Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study
Supplementation with Akkermansia muciniphila in overweight and obese human volunteers: a proof-of-concept exploratory study
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DOI：
10.1038/s41591-019-0495-2
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发表时间：
2019-07-01
期刊：
影响因子：
82.9
通讯作者：
Cani, Patrice D.
中科院分区：
文献类型：
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作者：
Depommier, Clara;Everard, Amandine;Cani, Patrice D.
代谢综合征的特征是一系列的共病，使个人易患心血管疾病和2型糖尿病的风险增加(1)。肠道微生物区系是肥胖相关疾病发病的一个新的关键因素(2)。在人类中，研究已经提供了证据表明，粘液阿克曼氏菌的丰度与超重、肥胖、未经治疗的2型糖尿病或高血压之间存在负相关(3-8)。由于粘液曲霉的给药从未在人类身上进行过研究，我们在超重/肥胖的胰岛素抵抗志愿者中进行了一项随机、双盲、安慰剂对照的先导研究；40人入选，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、循环血脂、内脏脂肪和体重)。次要结果是肠道屏障功能(即血浆脂多糖)和肠道微生物区系组成。在这项单中心研究中，我们证明了每天口服10(10)个活的或巴氏灭菌的粘液杆菌三个月是安全的，耐受性良好。与安慰剂相比，巴氏杀菌的粘液假单胞菌改善了胰岛素敏感性(+28.62+/-7.02%，P=0.002)，降低了胰岛素血症(-34.08+/-7.12%，P=0.006)和血浆总胆固醇(-8.68+/-2.38%，P=0.02)。与安慰剂组相比，补充巴氏杆菌的患者体重(-2.27+/-0.92公斤，P=0.091)、脂肪质量(-1.37+/-0.82公斤，P=0.092)和臀围(-2.63+/-1.14厘米，P=0.091)略有下降。在补充三个月后，粘液假单胞菌降低了肝功能障碍和炎症的相关血液标记物的水平，而整体肠道微生物群结构没有受到影响。综上所述，这项概念验证研究(临床试验编号：NCT02637115)表明，该干预是安全和耐受性良好的，补充粘液弧菌可以改善几个代谢参数。
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(1). The gut microbiota is a new key contributor involved in the onset of obesity-related disorders(2). In humans, studies have provided evidence for a negative correlation between Akkermansia muciniphila abundance and overweight, obesity, untreated type 2 diabetes mellitus or hypertension(3-8). 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 10(10) A. muciniphila bacteria either live or pasteurized for three months was safe and well tolerated. Compared to placebo, pasteurized A. muciniphila improved insulin sensitivity (+ 28.62 +/- 7.02%, P = 0.002), and reduced insulinemia (-34.08 +/- 7.12%, P = 0.006) and plasma total cholesterol (-8.68 +/- 2.38%, P = 0.02). Pasteurized A. muciniphila supplementation slightly decreased body weight (-2.27 +/- 0.92 kg, P = 0.091) compared to the placebo group, and fat mass (-1.37 +/- 0.82 kg, P = 0.092) and hip circumference (-2.63 +/- 1.14 cm, 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.