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Diabetes Care. 2018 Mar;41(3):398-405. doi: 10.2337/dc17-1967. Epub 2017 Dec 6.

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

Author information

1
Department of Internal Medicine 1, University of Kiel, Kiel, Germany.
2
Department of Food Technology, University of Kiel, Kiel, Germany.
3
Institute of Clinical Molecular Biology, University of Kiel, Kiel, Germany.
4
Institute for Experimental Cancer Research, University of Kiel, Kiel, Germany.
5
Institute of Medical Informatics and Statistics, University of Kiel, Kiel, Germany.
6
Zoological Institute, University of Kiel, Kiel, Germany.
7
Department of Biochemistry, University of Iowa, Iowa City, IA.
8
CONARIS Research Institute AG, Kiel, Germany.
9
Department of Internal Medicine 1, University of Kiel, Kiel, Germany matthias.laudes@uksh.de kschwarz-2@foodtech.uni-kiel.de s.schreiber@mucosa.de.
10
Department of Food Technology, University of Kiel, Kiel, Germany matthias.laudes@uksh.de kschwarz-2@foodtech.uni-kiel.de s.schreiber@mucosa.de.

Abstract

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.

PMID:
29212824
DOI:
10.2337/dc17-1967
[Indexed for MEDLINE]

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