肠道微生物被认为是影响人类健康的主要因素。如今,文献中的绝大多数数据大多显示特定细菌与代谢参数之间的负相关或正相关。从这些观察来看,然后推断推定的有害或有益影响。Akkermansiamuciniphila是独特的例子之一,其与健康益处的相关性已在啮齿动物和人类的体内得到了因果关系的验证。在这项研究中,根据我们在超重/肥胖人群中获得的现有宏基因组数据和从两组个体(n=108)中获得的临床变量,我们确定了几种与粘虫A.通过分析qPCR和鸟枪宏基因组数据,我们发现,下颗粒的丰度与微生物丰富度和HDL-胆固醇水平呈正相关,与脂肪量呈负相关,脂肪细胞直径,胰岛素抵抗,瘦素水平,胰岛素,CRP,以及人类体内的IL6。因此,为了进一步探索这些强相关性是否可以转化为因果关系,我们研究了独特培养的亚下颗粒菌株(亚下颗粒DSM15176T)在肥胖和糖尿病小鼠中的作用,作为概念验证.引人注目的是,测量的肥胖和糖尿病的任何标志都没有显着差异(例如,体重增加,脂肪质量增加,葡萄糖耐量,肝脏重量,血浆脂质)在8周治疗结束时。因此,在用S.variabile补充后没有效果表明增加该细菌的肠道丰度没有转化为对小鼠的有益效果。总之,我们证明,尽管给定细菌与健康之间存在许多强相关性,概念验证实验需要进一步验证或不在体内。因此,因果关系研究的迫切需要从人类观察转向临床前验证.
Gut microbes are considered as major factors contributing to human health. Nowadays, the vast majority of the data available in the literature are mostly exhibiting negative or positive correlations between specific bacteria and metabolic parameters. From these observations, putative detrimental or beneficial effects are then inferred. Akkermansia muciniphila is one of the unique examples for which the correlations with health benefits have been causally validated in vivo in rodents and humans. In this study, based on available metagenomic data in overweight/obese population and clinical variables that we obtained from two cohorts of individuals (n = 108) we identified several metagenomic species (MGS) strongly associated with A. muciniphila with one standing out: Subdoligranulum. By analyzing both qPCR and shotgun metagenomic data, we discovered that the abundance of Subdoligranulum was correlated positively with microbial richness and HDL-cholesterol levels and negatively correlated with fat mass, adipocyte diameter, insulin resistance, levels of leptin, insulin, CRP, and IL6 in humans. Therefore, to further explore whether these strong correlations could be translated into causation, we investigated the effects of the unique cultivated strain of Subdoligranulum (Subdoligranulum variabile DSM 15176 T) in obese and diabetic mice as a proof-of-concept. Strikingly, there were no significant difference in any of the hallmarks of obesity and diabetes measured (e.g., body weight gain, fat mass gain, glucose tolerance, liver weight, plasma lipids) at the end of the 8 weeks of treatment. Therefore, the absence of effect following the supplementation with S. variabile indicates that increasing the intestinal abundance of this bacterium is not translated into beneficial effects in mice. In conclusion, we demonstrated that despite the fact that numerous strong correlations exist between a given bacteria and health, proof-of-concept experiments are required to be further validated or not in vivo. Hence, an urgent need for causality studies is warranted to move from human observations to preclinical validations.