This study is the first to demonstrate a significant association between the presence of methane on breath testing and the degree of obesity. In a bivariate analysis, methanepositive obese subjects had a BMI that was 6.7 kg/m2higher than the BMI of methane-negative obese subjects. In multivariate analysis, methane status remained significant after controlling for constipation and other variables.
Obesity is a growing epidemic in the United States; currently, 1 in 3 Americans over the age of 20 years are obese, and 2 in 3 Americans are overweight.23
The healthcare burden of obesity is extremely high, as obesity is associated with type 2 diabetes mellitus, coronary artery disease, hypertension, cerebral vascular accidents, numerous malignancies, and other diseases that lead to considerable morbidity and mortality.25
The economic cost of these comorbidities is threatening an already inundated healthcare system.1
During the past 3 decades, caloric consumption has significantly increased in concert with a considerable reduction in physical activity, which together have contributed greatly to the high prevalence of obesity.27
The human gut is an intricate microbial ecosystem populated by approximately 1014
bacteria, alterations to which may contribute to obesity through increasing dietary energy harvest and adipose deposition.28
Researchers' understanding of the microbial composition of the gut is improving as newer technologies enable better identification and classification of enteric flora.29
For example, the metagenome of the gut microbiome has recently been cataloged.32
An individual's indigenous gut flora is established within the first year of life and is progressively modified throughout adulthood by endogenous and exogenous factors, including dietary intake and genetic predisposition.33
While obesity generally results from an imbalance between energy consumption (eating) and energy expenditure (physical activity and catabolism), an increase in the efficiency with which an individual's gut flora can extract energy from food may also contribute to obesity.39
Bäckhed and colleagues showed that germ-free mice weighed significantly less than mice with normal gut flora, illustrating the significant role of gut microbiota in nutrient metabolism.40
Further, colonization of the distal gut of germ-free mice with flora from their conventionally raised, obese counterparts resulted in excessive weight gain. Germ-free lean mice colonized with the microbiome of obese mice experienced significant increases in body fat compared to mice colonized with a conventional micro biome.14
These data demonstrate that gut flora can play a significant role in the development of obesity.
In humans, methane-producing archaea (methano-gens) produce methane through anaerobic fermentation; the most common methanogen in the human gut is M. smithii
, which is found in 70% of human subjects.30
Analysis of expiratory methane by lactulose breath testing can serve as an indirect measure of methane produc-tion.17
A minority of subjects (15%) produce large quantities of methane early in the breath test, suggesting a greater methane potential, and increased methane production as measured by breath testing correlates with increased levels of M. smithii
in stool, as determined by quantitative polymerase chain reaction assay.13
Methanogens remove hydrogen atoms and accelerate the fermentation of polysaccharides and carbohydrates, thus increasing the production of short-chain fatty acids that are subsequently absorbed in the intestines and serve as an additional source of energy for the human host.45
This more efficient energy extraction may lead to weight gain and may ultimately contribute to obesity.46
A study by Zhang and colleagues that utilized a different modality for methane measurement (stool assays) also demonstrated a promising association between methane and obesity in human subjects.47
Besides alterations in luminal metabolic processing, methane gas itself may influence motility. Recently, our group demonstrated that infusion of methane gas into the small intestine resulted in a slowing of small intestinal transit by 59% in an in vivo animal model.15
The slowing effects of methane on intestinal transit could have 2 possible consequences: First, slowing of intestinal transit could increase the duration of nutrient absorption in the postprandial state. Second, slowing of transit could result in higher levels of gut microflora. Both of these effects could lead to increased weight gain and the development of obesity.
The current study demonstrates that humans with methane detectable via breath testing have a significantly higher BMI than methane-negative controls. This finding was remarkable because all subjects in this study were obese, per the study's inclusion criteria. This result remained significant when controlling for other factors, including constipation, which is an indicator of slowed transit. This result may be due to the collinearity of constipation and BMI. Although it remains unclear why methane was significant even when controlling for the clinical manifestation of transit (ie, constipation), the results of a recent animal study may help to explain this observation. In a study that has been submitted for publication, our group found for the first time that colonization of the rat gut with the methanogen M. smithii is not limited to the large bowel but rather extends to the small bowel, including the ileum, jejunum, and duodenum. Therefore, obese human subjects may have increased numbers of methanogens in the small bowel, rather than in the colon, thus exerting slowing effects in the small bowel while preserving colonic transit.
Another interesting finding in this study was that subjects who were currently taking antidepressant medications had a BMI that was 3.91 kg/m2 lower than the BMI of subjects who were not taking antidepressants. While specific antidepressant medications have been shown to produce weight gain, obesity is also associated with depression, and overeating can be a sign of depression. Thus, one possible explanation for the observed data is that depression leads to a sedentary lifestyle and self-destructive behaviors such as overeating in some subjects. By treating depression with antidepressant medications, perhaps the provocation for these eating behaviors is decreased and the desire to exercise or engage in other physical activities is increased. In addition, tricyclic antidepressants have anticholiergic side effects; these medications can, therefore, lead to suppression of appetite due to delayed gastric emptying. Further studies with larger numbers of subjects would be required to test this association.
This study clearly demonstrates a relationship between intestinal methane production and BMI. However, there are some limitations to the study's data. First, this is a preliminary study that was intended to evaluate a novel relationship; thus, the sample size was relatively small, and the study was performed at a single center. The observed lack of statistical significance for some comparisons may therefore be related to the small sample size in the methane-positive group, although the multivariate analysis found that methane remained an independent predictor of elevated BMI when controlling for antidepressant use (P
<.001) and when controlling for both constipation and antidepressant use (6.55 kg/m2
greater BMI; P
=.003). Second, the subjects in this study were all seeking assistance for surgical or medical weight loss, and such patients may be different from obese individuals who are not actively trying to lose weight. Therefore, larger studies will be needed to confirm our findings. However, our data are supported by recent findings in gnotobiotic animal studies; Samuel and coauthors found that Bacteroides thetaiotaomicron— M. smithii
co-colonization produced a significant increase in host adiposity compared to monoassociated animals or B. thetaiotaomicron—Desulfovibrio piger
As M. smithii
is the most common methanogen colonizing the human gut, the increased breath methane concentration associated with greater BMI in this study also likely results from increased M. smithii
In conclusion, this study demonstrates that the presence of methane is associated with higher BMI among obese subjects. This finding further supports the role of gut flora in obesity. Moreover, this information may expand on the evolving data in animal models, which support a specific association between methanogenic archaea and obesity. While the mechanism of this association remains unknown (slowed transit vs metabolic interactions of gut microflora), these intriguing results lay the foundation for further research in this area.