GI Microbiome Modulator Shows Promise for Diabetes

A novel GI microbiome modulator improves oral glucose tolerance in patients with prediabetes and has the potential to improve treatment of patients with type 2 diabetes mellitus (DM), according to a pilot study.

“People living in wealthy cultures are inflicted with metabolic diseases, in part because of overeating processed food. Human physiology has limited ability to adapt to these modern dietary habits. In contrast, the ecosystem of the intestines, containing bacteria, fungi, and undigested and partially digested foods, quickly adapts. Shifts in the GI microbiome are documented for type 2 DM when compared to the microbiome of healthy individuals,” said lead author Mark Heiman, PhD, Chief Scientific Officer for MicroBiome Therapeutics, a biotechnology company that is developing the new drug.

The not-yet-named therapeutic, NM504, is the first in a new class of GI microbiome modulators. Recent scientific evidence suggests that microbial imbalance, or dysbiosis, in the gut contributes to the development of type 2 DM, Dr Heiman said.

NM504 is designed to shift the microbiota and their environment in specific ways to achieve improved health outcomes, Dr Heiman stated. The drug contains concentrated bioactive food ingredients, including inulin, beta-glucan, and polyphenolic antioxidant compounds.

Dr Heiman and colleagues conducted a 28-day, double-blind, randomized, placebo-controlled trial of 28 adults with prediabetes, 14 assigned to receive NM504 and 14 to receive placebo, to test whether NM504 improves oral glucose tolerance by modulating the GI microbiome. The drug was administered twice a day before breakfast or lunch and before dinner.

The microbiome modulator improved serum glucose levels during an oral glucose tolerance test at both 120 minutes and 180 minutes when compared with placebo. Insulin levels were similar between the 2 groups during the oral glucose tolerance testing. The improved glucose tolerance was associated with decreased circulating levels of alkaline phosphatase, C-reactive protein, and total cholesterol, Dr Heiman said.

Compared with placebo, the drug treatment also decreased the desire to eat. “A tendency for increased GLP-I levels and decreased octanoyl ghrelin levels in response to a meal tolerance test during week 3 was also observed,” Dr Heiman said. The patients tolerated NM504 well, with only a mild increase in flatulence, he noted.

“We think that NM504 attenuates absorption of glucose and bile salts. Other possible mechanisms of action in the lower gut include maintenance of the mucosal barrier, increased luminal exposure to antioxidants, and increased viscosity within the lumen,” said Dr Heiman. “Individual changes in microbiota abundance and short-chain fatty acid production were evident but were not different when grouped by treatment.”

In conclusion, Dr Heiman said, “NM504 is the first therapeutic to directly modulate the GI microbiome in prediabetics and in type 2 DM to improve oral glucose tolerance with decreased markers of inflammation and blood lipids.”

MicroBiome Therapeutics reports that it plans to develop NM504 or a closely related therapeutic as a prescription medicine to treat patients with prediabetes and those with DM.

Dr Heiman presented the results on June 23, 2014 at the 16th International Congress of Endocrinology and the Endocrine Society’s 96th Annual Meeting and Expo in Chicago.