Table_5_Baseline Gut Microbiota Composition Is Associated With Schistosoma mansoni Infection Burden in Rodent Models.xlsx

In spite of growing evidence supporting the occurrence of complex interactions between Schistosoma and gut bacteria in mice and humans, no data is yet available on whether worm-mediated changes in microbiota composition are dependent on the baseline gut microbial profile of the vertebrate host. In addition, the impact of such changes on the susceptibility to, and pathophysiology of, schistosomiasis remains largely unexplored. In this study, mice colonized with gut microbial populations from a human donor (HMA mice), as well as microbiota-wild type (WT) animals, were infected with Schistosoma mansoni, and alterations of their gut microbial profiles at 50 days post-infection were compared to those occurring in uninfected HMA and WT rodents, respectively. Significantly higher worm and egg burdens, together with increased specific antibody responses to parasite antigens, were observed in HMA compared to WT mice. These differences were associated to extensive dissimilarities between the gut microbial profiles of each HMA and WT groups of mice at baseline; in particular, the gut microbiota of HMA animals was characterized by low microbial alpha diversity and expanded Proteobacteria, as well as by the absence of putative immunomodulatory bacteria (e.g. Lactobacillus). Furthermore, differences in infection-associated changes in gut microbiota composition were observed between HMA and WT mice. Altogether, our findings support the hypothesis that susceptibility to S.mansoni infection in mice is partially dependent on the composition of the host baseline microbiota. Moreover, this study highlights the applicability of HMA mouse models to address key biological questions on host-parasite-microbiota relationships in human helminthiases.

尽管已有越来越多的证据表明，小鼠与人类体内的血吸虫与肠道细菌之间存在复杂的相互作用，但目前尚无数据明确寄生虫介导的菌群组成改变是否依赖于脊椎动物宿主的基线肠道微生物谱。此外，此类改变对血吸虫病易感性及其病理生理学的影响，在很大程度上仍未得到探索。本研究中，我们将接受人类供体肠道菌群定植的小鼠（HMA小鼠，human microbiota-associated mice）以及野生型（WT）小鼠分别感染曼氏血吸虫（Schistosoma mansoni），并将感染后50天的肠道微生物谱变化，与未感染的HMA和WT啮齿类动物分别进行对比。与WT小鼠相比，HMA小鼠的成虫荷与虫卵荷均显著升高，且针对寄生虫抗原的特异性抗体应答也更强。这些差异与两组小鼠基线状态下肠道微生物谱的广泛差异密切相关；具体而言，HMA小鼠的肠道菌群以低微生物α多样性、丰度升高的变形菌门（Proteobacteria）为特征，且缺乏潜在的免疫调节性细菌（如乳杆菌属Lactobacillus）。此外，HMA与WT小鼠在感染相关的肠道菌群组成变化上也存在显著差异。综上，我们的研究结果支持以下假说：小鼠对曼氏血吸虫感染的易感性部分依赖于宿主的基线菌群组成。此外，本研究还证实了HMA小鼠模型可用于解答人类蠕虫病中宿主-寄生虫-菌群互作关系的关键科学问题。