Wednesday, January 21, 2009

Gut Microbes Shift with Obesity, Upended by Gastric Bypass

Gut Microbes Shift with Obesity, Upended by Gastric Bypass

NEW YORK (GenomeWeb News) – The microbes living in our guts are linked — and could potentially contribute — to our weight. And these microbial communities are overhauled following gastric bypass surgery-assisted weight loss, according to a new study scheduled to appear online this week in the Proceedings of the National Academy of Sciences.

Using a combination of Sanger and Roche 454 sequencing technology, a team of researchers from Arizona State University, Arizona's Mayo Clinic, and the University of Arizona assessed the gut microbes of nine individuals who were either normal weight, obese, or had lost weight following Roux-en-Y gastric bypass surgery.

The team found that gastric bypass surgery was linked to a dramatic shift in individuals' gut microbes. They also detected an intriguing pattern in the microbial community within obese subjects: these individuals harbored a combination of hydrogen-producing and -consuming microbes that researchers say may ramp up the amount of energy harvested from their food.

By understanding such shifts, the team hopes to come up with new obesity treatments as well as markers to predict who is at risk of becoming obese.

Roughly four million Americans are affected by obesity and about 300,000 die from obesity-related conditions annually. Although increased food energy intake and a lack of physical activity are partly to blame, the authors noted, systems governing the body's energy balance could also be a factor.

Roux-en-Y and other bariatric surgeries are the most effective obesity treatments available to date. By bypassing part of the stomach and small intestine, the surgery limits the amount and type of food an individual can eat.

Such procedures are associated with a certain degree of nutrient malabsorption, changes in stomach acid exposure, and other gastrointestinal changes that could potentially alter the gut microbial community.

In an effort to understand these changes, the researchers used a combination of Sanger and Roche 454 sequencing to amplify and sequence microbial 16S sequences from stool samples taken from nine adults: three who were normal weight, three who were classified as morbidly obese, and three who had undergone gastric bypass surgery between eight and 15 months prior to the study.

Using massively parallel sequencing on the V6 hypervariable region of the 16S rRNA gene, the team generated 184,094 high-quality reads — an average of 20,455 reads per individual tested. These reads represented sequence from between 419 and 575 phylotypes.

Despite the diverse microbial communities and inter-personal differences within each trio of individuals, the researchers found groups of microbes that clustered together depending on weight or bypass surgery.

Whereas Firmicutes were the most common type of bacteria in normal weight and morbidly obese individuals, Gammaproteobacteria were dominant in the guts of those who'd had gastric bypass. These individuals also had more Enterobacteriaceae and Fusobacteriaceae and fewer bacteria from the order Clostridia.

"The large bacterial population shift seen in the post-gastric-bypass individuals may reflect the double impact of the gut alteration caused by the surgical procedure and the consequent changes in food ingestion and digestion," the authors wrote.

Because patients who've had gastric bypass surgery have a shorter gastrointestinal tract, lead author Husen Zhang, a post-doctoral researcher at ASU's Biodesign Institute, told GenomeWeb Daily News, they also have a higher concentration of oxygen in their gut. Not surprisingly then, he said the team found more facultative anaerobes — microbes that are capable of using oxygen — in that the guts of those who'd had the surgery.

Still, the researchers cautioned, more research is needed to determine the implications of this new microbial consortium. "The drastic change may or may not reflect a deficiency in beneficial microbes," Zhang said. "Maybe these patients need some kind of supplement."

The team also detected differences in the microbes found in the guts of the morbidly obese. While individuals from the normal weight and gastric bypass groups carried hordes of bacteria from the Verrucomicrobia phylum, for example, obese individuals did not. Instead, obese individuals often carried bacteria from the Prevotellaceae, a type of Bacteroidetes.

Both sequencing and quantitative real-time PCR indicated that the three obese subjects tested also carried microbes that produce or use hydrogen — including hydrogen-producing bacteria from the Prevotellaceae family and hydrogen-consuming Archaea.

Based on these results, the researchers speculated that there is teamwork taking place between the bacteria and archaea living in the guts of the obese. And, Zhang said, he and his team suspect that this cooperation may increase the amount of energy that obese individuals extract from food.

The researchers don't know yet whether this microbial community causes — or is a consequence of — obesity, senior author Rosa Krajmalnik-Brown, a researcher at ASU's Biodesign Institute, told GenomeWeb. But if the team can verify that gut microbes contribute to weight problems, she said, it may be possible to develop new microbe-based obesity treatments.

And although physicians and researchers don't need a marker for morbid obesity itself, Krajmalnik-Brown added, the archaeal-bacterial community associated with obesity may eventually help to distinguish individuals who are at increased risk of becoming obese.

Next, the team plans to do similar studies in larger groups of individuals over time, to determine, for example, how gut microbes vary during weight-loss programs or before and after bypass surgery.

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