Methane-Producing Microbes and Obesity
People with methane in their intestines caused by a particular kind of gut microbe are more likely to be obese, according to the findings of a study conducted at Cedars-Sinai. The findings were published in Journal of Clinical Endocrinology and Metabolism (JCEM) in April 2013. This discovery of gut microbes' role in obesity offers the Cedars-Sinai Diabetes and Obesity Research Institute (DORI) another path for scientists to explore, with the goal of developing novel treatments to reduce body mass index (BMI) and insulin resistance through detection and elimination of methane.
The study involved testing the breath of 792 human participants. Results divided participants into four groups, those with:
- Normal methane and hydrogen
- Hydrogen positive only
- Methane positive only
- Methane and hydrogen positive
Findings determined that methane- and hydrogen-positive participants generally had a significantly higher BMI than their counterparts. Researchers at Cedars-Sinai have shown that the predominant methane-producing microbe, or methanogen, in the human gastrointestinal tract (GI) is Methanobrevibacter smithii (M. smithii). This microbe is thought to work in conjunction with hydrogen-producing bacteria to facilitate increased energy harvest for the human host. Methane-positive patients generally experience higher occurrences of constipation-predominant irritable bowel syndrome (IBS). Previous studies have shown that methane gas slows intestinal transit and methanogens affect caloric harvest.
Ruchi Mathur, MD, FRCPC, director of the Diabetes Outpatient Treatment and Education Center and an endocrinologist with the Center for Weight Loss, has been looking at gut microbes for possible solutions to treating obesity and Type 2 diabetes. Mathur's studies using human participants as well as research in the laboratory of Mark Pimentel, MD, have targeted M. smithii.
Mathur has also received funding from The American Diabetes Association to perform the following clinical trial at Cedars-Sinai:
- Eradicating methane-producing organisms in prediabetic and obese individuals to change outcomes
- Examine stools, gastric transit times and breath for methane and glucose tolerance.
- Supply 10-day course of antibiotics along with isocaloric diet.
- Repeat collection of stools, gastric transit times, breath and glucose tolerance after course of treatment, to compare.
- Determine whether treatment changes outcomes in insulin and glucose metabolism and other parameters, such as lipid levels.
- Examine stools, gastric transit times and breath for methane and glucose tolerance.
Understanding the roles of microbes and gases in the gut and how these affect weight gain and glycemic control may provide new approaches for curbing the obesity epidemic and Type 2 diabetes. Collaborative studies are being planned with DORI and Mathur's team to further explore the role of gut microbes on human metabolism.
- Mathur R, Kim G, Morales W, Sung J, Rooks E, Pokkunuri V, Weitsman S, Barlow GM, Chang C, Pimental M. Intestinal Methanobrevibacter smithii but not total bacteria is related to diet-induced weight gain in rats. Obesity (Silver Spring). 2013 Apr;21(4):748-754. http://onlinelibrary.wiley.com/doi/10.1002/oby.20277/abstract.
- Mathur R, Amichai M, Chua KS, Mirocha J, Barlow GM, Pimentel M. Methane and hydrogen positivity on breath test is associated with greater body mass index and body fat. J Clin Endocriol Metab. 2013 Apr;98(4):E698-702. http://press.endocrine.org/doi/full/10.1210/jc.2012-3144?queryID=13%2F133050.
- Basseri RJ, Basseri B, Pimentel M, Chong K, Youdim A, Low K, Hwang L, Soffer E, Chang C, Mathur R. Intestinal methane production in obese individuals is associated with a higher body mass index. Gastroenterol Hepatol (NY). 2012 Jan;8(1):22-28. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3277195/.
- Szczepaniak LS, Victor RG, Mathur R, Nelson MD, Szczepaniak EW, Tyer N, Chen I, Unger RH, Bergman RN, Lingvay I. Pancreatic steatosis and its relationship to ß-cell dysfunction in humans: racial and ethnic variations. Diabetes Care. 2012 Nov;35(11):2377-2383. http://care.diabetesjournals.org/content/35/11/2377.full.
- Pimentel M, Mathur R, Chang C. Gas and the microbiome. Curr Gastroenterol Rep. 2013 Dec;15(12):356. http://link.springer.com/article/10.1007/s11894-013-0356-y.
- Ezeh U, Pall M, Mathur R, Dey D, Berman D, Chen IY, Dumesic DA, Azziz R. Effects of endogenous androgens and abdominal fat distribution on the interrelationship between insulin and non-insulin-mediated glucose uptake in females. J Clin Endocrinol Metab. 2013 Apr;98(4):1541-1548. http://press.endocrine.org/doi/full/10.1210/jc.2012-2937.
- Mathur R, Goyal D, Kim G, Barlow GM, Chua KS, Pimentel M. Methane-producing human subjects have higher serum glucose levels during oral glucose challenge than non methane producers: a pilot study of enteric methanogens on glycemic regulation. Res J Endocrinol and Metab. 2014;2:2:ISSN 2053-3640. http://www.hoajonline.com/endocrinolmetab/2053-3640/2/2.
- Lin E, Barlow GM, Mathur R. The microbiome in non-alcoholic fatty liver disease: associations and implications. Ann Gastroenterol. 2014;27(2):181-183. http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3982640/.
- Lingvay I, Mathur R, Szczpaniak E, Szczpaniak L. Ethnic diversity in beta-cell function susceptibility to pancreatic triglyceride levels: pilot investigation. J Diabetes Metab. 2014;5:348. http://omicsonline.org/open-access/ethnic-diversity-in-betacell-function-susceptibility-to-pancreatic-triglyceride-levels-pilot-investigation-2155-6156.1000348.php?aid=27190.
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