If you have a gut feeling something is preventing you from losing as much weight as you would like to, you could be right.

Researchers found that the gut microbiome — the bacteria that help digest food and absorb nutrients in the intestines — can influence attempts at weight loss.

They identified genes within these bacteria that determine how quickly the bacteria grow, how well people can take advantage of nutrients in food, and whether starches and fiber, in particular, get broken down into sugars too quickly to aid weight loss.

“Some people have a harder time losing weight than others,” study author Sean Gibbons, PhD, told Medscape Medical News. “For example, some people are able to control their weight through basic lifestyle interventions, while others may not.”

Dr Sean Gibbons

Furthermore, it is difficult to predict which individuals will respond to changes in diet or exercise and who might require more intense strategies.

The study, which was published online September 14 in mSystems, a journal of the American Society for Microbiology, could bring us closer to an answer.

“We’ve identified specific genetic signatures in the gut microbiome that were predictive of weight loss response in a small cohort of patients following a healthy lifestyle intervention,” explained Gibbons, Washington Research Foundation distinguished investigator and assistant professor at the Institute for Systems Biology in Seattle, Washington.

Weight Loss Takes Guts?

Differences in 31 functional genes emerged from the gut microbiome in 48 people who lost 1% or more of their weight each month compared with 57 others whose weight remained the same. These findings came from stool samples taken 6 to 12 months after people started a commercial weight loss coaching program.

In contrast, lead author Christian Diener, PhD, also of the Institute for Systems Biology, and colleagues found only one factor in the blood that differed between the weight loss and weight maintenance groups. (They specifically evaluated proteins associated with obesity in the blood and genetic data from stool samples in a subset of 25 participants.)

Dr Hana Kahleova

Their findings align with previous research showing different types of bacteria in the gut microbiome can affect the success of weight loss interventions, but they took it a step further to determine how this works.

“We know that the gut microbiome plays an important role in weight management and can also influence a response to weight loss interventions. However, specific gut microbiome features that can explain this observation in more detail are still to be discovered,” Hana Kahleova, MD, PhD, MBA, director of clinical research at the Physicians Committee for Responsible Medicine in Washington, DC, told Medscape Medical News when asked for comment.

Good vs Bad Players

On the plus side, genes that help bacteria grow more rapidly were associated with weight loss. These bacteria take more of the nutrients in food for themselves, leaving less to go toward human weight gain compared with slower growing bacteria.

In fact, prior evidence points to a particular gut bacteria, Prevotella, as being beneficial for weight loss. “In our study,” Gibbons said, “we found that some of the fastest-growing microbes in the weight-loss responder group were from the genus Prevotella.”

On the other hand, bacteria that produce more enzymes to breakdown starches or fiber quickly into sugars, for example, were linked with making people more resistant to weight loss.

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

Kahleova agreed. “These findings expand our understanding of the specific features of the gut microbiome that play a role in weight loss,” she said.

Moving Beyond BMI

Interestingly, the researchers controlled for baseline body mass index (BMI) and other factors that could affect weight loss. People who start off with a higher BMI tend to lose more weight than others, a phenomenon known as ‘regression to the mean.” This factor confounded some earlier research, they noted.

“The vast majority of features associated with weight loss, independent of BMI, were functional genes within the gut metagenome,” Gibbons said.

“This tells us that the gut microbiome is an important modulator of weight loss, independent of your underlying metabolic health state, baseline diet, or BMI status.”

Gibbons shared his findings, including the predominant role played by gut microbiome, via Twitter.

“This study described several metagenomic functional features that were associated with weight loss after controlling for potential confounders, such as age, sex, and baseline BMI,” Kahleova said. “These findings…may help optimize the weight-loss protocols in future studies.”

Fecal Microbiota Transplants?

What do the findings mean for people willing to adjust their diet — or undergo a fecal transplant — to include more of the gut bacteria that facilitate weight loss?

It could be too soon for such interventions, Gibbons said. “It is still very difficult to rationally engineer your gut microbiome.”

“Interestingly, a recent study suggests that fecal transplants from a high-Prevotella donor may be able to flip low-Prevotella recipients to high-Prevotella,” Gibbons said.

More research is required, however, to understand whether or not these fecal microbial transplant-flipped individuals are also more capable of weight loss, he added.

Beyond that, “I can’t give any specific recommendations, other than that [people] should eat more fiber-rich, plant-based, whole foods and reduce their consumption of red meat. That’s well-supported.”

“Also, prepare your own meals, rather than relying on sugar and sodium-rich processed foods,” Gibbons said.

Gibbons and his team hope to validate their work in larger human studies “and perhaps develop clinical diagnostics or interventions for people trying to lose weight.”

mSystems. Published online September 14, 2021. Full text

Damian McNamara is a staff journalist based in Miami. He covers a wide range of medical specialties, including infectious diseases, gastroenterology, and critical care. Follow Damian on Twitter: @MedReporter.

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