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.

中文翻译：

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微囊化的缓释烟酸靶向微生物干预有益地影响人类的胰岛素敏感性。

目的肠道菌群代表了未来糖尿病前期和2型糖尿病治疗的潜在新靶标。在这方面，烟酸已被证明可以有效地影响啮齿动物模型中宿主-微生物组的相互作用。研究设计与方法我们对500多个具有不同代谢表型的人类受试者的烟酸（烟酸[NA]和烟酰胺[NAM]）状态及其肠道微生物组进行了表征。此外，在两项人类干预研究（生物利用度研究和概念验证/安全性研究）中，对NA和NAM缓释微胶囊进行了工程设计并在体外和体内进行了检查。结果我们发现与饮食中烟酸摄入量低有关的肥胖人类受试者的微生物组中的α多样性和拟杆菌含量降低。因此，我们开发了针对回肠结肠区域的延迟释放微胶囊，以向微生物组中递送越来越多的NA和NAM，同时防止系统吸收，避免了不良副作用（例如面部潮红）。对这些缓释微胶囊的体外研究表明，在pH 1.4、4.5和6.8时条件稳定，随后在pH 7.4释放化合物，模拟了回肠结肠区域。在体内的人体中，肠道靶向的延迟释放NA（而非NAM）使拟杆菌的丰度显着增加。在没有全身性副作用的情况下，微囊化缓释NA诱导的这些有利的微生物组变化与全身性胰岛素敏感性和代谢性炎症的生物标志物的改善有关。