Diet, microbes, and metabolic adaptation
White adipose tissue stores energy, while brown and beige fat burn energy through thermogenesis. Under certain environmental conditions, white fat can transition into beige fat in a process known as browning. This transformation increases energy expenditure potentially influencing metabolic health and aiding in weight management
It has been previously shown that low protein diets can stimulate this browning process, however, this current research has showed that this metabolic shift is largely microbiome dependent, and identified the microbial pathways responsible for transmitting dietary signals to the host.
One of these microbial pathways involved gut bacteria modifying bile acids, molecules that have a large role in regulating metabolism. These microbially modified bile acids activate a receptor called FXR in adipose progenitor cells, promoting the development of beige fat cells. A second pathway involved microbial nitrogen metabolism, where certain bacteria produce ammonia that travels to the liver and stimulates the production of the metabolic hormone FGF21, which in turn, helps drive adipose beiging. Together, these signals promote sympathetic nervous system activity, and ultimately, trigger the adipose response.
Identifying the microbes responsible
To pinpoint the microbes involved, this international research team used gnotobiotic mouse models and microbial culture approaches developed at Bio2Q. By isolating bacterial strains from both mice and humans, the researchers were able to identify the minimal microbial consortia capable of triggering the browning response during low-protein feeding.
Using human microbiota samples, it was shown that the browning response requires two groups of bacteria working together, four ammonia-producing strains and five bile-acid-modifying strains, and together, these functions generated the signals needed to induce the fat-burning program.
When germ free mice received these bacterial consortiums and were then placed on a low-protein diet, they showed increased beige fat formation, higher expression of thermogenic genes, improved glucose metabolism, and reduced circulating lipids.
A microbial framework for dietary sensing
These findings suggest that gut microbes serve as an important and active interface between diet and host physiology, mediating changes in nutrient availability, and turning that change into hormonal and metabolic signals.
As a number of microbes are needed to drive this metabolic outcome, as long as they carried the key functional activities required to drive the response, these findings suggest that microbial metabolism, rather than the presence of specific bacterial species, may be the critical factor shaping diet–microbiome interactions overall. Understanding these relationships could help researchers design microbial therapies that improve metabolic health or strengthen the effects of dietary interventions.
About WPI-Bio2Q
The Human Biology Microbiome Quantum Research Center (WPI-Bio2Q) at Keio University is an international research center focused on understanding how microbial communities interact with human biology. By integrating microbiology, immunology, systems biology, and computational science, Bio2Q researchers investigate how the microbiome shapes metabolism, immunity, and disease, with the goal of translating these discoveries into new diagnostics and therapies.
