Role of gut microbiota in obesity and the future of microbiota therapeutics for obesity

Feb. 12, 2022

In an article published in Expert Review of Gastroenterology and Hepatology in 2021, co-authors Kanika Sehgal, M.B.B.S., and Sahil Khanna, M.B.B.S., M.S., summarize the pathogenesis of obesity, the relationship between the gut microbiota and obesity, and the future of microbiota-based therapies in obesity management. Dr. Sehgal is a Mayo Clinic gastroenterology research fellow and Dr. Khanna is a gastroenterologist who leads the clinical and research program involving fecal microbiota transplantation (FMT) for Clostridium difficile infection at Mayo Clinic in Rochester, Minnesota.

In this Q and A, Drs. Sehgal and Khanna highlight some of the significant points presented in their review article exploring the current status of research related to microbiota therapeutics for obesity.

What prompted your interest in this vein of research? Why is it important for gastroenterologists to expand their knowledge in this topic now?

The prevalence of obesity continues to rise at alarming rates. Due to its chronic and relapsing nature, management of this condition remains a challenge. While its pathogenesis is known to be multipronged — with the involvement of diet, lifestyle and genetics — recent studies have suggested that gut microbiota may play a role in causing obesity.

Building on the suspected association of gut microbiota with obesity, researchers hypothesize that it might be possible to harness microbial therapies to treat this condition, as a supplement to existing standards of care. Studies examining microbiota-based therapies, such as FMT, have illustrated beneficial effects on the metabolic profile of recipients. With evolving research, if FMT proves to be advantageous, we believe that its effectiveness in microbial restoration could mean that it can potentially be used as an adjunctive treatment for obesity.

Did you have any commonly held assumptions related to this research topic or the diagnosis that you wished to confirm or validate with your review?

Researchers conducting animal studies were the first to demonstrate an association between gut microbiota and obesity. Findings from these widely known studies suggested that microbiota transfer from obese mice to germ-free mice led to an increase in weight. These studies also attempted to establish differences in the gut microbiome of obese and lean mice. Notably, mice that became obese had an increase in Firmicutes and a decrease in Bacteroidetes; in contrast, lean mice had an increase in Bacteroidetes and a decrease in Firmicutes.

Eventually these findings led researchers to consider that human studies might yield similar results. However, early exploration of this hypothesis revealed that the association between gut microbiota and obesity might not be as simplistic as initially perceived. Further animal studies have found conflicting evidence, showing that a relative increase in the number of Firmicutes to Bacteroidetes, or an increase in the Firmicutes-to-Bacteroidetes ratio, is not associated with an increase in body weight.

Results in human studies were also largely inconsistent. It seems that the relative composition of Firmicutes and Bacteroidetes, as well as the overall gut microbial composition, depends on a plethora of factors including, but not limited to, diet composition, energy content, fasting and eating patterns, and the use of prebiotics, probiotics and antibiotics.

Did your literature review reveal anything unexpected or surprising or highlight a specific gap that future research should address?

While there seems to be a relationship between gastrointestinal microbiota and the human metabolic profile, data derived from human studies remain inconsistent. The direct physiological effect of gut microbiota on weight needs to be exhaustively studied. Human investigations are needed to evaluate the effect of diet and activity and their interaction with host genetics along with the possible effect on the gut microbiome. Furthermore, we need to learn more about the specific strains of bacteria that might be directly involved. Microbial restoration therapies such as FMT are currently being investigated as an adjunctive treatment. However, details related to the use of FMT in the clinical setting, such as dose frequency, timing of dose and donor matching, also would need further exploration.

For more information

Sehgal K, et al. Gut microbiota: A target for intervention in obesity. Expert Review of Gastroenterology and Hepatology. 2021;15:1169.

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