A consortium of seven commensal bacteria promotes gut microbiota recovery and strengthens ecological barrier against vancomycin-resistant enterococci.

IF 13.8 1区 生物学 Q1 MICROBIOLOGY
Alan Jan, Perrine Bayle, Nacer Mohellibi, Clara Lemoine, Frédéric Pepke, Fabienne Béguet-Crespel, Isabelle Jouanin, Marie Tremblay-Franco, Béatrice Laroche, Pascale Serror, Lionel Rigottier-Gois
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Abstract

Background: Vancomycin-resistant enterococci (VRE) often originate from the gastrointestinal tract, where their proliferation precedes dissemination into the bloodstream, and can lead to systemic infection. Uncovering the actors and mechanisms reducing the intestinal colonisation by VRE is essential to control infection. We aimed to identify commensal bacteria that interfere with VRE gut colonisation or act as an ecological barrier.

Results: We performed a 3-week longitudinal analysis of the gut microbiota composition and VRE carriage levels during microbiota recovery in mice colonised with VRE after antibiotic-induced dysbiosis. By combining biological data and mathematical modelling, we identified 15 molecular species (OTUs) that negatively correlated with VRE overgrowth. Six strains representative of these OTUs were collected, cultivated and used in mixture with a seventh strain (Mix7) in two different mouse lines challenged with VRE. Of the seven strains, three belonged to Lachnospiraceae, one to Muribaculaceae, one to Ruminococcaceae and two to Lactobacillaceae. We found that Mix7 led to a better recovery of the gut microbiota composition and reduced VRE carriage. Differences in the effect of Mix7 were observed between responder and non-responder mice. These differences were associated with variations in the composition of the initial microbiota and during recovery and represent potential biomarkers for predicting response to Mix7. In a mouse model of alternative stable state of dysbiosis, response to Mix7 was associated with higher concentrations of short-chain fatty acids (acetate, propionate, butyrate) and a range of metabolites including bile acids, reflecting the recovery of the microbiota back to initial state. Furthermore, Muribaculum intestinale strain was required to obtain the Mix7 effect on VRE reduction in vivo, but the presence of at least one of the other six strains was needed. None of the supernatant of the seven strains, alone or in combination, inhibited VRE growth in vitro. Interestingly, five strains belong to species shared among humans and mice, and the other two have human functional equivalents.

Conclusions: An innovative approach based on mathematical modelling of the microbiota composition permitted to identify a mixture of commensal bacterial strains, which improves the ecological barrier effect against VRE. The mechanisms are dependent on the recovery and initial composition of the microbiota. Ultimately, this work will enable a move towards a personalised medicine by targeting predisposed patients presenting a risk of infection, such as neutropenic or bone-marrow transplant patients, and likely to respond to supplementation with commensal strains, providing new live biotherapeutic products and biomarkers to predict response to supplementation. Video Abstract.

一个由7种共生细菌组成的联合体促进肠道菌群的恢复,并加强对万古霉素耐药肠球菌的生态屏障。
背景:万古霉素耐药肠球菌(VRE)通常起源于胃肠道,其增殖先于传播进入血液,并可导致全身感染。揭示VRE减少肠道定植的作用因素和机制对控制感染至关重要。我们的目的是鉴定干扰VRE肠道定植或作为生态屏障的共生细菌。结果:我们对抗生素诱导的生态失调后VRE定植的小鼠在微生物群恢复期间的肠道微生物群组成和VRE携带水平进行了为期3周的纵向分析。通过结合生物学数据和数学模型,我们确定了15个与VRE过度生长负相关的分子物种(OTUs)。收集具有代表性的6株OTUs,与第7株(Mix7)混合培养,在两个不同的VRE攻毒小鼠品系中使用。7株菌株中,3株属于毛螺科,1株属于Muribaculaceae, 1株属于Ruminococcaceae, 2株属于乳酸杆菌科。我们发现Mix7可以更好地恢复肠道菌群组成并减少VRE携带。在有反应小鼠和无反应小鼠之间观察Mix7的作用差异。这些差异与初始微生物群组成和恢复期间的变化有关,并代表了预测对Mix7反应的潜在生物标志物。在生态失调稳定状态的小鼠模型中,对Mix7的反应与较高浓度的短链脂肪酸(醋酸酯、丙酸酯、丁酸酯)和一系列代谢物(包括胆汁酸)相关,反映了微生物群恢复到初始状态。此外,要获得Mix7在体内降低VRE的作用,需要肠道Muribaculum ininale菌株,但需要其他6株菌株中至少有一株存在。7株上清液单独或联合使用均不抑制VRE体外生长。有趣的是,五种菌株属于人类和小鼠共有的物种,另外两种具有人类功能等同。结论:一种基于微生物群组成数学建模的创新方法可以识别共生菌株的混合物,从而提高对VRE的生态屏障效应。其机制取决于微生物群的恢复和初始组成。最终,这项工作将通过针对具有感染风险的易感患者,如中性粒细胞减少或骨髓移植患者,以及可能对补充共生菌株有反应的患者,实现个性化药物的发展,提供新的活体生物治疗产品和生物标志物来预测对补充的反应。视频摘要。
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来源期刊
Microbiome
Microbiome MICROBIOLOGY-
CiteScore
21.90
自引率
2.60%
发文量
198
审稿时长
4 weeks
期刊介绍: Microbiome is a journal that focuses on studies of microbiomes in humans, animals, plants, and the environment. It covers both natural and manipulated microbiomes, such as those in agriculture. The journal is interested in research that uses meta-omics approaches or novel bioinformatics tools and emphasizes the community/host interaction and structure-function relationship within the microbiome. Studies that go beyond descriptive omics surveys and include experimental or theoretical approaches will be considered for publication. The journal also encourages research that establishes cause and effect relationships and supports proposed microbiome functions. However, studies of individual microbial isolates/species without exploring their impact on the host or the complex microbiome structures and functions will not be considered for publication. Microbiome is indexed in BIOSIS, Current Contents, DOAJ, Embase, MEDLINE, PubMed, PubMed Central, and Science Citations Index Expanded.
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