近日，比利时鲁汶药物研究所Patrice D. Cani及其团队进行了一项概念验证探索性研究，在超重和肥胖的人体志愿者中补充嗜粘蛋白阿卡曼氏菌。 2019年7月，国际知名学术期刊《自然—医学》发表了这一成果。

代谢综合征的特征是一系列的共病，这些共病使个体更易患心血管疾病和2型糖尿病。肠道微生物群是肥胖相关疾病发病的一个新的关键因素。在人类中，研究已经提供了证据，证明了嗜粘蛋白阿卡曼氏菌丰度与超重、肥胖、未经治疗的2型糖尿病或高血压之间存在负相关。由于从未在人类身上研究过嗜粘蛋白阿卡曼氏菌的使用，研究组对超重/肥胖的胰岛素抵抗志愿者进行了随机、双盲、安慰剂对照的试点研究;其中40人参与了试验，32人完成了试验。主要终点是安全性、耐受性和代谢参数(即胰岛素抵抗、循环脂质、内脏脂肪和体重)。其次是肠道屏障功能(即血浆脂多糖)和肠道微生物群组成。在这项单中心研究中，研究证明每天口服1010嗜粘蛋白阿卡曼氏菌的补充，无论是活的还是经过巴氏灭菌的，持续三个月是安全的，并且耐受性良好。与安慰剂相比，巴氏杀菌A. muciniphila改善胰岛素敏感性(+28.627.02%，P=0.002)，降低胰岛素血症(34.087.12%，P=0.006)和血浆总胆固醇(8.682.38%，P=0.02)。补充巴氏杀菌A. muciniphila与安慰剂组相比，体重(2.270.92kg, P=0.091)略有下降，与基线相比，脂肪量(1.370.82kg, P=0.092)和臀围(2.631.14cm, P=0.091)有所下降。经过三个月的补充，A. muciniphila降低了肝功能障碍和炎症相关血液标志物的水平，而整体肠道菌群结构不受影响。

综上所述，本研究为概念验证研究表明，干预是安全的，耐受性良好，补充嗜粘蛋白阿卡曼氏菌可改善几个代谢参数。

附：英文原文

Title: Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study

Author: Clara Depommier, Amandine Everard, Cline Druart, Hubert Plovier, Matthias Van Hul, Sara Vieira-Silva, Gwen Falony, Jeroen Raes, Dominique Maiter, Nathalie M. Delzenne, Marie de Barsy, Audrey Loumaye, Michel P. Hermans, Jean-Paul Thissen, Willem M. de Vos, Patrice D. Cani

Issue&Volume: Volume 25 Issue 7, July 2019

Abstract: Metabolic syndrome is characterized by a constellation of comorbidities that predispose individuals to an increased risk of developing cardiovascular pathologies as well as type 2 diabetes mellitus. The gut microbiota is a new key contributor involved in the onset of obesity-related disorders. In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension. Since the administration of A. muciniphila has never been investigated in humans, we conducted a randomized, double-blind, placebo-controlled pilot study in overweight/obese insulin-resistant volunteers; 40 were enrolled and 32 completed the trial. The primary end points were safety, tolerability and metabolic parameters (that is, insulin resistance, circulating lipids, visceral adiposity and body mass). Secondary outcomes were gut barrier function (that is, plasma lipopolysaccharides) and gut microbiota composition. In this single-center study, we demonstrated that daily oral supplementation of 1010 A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+28.627.02%, P=0.002), and reduced insulinemia (34.087.12%, P=0.006) and plasma total cholesterol (8.682.38%, P=0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (2.270.92kg, P=0.091) compared to the placebo group, and fat mass (1.370.82kg, P=0.092) and hip circumference (2.631.14cm, P=0.091) compared to baseline. After three months of supplementation, A. muciniphila reduced the levels of the relevant blood markers for liver dysfunction and inflammation while the overall gut microbiome structure was unaffected. In conclusion, this proof-of-concept study (clinical trial no. NCT02637115) shows that the intervention was safe and well tolerated and that supplementation with A. muciniphila improves several metabolic parameters.

DOI: 10.1038/s41591-019-0495-2

Source:https://www.nature.com/articles/s41591-019-0495-2