Lara C. Pullen, PhD

June 24, 2014

CHICAGO — A new therapeutic is able to change the gut microbiome of patients with prediabetes and type 2 diabetes in just 4 weeks, and the changes corresponded with improved oral glucose tolerance as well as reduced cholesterol and decreased markers of inflammation.

Traditionally, microbiome research has focused on analyzing the types of bacteria in the stool, Mark Heiman, PhD, of MicroBiome Therapeutics in Indianapolis, Indiana, explained at ICE/ENDO 2014, where he presented his research. But he and his team took the investigation a step further, asking themselves, "What else can we measure in stool samples other than bacteria?...We are now measuring things like glucose and lactate and a lot of other things in the stool."

And it has become apparent there are distinct differences between the microbiome of individuals with prediabetes and type 2 diabetes when compared with the microbiome of healthy controls, he continued. For example, the diabetes-type microbiome produces less vitamin B12 and less vitamin K than that of healthy individuals. In addition, individuals with prediabetes and type 2 diabetes also have a decreased mucous barrier in the gut.

These observations led to the creation of NM504, a formulation of inulin, beta glucan, and anthocyanin-rich polyphenols. Inulin and beta glucan help in the production of short-chain fatty acids. Beta glucan also increases viscosity in the lumen, protects the mucous barrier of the gastrointestinal tract, and primes the gastrointestinal immune system.

NM504 appears to correct the microbiome shift seen in individuals with prediabetes and diabetes according to the results of the small, double-blind pilot study that Dr. Heiman reported.

"It's a very exciting, new area he is working on," explained Dr. Rakesh Sahay, consultant endocrinologist at Mediciti Hospital in India and comoderator of the session. "I think this is a very novel intervention that they looked at," he told Medscape Medical News.

Gordon Cutler, MD, of Deltaville, Virginia, a retired endocrinologist, was also enthusiastic: "This is a deliberate attempt to make a nutraceutical to change the microbiome."

Study Details

Dr. Heiman explained how, at the most basic level, he looks at a meal as a dose and considers most people with prediabetes and type 2 diabetes to be "overdosed." As a consequence, not all food becomes digested. The microbiome then uses the food as a substrate for growth. NM504 is designed to modulate the gastrointestinal microbiome without dietary modification.

In addition to growing and consuming excess calories, the microbiome also produces vitamins and signaling molecules, such as the short-chain fatty acid butyrate. Butyrate is the preferred substrate of colon cells and helps to maintain their health. The identification of these signaling molecules is an area of rapidly expanding research.

Dr. Heiman reported the results of his pilot study in 30 individuals, half of whom were randomized to NM504 twice a day prior to either breakfast or lunch and prior to dinner and the remainder to placebo, for 28 days. There were 14 individuals in each arm who completed the study. The microbiome modulator was well tolerated. In addition, patients receiving NM504 had improved serum glucose levels during a 120-minute and 180-minute glucose tolerance test compared with patients receiving placebo (P < .05).

Effect of NM504 Compared With Placebo

Outcome P
Improved glucose tolerance < 0.05
Decreased alkaline phosphatase 0.06
Decreased high-sensitivity C-reactive protein 0.012
Decreased total cholesterol 0.01
Decreased desire to eat 0.03
Increased stool IgA 0.03
Decreased pool pH 0.03

NM504 is the first therapeutic to directly modulate the GI microbiome in prediabetes and type 2 diabetes to improve oral glucose tolerance with decreased markers of inflammation and blood lipids, Dr. Heiman concluded.

Moreover, this improved metabolic state occurred without change in dietary habits, he noted, adding that follow-up studies will include more subjects and longer trials.

MicroBiome Therapeutics reports that the company plans to develop NM504 and/or a closely related therapeutic as a prescription medicine to treat prediabetes and diabetes. Dr. Sahay reported no relevant financial relationships. Dr. Cutler is retired from Eli Lilly.

Joint Meeting of the International Society of Endocrinology and the Endocrine Society: ICE/ENDO 2014; June 23, 2014. Abstract OR40-5.

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