In Vivo evaluation of novel topical niacin nutriceuticals for improving gut microbiota and metabolic health

Fangmann, Daniela

Gut microbiota represent a potential novel target for future prediabetes and type 2 diabetes therapies. In that respect, niacin has been shown to beneficially affect the host-microbiome interaction in rodent models. RESEARCH DESIGN AND METHODS: We characterized more than 500 human subjects with different metabolic phenotypes regarding their niacin (nicotinic acid (NA) and nicotinamide (NAM)) status and their gut microbiome. In addition, NA and NAM delayed-release microcapsules were engineered and examined in vitro as well as in vivo in two human intervention studies (bioavailability study and proof-of-concept/safety study). RESULTS: We found a reduced α-diversity and Bacteroidetes abundance in the microbiome of obese human subjects associated with a low dietary niacin intake. Therefore, we developed delayed-release microcapsules targeting the ileo-colonic region to deliver increasing amounts of NA and NAM to the microbiome while preventing systemic resorption to avoid negative side effects (e. g. facial flushing). In vitro studies on these delayed-release microcapsules revealed stable conditions at pH 1.4, 4.5 and 6.8 followed by release of the compounds at pH 7.4, simulating the ileo-colonic region. In humans in vivo, gut-targeted delayed-release NA but not NAM produced a significant increase of the Bacteroidetes abundance. In the absence of systemic side effects, these favorable microbiome changes induced by microencapsulated delayed-release NA were associated with an improvement of biomarkers for systemic insulin sensitivity and metabolic inflammation. CONCLUSION: Targeted microbiome intervention by delayed-release NA might represent a future therapeutic option for prediabetes and type 2 diabetes.

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Fangmann, Daniela: In Vivo evaluation of novel topical niacin nutriceuticals for improving gut microbiota and metabolic health.

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