The gut microbiome, a collection of microbes living in the gastrointestinal tract, has emerged as an attractive target for pharmaceutical intervention for the treatment of a variety of disorders. This is the fourth article in a series on advancements in microbiome research and development. This installment will focus on the connections between the gut microbiome and obesity. Upcoming articles will continue to review important topics in this technology area, and patents of interest.
By Jessica Miles* and Anthony D. Sabatelli** --
Some of the earliest evidence for the relationship between the microbiome and obesity came from studies of antibiotics and their association with weight gain in livestock, which pointed to a link between microbiome composition and weight maintenance. A 2006 study from the laboratory of the prominent researcher Jeffrey Gordon uncovered a mechanism by which some gut bacteria trigger obesity. Lead author Peter Turnbaugh and his colleagues noted that obese mice had different microbiomes than their lean littermates. The same was true of lean and obese human twins. When Gordon's team characterized this phenomenon, they found that the microbiomes in obese mice and humans obtain more calories from food as compared to the microbiomes of their lean counterparts. In addition, when the researchers transferred the gut bacteria of an obese mouse to a germ free one, the formerly germ free mouse became obese.
A follow-up study in 2009 further characterized differences in the microbiomes of lean and obese twins, highlighting a shift in relative abundance of and a decrease in the number of different microbiome members that are associated with the onset of obesity. Turnbaugh, his colleagues, and other prominent leaders in this subject area are highlighted in Table 1.
Dysbiosis of the microbiome is now a hallmark of obesity and the basis for microbiome-based treatments. Gut bacteria are a particularly attractive therapeutic target because of the paucity of safe and effective treatments for obesity. Current treatments for obesity, such as lorcaserin (Belviq) have been associated with cancer and heart valve dysfunction. Previous medications, such as fenfluramine (a component of Fen-Phen) were taken off the market due to concerns about heart-related side effects.
Several microbiome companies are working to address this unmet need for obesity therapies, and some treatments are also used for related metabolic disorders, such as diabetes and cardiovascular disease. MicroBiome Therapeutics LLC has three candidate microbiome modulators in its pipeline: One candidate, MT303 contains a small molecule glyceollin microbiome modulator, intended to increase bacterial diversity in the gut and reduce fat absorption. Another, NM505, is being evaluated in clinical trials for the treatment of diabetes. Second Genome has identified metabolic disease as a "focus" area: in 2014, the company announced a partnership with Pfizer and plans to launch a study on obesity and metabolic disease, and began a collaboration with the Mayo Clinic. A Swedish company, Metabogen, is developing a platform for identifying biomarkers of atherosclerosis and diabetes. Seres Therapeutics, which boasted a $134 million IPO last June, is evaluating whether their Ecobiotic® drugs, currently used for the treatment inflammatory bowel syndrome, are effective against metabolic diseases, including type II diabetes.
Manipulating the microbiome may hold the key to treating obesity, diabetes, and cardiovascular disease. Due to a combination of continued research, the efforts of several prominent microbiomics companies, and an unmet need for safe, effective obesity therapies, prospects for the field remain high. Stay tuned for the next installment of this series, a follow up to this article that which will review microbiomics patents relating to obesity and metabolic disorders.
For additional information regarding this topic, please see:
• "Guest Post -- The Emergent Microbiome: A Revolution for the Life Sciences – Part III, Psychobiotics," October 13, 2015
• "Guest Post -- The Emergent Microbiome: A Revolution for the Life Sciences – Part II, 2015 Patent Trends," August 11, 2015
• "Guest Post -- The Emergent Microbiome: A Revolution for the Life Sciences – Part I, R&D Leaders," August 10, 2015