April 15, 2013

Gut Microbes Affect Weight After Gastric Bypass

A gut microbe. A gut microbe.David Gregory and Debbie Marshall. All rights reserved by Wellcome Images.

A study in mice suggests that gastric bypass surgery may result in weight loss in part by altering microbes in the gut. The finding may lead to a better understanding of how microbes influence energy balance.

Gastric bypass is a type of surgery used to treat severe obesity. In a procedure known as Roux-en-Y gastric bypass (RYGB), part of the stomach and small intestine are removed. The procedure results in significant weight loss as well as improvements in associated conditions such as type 2 diabetes. Decreased calories, however, can’t fully account for all these effects.

The digestive tract is home to trillions of microbes, both helpful and harmful, that outnumber the body’s cells by 10 to 1. A team of researchers led by Dr. Alice P. Liou and Dr. Lee M. Kaplan from Massachusetts General Hospital and Dr. Peter J. Turnbaugh from Harvard University wondered whether some of the benefits of RYGB surgery might come from changes in digestive tract microbes.

To investigate, the researchers performed RYGB surgery or sham surgery on obese mice. The work was funded in part by NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of General Medical Sciences (NIGMS). Some of the mice that had sham surgery were given a restricted diet so their weight would match the weight of those that underwent RYGB surgery.

To assess the types of microbes found in the animals' guts, the team sequenced and compared 16S ribosomal RNA (rRNA) genes from mouse fecal samples collected over 12 weeks. A central component of the protein-manufacturing machinery of all living cells, rRNA is often used as a marker to identify different bacteria.

The researchers reported in the March 27, 2013, issue of Science Translational Medicine that mice that underwent RYGB surgery lost 29% of their body weight within 3 weeks. This was accompanied by a decrease in fat mass despite no change in net food intake. The RYGB surgery resulted in a marked change in the composition of microbes in the gut, with changes seen as early as a week after surgery. Alterations seen throughout the entire digestive tract were similar to those previously reported in humans and rats.

The researchers next performed a series of “fecal transplants.” They collected samples of gut microbial communities from mice that had undergone gastric bypass, sham surgery, or sham surgery plus restricted diet. The samples were put into the stomachs of lean mice that were germ free and thus had no preexisting gut microbial communities.

The mice that received microbes from the RYGB surgery mice lost weight and had less fat mass than mice that received microbes from either group of sham surgery mice. The mice that received the RYGB-mouse microbes had a food intake similar to mice that remained germ free.

This research shows that the beneficial effects of RYGB surgery are due in part to changes in the gut microbial community. “Our findings emphasize the importance of accounting for the influence of the trillions of microbes that inhabit our body when we consider obesity and other complex diseases,” Turnbaugh says.

— by Carol Torgan, Ph.D.

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References: Sci Transl Med. 2013 Mar 27;5(178):178ra41. doi: 10.1126/scitranslmed.3005687. PMID: 23536013.

Funding: NIH’s National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and National Institute of General Medical Sciences (NIGMS), Harvard Digestive Diseases Center, and Ethicon Surgical Care.