Genetic Gut Microbiome Variations Point to Precision Treatments for Metabolic Conditions

In a new study, UCSF researchers found that the gut microbiome of East Asians is distinct from that of White individuals living in the same geographic region. This discovery may lead to personalized treatments for various metabolic conditions, including diabetes and obesity.

“We’re striving for a precision approach to optimizing metabolic health from a nutritional standpoint, tailored to each person’s specific biology,” said Suneil Koliwad, MD, PhD, chief of UCSF’s Division of Endocrinology and Metabolism and a senior author of the study. 

Genetic differences in gut microbiota may account for health disparities

In the U.S., East Asians often experience worse metabolic health outcomes compared to other ethnic groups at lower body mass indices. To determine if the gut microbiome plays a role in this disparity, Koliwad and the research team conducted a multi-omic study of 46 lean and obese East Asian and White participants living in the San Francisco Bay Area. They found notable differences in the bacterial richness and community structure of each group’s gut microbiome.

White individuals were enriched for the mucin-degrading Akkermansia muciniphila. East Asian subjects had increased levels of multiple bacterial phyla; fermentative pathways detected by metagenomics; and the short-chain fatty acid end-products acetate, propionate and isobutyrate.

“We used the demographic makeup of the San Francisco Bay Area to explore diverse responses to metabolic stimuli, including diet,” Koliwad said. “The East Asian individuals had a less diverse microbiome at every BMI compared to the White participants.”

Differences in the gut microbiota between the East Asian and White subjects were not related to dietary intake and were more prominent in lean individuals, but did correlate with the specific geographical location of the participants. The researchers transplanted microbiota from representative White and East Asian individuals into mice that lacked a microbiome of their own (germ-free mice). Remarkably, the differences between the gut microbiomes of White and East Asian participants persisted in the mice. When fed the same diet, the mice also gained different amounts of weight based on the ethnic identity of the microbial donor.

“The mouse models show that both the genetic makeup of the host and that person’s microbiome composition are determinants of how an individual gains and stores body fat,” Koliwad said.

Precision medicine for metabolic conditions

The study indicates that the gut microbiome is inherently different across genetically diverse populations. “Those differences have real physiological impacts on individuals,” Koliwad said. “A better understanding of the unique microbiome of different populations will lead to precision approaches to managing diabetes and obesity and optimizing nutrition and overall metabolic health.”

UCSF Medical Center is No. 6 in the nation for diabetes and endocrinology, according to U.S. News & World Report’s 2021-2022 Best Hospitals survey.

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