Laboratory of Molecular Bacteriology, Department of Microbiology and Immunology, Rega Institute, KU Leuven, Leuven, Belgium.
Center for Microbiology, VIB, Leuven, Belgium.
Nature. 2020 May;581(7808):310-315. doi: 10.1038/s41586-020-2269-x. Epub 2020 May 6.
Microbiome community typing analyses have recently identified the Bacteroides2 (Bact2) enterotype, an intestinal microbiota configuration that is associated with systemic inflammation and has a high prevalence in loose stools in humans. Bact2 is characterized by a high proportion of Bacteroides, a low proportion of Faecalibacterium and low microbial cell densities, and its prevalence varies from 13% in a general population cohort to as high as 78% in patients with inflammatory bowel disease. Reported changes in stool consistency and inflammation status during the progression towards obesity and metabolic comorbidities led us to propose that these developments might similarly correlate with an increased prevalence of the potentially dysbiotic Bact2 enterotype. Here, by exploring obesity-associated microbiota alterations in the quantitative faecal metagenomes of the cross-sectional MetaCardis Body Mass Index Spectrum cohort (n = 888), we identify statin therapy as a key covariate of microbiome diversification. By focusing on a subcohort of participants that are not medicated with statins, we find that the prevalence of Bact2 correlates with body mass index, increasing from 3.90% in lean or overweight participants to 17.73% in obese participants. Systemic inflammation levels in Bact2-enterotyped individuals are higher than predicted on the basis of their obesity status, indicative of Bact2 as a dysbiotic microbiome constellation. We also observe that obesity-associated microbiota dysbiosis is negatively associated with statin treatment, resulting in a lower Bact2 prevalence of 5.88% in statin-medicated obese participants. This finding is validated in both the accompanying MetaCardis cardiovascular disease dataset (n = 282) and the independent Flemish Gut Flora Project population cohort (n = 2,345). The potential benefits of statins in this context will require further evaluation in a prospective clinical trial to ascertain whether the effect is reproducible in a randomized population and before considering their application as microbiota-modulating therapeutics.
微生物组群落分型分析最近确定了拟杆菌 2 型（Bact2）肠型，这是一种与全身炎症相关的肠道微生物群落结构，在人类稀便中高发。Bact2 的特征是拟杆菌比例高、粪杆菌比例低、微生物细胞密度低，其流行率在普通人群队列中为 13%，在炎症性肠病患者中高达 78%。报道的粪便一致性和炎症状态变化在向肥胖和代谢合并症进展过程中，我们提出这些变化可能同样与潜在的失调 Bact2 肠型的患病率增加相关。在这里，通过探索横断面 MetaCardis 体重指数谱队列（n=888）定量粪便宏基因组中的肥胖相关微生物组改变，我们确定他汀类药物治疗是微生物组多样化的关键协变量。通过关注不接受他汀类药物治疗的参与者亚组，我们发现 Bact2 的患病率与体重指数相关，从瘦或超重参与者的 3.90%增加到肥胖参与者的 17.73%。Bact2 型个体的全身炎症水平高于根据其肥胖状况预测的水平，表明 Bact2 是一种失调的微生物群落组合。我们还观察到，肥胖相关的微生物组失调与他汀类药物治疗呈负相关，导致接受他汀类药物治疗的肥胖参与者中 Bact2 的患病率降低至 5.88%。这一发现在伴随的 MetaCardis 心血管疾病数据集（n=282）和独立的 Flemish Gut Flora Project 人群队列（n=2345）中得到了验证。在这种情况下，他汀类药物的潜在益处需要在前瞻性临床试验中进一步评估，以确定其在随机人群中的效果是否可重复，并在考虑将其用作调节微生物组的治疗方法之前。
