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Obesity, GI Issues May Take Root in Gut Flora

By John Gever, Senior Editor, MedPage Today

Published: April 22, 2012

Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco.

Action Points

Manipulating the microbial flora within the intestine offers great promise for preventing or treating obesity and bowel disorders, but the precise means are not yet available.
Note that initial data for stool transplant are promising with very high response rates in patients with recurrent C. difficile infections.

NEW ORLEANS -- Manipulating the microbial flora within the intestine offers great promise for preventing or treating obesity and bowel disorders, but the precise means are not yet available, a researcher said here.

It's clear that the diverse communities of microorganisms living in the human gut are necessary to normal health, and that their derangement can lead to metabolic and gastrointestinal disorders, said Walter Coyle, MD, of the Scripps Clinic in La Jolla, Calif.

By the same token, then, it ought to be possible to alter the makeup of those communities, either to forestall development of such disorders or to treat them when they do occur, he told attendees at the American College of Physicians' annual meeting.

However, the science of the intestinal "microbiome" is still in its infancy and it remains unclear what changes to make, let alone how best to make them, Coyle said.

For starters, the mix of gut flora varies greatly between individuals. Coyle cited results of a study of three members of the same household, whose intestinal bacterial composition differed markedly.

Although environmental influences clearly help direct how an intestinal bacterial community will evolve, host factors probably also play a role. Despite the explosion in genetic research over the past 20 years, "host genetic influences [on the gut microbiome] remain unexplored," Coyle said.

One reason to suppose that host factors are important is that, after a person reaches adulthood, he or she usually has a characteristic "core" population of intestinal bacteria that remains stable even in the face of disruptions such as antibiotic treatment.

Coyle described a recent line of research in this area that may yield a new approach to obesity.

Two major categories of bacteria dominate in the intestine: Firmicutes and Bacteroidetes. Studies have found that obese people tend to have a higher ratio of the former to the latter.

One clinical study of 12 people eating a calorie-restricted diet for one year found that there was no weight loss until the ratio of Firmacutes to Bacteroidetes shifted.

Coyle said that it was compelling data, but cautioned that it didn't mean that simply killing the Firmacutes would lead to weight loss. It remains unknown whether metabolic changes drove the change in gut flora or the reverse, he said.

What is clear, however, is that certain microbial communities in the intestine are more efficient than others at harvesting energy from food and making it available to the human host.

He cited studies showing that gut microbes may contribute 100 to 200 calories daily to the human host.

A relatively inefficient community would be less able to contribute to weight gain and could even induce weight loss, Coyle suggested.

But consumers and the medical community are not waiting for a complete understanding of the gut microbiome and its relation to health and disease -- efforts to manipulate the microbiome are well underway, via probiotics, prebiotics, and fecal transplants.

Probiotics are now firmly entrenched and Coyle said he recommends them routinely to patients with irritable bowel disorders.

He noted that data from randomized, controlled trials are scant and difficult to interpret because of methodological variations. For irritable bowel syndrome, the best data point to a reduction in gurgling noises and bloating, with more mixed results in constipation and/or diarrhea endpoints.

Some studies with particular preparations have shown benefit against recurrent C. difficile diarrhea.

"The data are more and more compelling that we should probably be [giving probiotics] to all hospital patients," Coyle said, citing a 2007 study in which only five or six patients had to be treated to prevent one case of diarrhea.

Probiotics were shown to be helpful in ulcerative colitis in a trial, although only in patients who followed the study protocol rigorously. Many patients had no benefit, but there was "a dramatic effect" in others, Coyle said.

Also gaining popularity are prebiotics -- various types of fiber that act as fertilizer for certain types of intestinal microbes. Some breakfast cereals now boast them on their packages, although the frequent side effect of flatulence is not mentioned.

Coyle said the ideal obesity treatment, which has not yet appeared, could be a prebiotic that promotes a microbial mix with a lower "energy harvest" in the intestine.

Another more direct method for altering the gut microbiome is through fecal transplants. These are the only direct way to artificially boost anaerobic species, which make up about 99.9% of gut bacteria, according to Coyle.

At this point, most clinical studies have been case series involving diarrheal diseases. The initial data are promising, Coyle said, with very high response rates in patients with recurrent C. difficile infections.

To the extent that the gut microbiome helps drives obesity, fecal transplants could become a treatment approach.

Some early tests have been performed in animals, Coyles said. For example, germ-free but otherwise normal mice receiving stool from genetically fat mice showed greater weight gain compared with normal mice with wild-type flora.

That study did not test whether fat mice would lose weight after receiving stool from a thin animal, however, and whether artificially altering the gut microbiome in humans will lead to weight loss or gain remains speculative.

Coyle reported consulting or speaking fees from Takeda and CSA Medical, but declared that he had no financial relationships with companies selling probiotics or prebiotics.

Primary source: American College of Physicians
Source reference:
Coyle W "Our gut flora: the internist's guide" ACP 2012.

http://www.medpagetoday.com/MeetingCoverage/ACP/32295

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