Fighting obesity with gut bacteria

By Reuters Staff

NEW YORK (Reuters Health) - Gut flora from lean or obese humans induces similar phenotypes when transplanted into mice, providing more evidence that the intestinal microbiota plays a role in obesity, along with diet, researchers say.

The team of scientists also found that the microbiota from lean donors can invade and reduce weight gain in the obese-recipient mice if the mice are fed a healthy diet.

For their studies, the scientists recruited four human female twin pairs in which one twin was obese and the other lean. They transferred the intestinal microbiota in fecal samples from each of them into the intestines of germ-free mice.

Animals receiving a transplant from the obese twin donors developed increased adiposity but those receiving transplants from lean twin donors did not.

In essence, germ-free mice inoculated with microbiota from obese or lean human twins take on the microbiota characteristics of the donor, the scientists say. Those receiving the obese microbiota gained weight, while those receiving the lean microbiota remained lean.

"This wasn't attributable to differences in the amount of food they consumed, so there was something in the microbiota that was able to transmit this trait," Dr. Jeffrey Gordon, director of the Center for Genome Sciences and Systems Biology at Washington University School of Medicine in St. Louis, Missouri, who worked on the study, said in a statement.

Analysis of the bacterial communities showed that members of the Bacteroidetes phylum, particularly Bacteroides spp., could pass from the lean mice and colonize the obese mice, "suggesting that these bacteria were largely responsible for protection against increased adiposity," say the co-authors of a perspective piece accompanying the study online September 5 in Science.

However, it will be "important to verify in humans the activity of bacteria that are beneficial in mouse models," Dr. Alan Walker and Dr. Julian Parkhill from the Sanger Institute, Hinxton, United Kingdom write.

Dr. Gordon and colleagues also found that diet was an important factor in the transmission of microbiota and associated host phenotype. Lean gut microbes could infiltrate and displace obese gut microbes, preventing the mice from gaining weight, as long as they were on a healthy diet.

When the mice were fed a diet high in fiber and low in saturated fat, mice harboring the obese microbiota, when caged with mice harboring the lean microbiota, are invaded by the lean microbiota and do not develop increased adiposity, the scientists say. (Mice readily exchange their microbes by eating each other's feces when housed together.) By contrast, the obese microbiota does not effectively colonize mice harboring the lean microbiota, and these mice remain lean.

Walker and Parkhill say the fact that microbial protection from increased adiposity is only possible against the backdrop of a suitable host diet is "perhaps the most intriguing" observation the scientists made.

"It may be that future microbiota-based therapies for an obese individual will require an alteration in diet to aid colonization by beneficial microbes. This offers a potentially synergistic approach, whereby reduced caloric intake and increased fiber consumption not only have a positive impact on energy balance but might also promote transplanted microbial communities that are associated with leanness," they write.

It should also be noted that fecal transplants in humans have been used to beneficially alter the microbiota in a variety of ailments. "Notably, a recent study showed that fecal transplants from lean individuals into obese counterparts improved insulin sensitivity in some obese recipients. The procedure is not risk free, however, with the potential for introducing pathogens to the recipient," Walker and Parkhill say.

They think the mouse model presented by Dr. Gordon and colleagues "offers the potential to test human-derived bacterial strains, and accompanying dietary regimens, within a controlled mammalian host environment. The study is a step toward the ultimate goal of developing relatively simple mixtures of bacteria for testing as anti-obesity therapeutics," they conclude.

The authors were unavailable for comment by press time.

SOURCES: http://bit.ly/1dXTVgS and http://bit.ly/14pz6qu

Science 2013.