Gut Flora May Be Tied to Obesity
By Nancy Walsh, Staff Writer, MedPage Today, Published: March 28, 2013
Reviewed by F. Perry Wilson, MD, MSCE; Instructor of Medicine, Perelman School of Medicine at the University of Pennsylvania and Dorothy Caputo, MA, BSN, RN, Nurse Planner
Individuals with detectable methane and hydrogen on breath testing had a higher body mass index (BMI) and greater percentage of body fat, suggesting a link between intestinal flora and obesity, researchers reported.
After adjustment for age, the mean BMI for individuals who had positive breath tests for both gases was 26.5 kg/m2, compared with BMIs of 24.1 kg/m2, 24.2 kg/m2, and 24 kg/m2, for those who had normal tests, were positive for hydrogen only, or were positive for methane only (P<0.02), respectively, according to Ruchi Mathur, MD, and colleagues from Cedars-Sinai Medical Center in Los Angeles.
In addition, total body fat in those positive for both methane and hydrogen was 34.1%, compared with 28.3% for those who were normal, 27.5% for those who tested positive for hydrogen, and 28% for those who were positive for methane (P?0.001), the researchers reported online in the Journal of Clinical Endocrinology and Metabolism.
A person whose exhaled breath contains large amounts of methane and hydrogen is likely to have gut colonization with Methanobrevibacter smithii, which scavenges hydrogen and, during its metabolism, releases methane.
"Obesity is a public health problem and is undoubtedly multifactorial. Dysregulations are seen in multiple areas of energy intake, expenditure, and storage. There is growing interest in the potential role of gut flora in the pathogenesis of obesity," the investigators observed.
The interaction between the methane and hydrogen molecules is thought to encourage greater production of short-chain fatty acids and increase nutrient availability, resulting in weight gain in the host, they explained.
"Our results may support this hypothesis, as the presence of both hydrogen and methane on breath test, but not either methane or hydrogen alone, is associated with higher BMI and percent body fat, perhaps because these subjects have an abundance of hydrogen to fuel methane production," they suggested.
Animal studies have shown that gut colonization with M. smithii is associated with weight gain and other metabolic changes, and these researchers previously found higher levels of exhaled methane in obese individuals.
To explore this possible association prospectively in a large population, Mathur's group invited 792 individuals referred for lactulose breath testing to participate.
The test involved the administration of 10 grams of lactulose syrup and 250 mL of water, after which breath samples were taken at regular intervals for 2 hours.
Levels of methane of at least 3 parts per million and hydrogen of 20 parts per million were considered positive.
A total of 28 individuals were positive for both methane and hydrogen. They more often were older and male, and reported more problems with constipation.
"Intestinal flora have been implicated in many mechanisms that may contribute to weight gain, including enhanced lipopolysaccharide production leading to insulin resistance, suppression of fasting-induced adipose factor, suppression of [AMP-activated protein kinase]-driven fatty acid oxidation in the liver, incretin regulation, and increased short-chain fatty acid production and absorption, thereby providing increased lipogenic substrates to the host," the researchers observed.
The finding that participants who were methane- and hydrogen-positive tended to experience constipation suggests that constipation may further increase the availability of nutrients, they noted.
In an animal model, the researchers previously showed a 60% slowing of intestinal transit time in the presence of methane. "We hypothesize that slowing of transit could result in greater time to harvest nutrients and absorb calories, representing another potential mechanism for weight gain," they wrote.
They called for further research to more fully elucidate the interplay of gut microbiota, metabolism, and obesity, and to establish causality.
"We're still in the process of finding out what's the chicken and what's the egg," said Ronald Tamler, MD, of the Mount Sinai Diabetes Center in New York, who was not involved in the study.
"Perhaps people who are obese just happen to have a different microbiome," he told MedPage Today.
Other limitations of the study included the absence of information about dietary patterns or differences in ethnicity, which could influence the interaction between the host and the gut microbiota.
In addition, the patients recruited into the study had been referred for lactulose breath testing because of abdominal symptoms, and may not be representative of the larger population.
The study was supported by the Beatrice and Samuel A. Seaver Foundation and the National Center for Advancing Translational Sciences.
The authors reported no disclosures.