Could the study of gut microbiota lead to a non-surgical treatment for morbid obesity?

Morbid obesity

The health of individuals with a body mass index (BMI) of 30 or higher is severely at risk, yet the therapeutic options for addressing obesity are limited. Bariatric surgery, though invasive, is a very, some says the most, effective known treatment for people with morbid obesity, i.e. a BMI of 40 and higher.

Different bariatric surgery procedures exist, including Roux-en-Y gastric bypass (RYGB) and vertical banded gastroplasty (VBG, or ‘stomach stapling’); what they all have in common is that they physically alter the digestive tract and induce weight loss. Bariatric surgery works around 80% of the time to help patients lose weight for the long term, according to most estimates.

Surgeons carry out these procedures because they work – but how exactly do they work? Originally, researchers thought that reconfiguring the digestive tract affected weight loss by limiting the amount a person can eat, by reducing absorption of nutrients, or both. But over time, they have realized this simple account doesn’t fully explain the mechanics of how the surgery induces weight loss.

A study from 2013 gave the first big clue that the gut microbiota could be helping cause the weight loss in these surgery patients. First of all, it showed (in agreement with previous studies) that RYGB restructured the microbiota of the gastrointestinal tract in rats, mice, and humans alike. Mice who got a sham surgery, for example, didn’t show changes in their gut microbiota in the same way. Researchers saw certain bacterial groups increase after RYGB: Gammaproteobacteria and Verrucomicrobia. But what sealed the deal was this – when researchers took the gut microbiota from a mouse that had undergone RYGB and transferred it to a germ-free mouse that had never had surgery, the recipient mouse lost weight. This showed that something about the post-RYGB gut microbiota – not necessarily the surgery itself – could help the mouse slim down.

A study from 2015 confirmed that the gut microbiota’s connection to weight loss after bariatric surgery is true for humans and persists for at least a decade. Researchers studied a group of women who’d had bariatric surgery – either RYGB or VBG – to treat obesity about a decade ago, and who had maintained a lower weight ever since. These women still showed changes in the composition and function of their gut microbiota, compared to before their surgery. In terms of function, the new microbiota produced different quantities of some compounds important in metabolic health, and the bacteria lowered their use of carbohydrates as fuel.

This evidence shows that a stable post-surgery weight, even in the long term, is associated with gut microbiota changes. What could it be about the microbiota after bariatric surgery that gives it the power to help people lose weight?

The post-surgery microbiota is still a black box, but scientists are urgently trying to discover how it works. Knowing how the microbiota shifts to induce weight loss, and how to make this new microbial community ‘stick’ in people who don’t have surgery, could revolutionize obesity treatment.

We know that fecal microbiota transplantation (FMT) from a lean donor to an obese recipient cannot make weight loss happen: FMT does not change the microbiota long-term in humans with metabolic disease. This branch of study still could lead somewhere, though, since scientists observed that both fecal and small intestinal gut microbiota were changed immediately after an overweight patient received FMT, and most of the changed bacteria were those that produced beneficial molecules called short-chain fatty acids. The next task is to ‘mine’ the fecal samples for new probiotic bacteria that could take credit for any beneficial effects on metabolism, and try delivering these specialized bacteria to those who want to reduce their weight. We might not know the names of these bacteria yet, but they could one day unlock the secret to a lasting treatment for obesity that requires no surgery.

 

 

References:

Bakker GJ, et al. (2015) Gut Microbiota and Energy Expenditure in Health and Obesity. Journal of Clinical Gastroenterology 49, S13-S19 doi: 10.1097/MCG.0000000000000363

 

Liou AP, et al. (2013) Conserved Shifts in the Gut Microbiota Due to Gastric Bypass Reduce Host Weight and Adiposity. Science Translational Medicine 5(178) doi:  10.1126/scitranslmed.3005687

 

Tremaroli V, et al. (2015) Roux-en-Y Gastric Bypass and Vertical Banded Gastroplasty Induce Long-Term Changes on the Human Gut Microbiome Contributing to Fat Mass Regulation. 22(2), 228-238 DOI: http://dx.doi.org/10.1016/j.cmet.2015.07.009

Kristina Campbell
Kristina Campbell
Science writer Kristina Campbell (M.Sc.), from British Columbia (Canada), specializes in communicating about the gut microbiota, digestive health, and nutrition. Author of the best selling Well-Fed Microbiome Cookbook, her freelance work has appeared in publications around the world. Kristina joined the Gut Microbiota for Health publishing team in 2014.  Find her on: GoogleTwitter