Gut microbiome makeup can determine ability to lose weight

The trillions of bacteria living in the human digestive tract may play a decisive role in determining whether an individual can successfully lose weight, according to research published this week in mSystems, a journal of the American Society for Microbiology.

Researchers at the Institute for Systems Biology in Seattle identified specific genetic signatures in the gut microbiome that were predictive of weight loss response in a cohort of individuals participating in a commercial wellness program.

The study focused on 105 participants: 48 individuals who lost more than 1% of their body weight per month over six to 12 months, and 57 individuals who maintained a stable body mass index over the same period. Rather than prescribing a specific diet, the program offered coaching and advice from a dietitian and a nurse.

After controlling for age, sex and baseline BMI, researchers identified 31 baseline stool metagenomic functional features associated with weight loss responses. These included complex polysaccharide and protein degradation genes, stress-response genes, respiration-related genes, cell wall synthesis genes and gut bacterial replication rates.

Key findings

A major finding was that the gut microbiome of individuals who did not lose weight was more efficient at breaking down and absorbing carbohydrates. These bacteria produced more enzymes to dismantle starches and fiber into digestible sugars, potentially leaving more calories available for the body to absorb.

Conversely, individuals who lost weight had increased numbers of genes that speed up bacterial growth and replication. Faster-growing bacteria consume more nutrients for themselves, leaving fewer calories available for human weight gain.

“Before this study, we knew the composition of bacteria in the gut was different in obese people than in people who were nonobese, but now we have seen that there is a different set of genes that are encoded in the bacteria in our gut that also responds to weight loss interventions,” said lead study author Christian Diener, a research scientist at the Institute for Systems Biology.

Implications for weight loss

“Your gut microbiome can help or cause resistance to weight loss, and this opens up the possibility to try to alter the gut microbiome to impact weight loss,” Diener said.

Sean Gibbons, assistant professor at the Institute for Systems Biology and a study author, said the work may lead to diagnostics for identifying individuals likely to respond to mild lifestyle interventions versus those who may need more intensive approaches.

“By understanding these functional patterns, we may one day be able to engineer resistant microbiomes to be more permissive to weight loss,” Gibbons said.

Context and limitations

The study is the latest in a line of inquiry dating to the 1980s, when research began to hint at a link between obesity and gut microbiome composition. The completion of the Human Genome Project in 2003 gave researchers molecular-level tools to study the trillions of microbes that inhabit the human body.

While the findings are promising, researchers caution that the science is not yet advanced enough to prescribe specific microbiome-altering interventions for weight loss. A variety of factors influence weight, and the gut is not the only variable.

For now, experts recommend focusing on foods and behaviors that contribute to overall gut health: eating fresh fruit, vegetables, leafy greens and naturally fermented foods; avoiding stress; getting adequate sleep; and exercising regularly.

“The gut microbiome is a major player in modulating whether a weight loss intervention will have success or not,” Diener said. “The factors that dictate obesity versus nonobesity are not the same factors that dictate whether you will lose weight on a lifestyle intervention.”