Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans | Zendy

Daniela Fangmann | Zendy; Eva-Maria Theismann | Zendy; Kathrin Türk | Zendy; Dominik M. Schulte | Zendy; I Relling | Zendy; Katharina Hartmann | Zendy; Julia K. Keppler | Zendy; J Knipp | Zendy; Ateequr Rehman | Zendy; FemkeAnouska Heinsen | Zendy; André Franke | Zendy; Lennart Lenk | Zendy; Sandra FreitagWolf | Zendy; Esther Appel | Zendy; Stanislav N. Gorb | Zendy; Charles Brenner | Zendy; Dirk Seegert | Zendy; Georg H. Waetzig | Zendy; Philip Rosenstiel | Zendy; Stefan Schreiber | Zendy; Karin Schwarz | Zendy; Matthias Laudes | Zendy

Open Access

Targeted Microbiome Intervention by Microencapsulated Delayed-Release Niacin Beneficially Affects Insulin Sensitivity in Humans

Author(s) -

Daniela Fangmann,

Eva-Maria Theismann,

Kathrin Türk,

Dominik M. Schulte,

I Relling,

Katharina Hartmann,

Julia K. Keppler,

J Knipp,

Ateequr Rehman,

FemkeAnouska Heinsen,

André Franke,

Lennart Lenk,

Sandra FreitagWolf,

Esther Appel,

Stanislav N. Gorb,

Charles Brenner,

Dirk Seegert,

Georg H. Waetzig,

Philip Rosenstiel,

Stefan Schreiber,

Karin Schwarz,

Matthias Laudes

Publication year - 2017

Publication title -

diabetes care

Language(s) - English

Resource type - Journals

SCImago Journal Rank - 6.636

H-Index - 363

eISSN - 1935-5548

pISSN - 0149-5992

DOI - 10.2337/dc17-1967

Subject(s) - microbiome , niacin , medicine , prediabetes , type 2 diabetes , nicotinamide , diabetes mellitus , bioavailability , dysbiosis , insulin resistance , gut flora , pharmacology , endocrinology , immunology , bioinformatics , biology , biochemistry , enzyme

OBJECTIVE 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 and 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. We therefore developed delayed-release microcapsules targeting the ileocolonic 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 ileocolonic region. In humans in vivo, gut-targeted delayed-release NA but not NAM produced a significant increase in the abundance of Bacteroidetes. 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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