OR40-5 Improved Oral Glucose Tolerance in Prediabetics and Type 2 Diabetics (T2D) in a Pilot Clinical Trial Testing a Novel Gastrointestinal (GI) Microbiome Modulator

Program: Abstracts - Orals, Poster Preview Presentations, and Posters
Session: OR40-Type 2 Diabetes: Beta Cell Function and Novel Interventions
Clinical/Translational
Monday, June 23, 2014: 11:30 AM-1:00 PM
Presentation Start Time: 12:30 PM
W185 (McCormick Place West Building)

Poster Board MON-0957
Mark Louis Heiman, PHD1, Jeffrey H Burton2, Elena Deych3, William D Shannon4 and Frank Lyons Greenway III, MD5
1MicroBiome Therapeutics, Indianapolis, IN, 2Pennington Biomedical Research Center, Baton Rouge, LA, 3Washington Univ, St. Louis, St. Louis, MO, 4BioRankings, LLC, St. Louis, MO, 5Pennington Biomed Res Ctr, Baton Rouge, LA
People living in wealthy cultures are inflicted with metabolic diseases, in part, because of over eating processed food.  Human physiology has limited ability to adapt to these modern dietary habits. In contrast, the ecosystem of the intestines; containing bacteria, fungi, undigested- and partially digested- foods, quickly adapts.  For example, shifts in the GI microbiome are documented for T2D when compared to the microbiome of healthy individuals (1,2).  The first microbiome modulator designed to treat dysbiosis in T2D is NM504.  A trial was done to test if NM504 improves the oral glucose tolerance of prediabetics and untreated T2D by modulating the GI microbiome.  Thirty subjects were enrolled in the double-blind, randomized, placebo-controlled trial for 28 days (14 subjects completed each arm).  NM504 was administered twice a day prior to either breakfast or lunch and prior to dinner.  The microbiome modulator was well tolerated and improved (p < 0.05, n=14) the serum glucose levels during an oral glucose tolerance test at both 120 - and 180 - min when compared to those values in subjects assigned to the placebo (n=14).  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 ALK phosphatase (p=0.06, n=14), hsCRP (p=0.012, n=14), and total cholesterol (p=0.01, n=14).  NM504 treatment also decreased the desire to eat (p=0.03, n=14), increased stool IgA levels (p=0.03, n=14), and decreased stool pH (p=0.03, n=14). 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, increased viscosity within the lumen.  Individual changes in microbiota abundance and short chain fatty acid production were evident but were not different when grouped by treatment.  A tendency for increased GLP-I levels and decreased ocatanoyl ghrelin levels in response to a meal tolerance test during week 3 was also observed.  In conclusion, NM504 is the first therapeutic to directly modulate the GI microbiome in prediabetics and in T2D to improve oral glucose tolerance with decreased markers of inflammation and blood lipids.  Moreover, this improved metabolic state occurred without change in dietary habits. Follow-up studies will include more subjects and longer trials.

(1) Qin et al., Nature 2012; 490: 55.  (2) Karlsson et al., Nature 2013; 498: 99

Disclosure: MLH: Chief Scientific Officer, MicroBiome Therapeutics, Chief Scientific Officer, MicroBiome Terapeutics, Chief Scientific Officer, MicroBiome Therapeutics. ED: Collaborator, BioRankings. WDS: Chief Scientific Officer, BioRankings. FLG III: Advisory Group Member, MicroBiome Therapeutics. Nothing to Disclose: JHB

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