched for safe ways to convert white fat into beige fat — a process known as “beiging” — as a potential strategy to improve metabolic health. 

In this study, researchers from City of Hope, Keio University and the Broad Institute found that mice fed a low‑protein diet developed large amounts of beige fat only if they had the right gut bacteria. When the same diet was given to germ‑free mice with no microbiome, the fat‑burning effect disappeared. 

“This told us the diet alone wasn’t enough,” Honda said. “The gut microbiome was essential.” 

The researchers identified four specific bacterial strains that were required to trigger fat browning. When these microbes were introduced into mice alongside a low‑protein diet, the animals converted white fat into beige fat, gained less weight, showed improved glucose control and had lower cholesterol levels. 

Rather than flipping a single switch in fat tissue, the gut bacteria acted more like a relay team. They sent one signal that changed bile acids and nudged fat cells toward a calorie burning state and a second signal that caused the liver to release a metabolism boosting hormone called FGF21. When scientists interrupted either signal, the fat burning effect disappeared — revealing that the two signals must work together for the process to succeed. 

“This work underscores how the gut microbiome is actively interpreting what we eat and translating that information into signals the body responds to,” said co-senior author Ramnik Xavier, M.D., Ph.D., a core member at the Broad Institute and professor of medicine at Harvard Medical School. “This opens up an opportunity to think about the interactions between microbes, metabolites and metabolic disease, understand the mechanisms, and potentially translate that into interventions for metabolic health.” 

The researchers emphasize that the findings should not be directly applied to people. The low‑protein diet used in the study is lower than what is recommended for humans, and previous attempts to improve metabolism by giving people probiotics alone have largely failed. 

Instead, the work points to new drug targets — the biological pathways activated by microbes — rather than extreme diets or bacterial supplements. 

“Our goal is not to tell people to eat extreme diets,” said study first author Takeshi Tanoue of City of Hope and Keio University. “The real opportunity is to understand these pathways well enough to design therapies that safely mimic their benefits.” 

Obesity and metabolic disease are major risk factors for cancer, diabetes and cardiovascular disease — areas where City of Hope has deep expertise. By revealing how gut microbes and diet reshape fat tissue, the study adds to a growing understanding of how metabolism, inflammation and disease risk are biologically connected. This research is part of the Microbiome Program at City of Hope, which is revolutionizing cancer care through a nexus of personalized and holistic medicine, integrating diet, nutrition and the immune system to promote early detection, personalized interventions and better treatment outcomes. 

“This work highlights the gut microbiome as an active decision‑maker in the body,” Honda said. “It doesn’t just respond to diet — it interprets it.” 

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The study, “Microbiota‑mediated induction of beige adipocytes in response to dietary cues,” was supported by the Japan Agency for Medical Research and Development, the Japan Society for the Promotion of Science, Stand Up to Cancer, the Wellcome Trust and Temasek Trust, the Mitsukoshi Health and Welfare Foundation, Chugai Foundation for Innovative Drug Discovery Science, Keio University, the Infectious Disease and Microbiome Program at the Broad Institute, and the National Institutes of Health. 

About City of Hope 
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked among the nation’s top cancer centers by U.S. News & World Report at its core, City of Hope’s uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope’s growing national system includes its Los Angeles campus, Orange County, California, campus, a network of clinical care locations across Southern California and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope’s affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.   

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