Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques
Effects of Fecal Microbial Transplantation on Microbiome and Immunity in Simian Immunodeficiency Virus-Infected Macaques
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DOI：
10.1128/jvi.00099-16
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发表时间：
2016-05-01
影响因子：
5.4
通讯作者：
Klatt, Nichole R.
中科院分区：
文献类型：
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作者：
Hensley-McBain, Tiffany;Zevin, Alexander S.;Klatt, Nichole R.
慢性人类免疫缺陷病毒（HIV）感染期间肠道微生物组的改变与粘膜功能障碍、炎症和疾病进展相关。我们对粪便微生物群移植（FMT）作为HIV感染者的潜在治疗方法的安全性和有效性进行了临床前评估。抗逆转录病毒治疗，慢性猴免疫缺陷病毒（SIV）感染的恒河猴接受抗生素，然后FMT。抗生素治疗后观察到最大的微生物群变化。FMT后2周的细菌群落组成与FMT前的群落结构相似，但次要细菌种群丰度仍存在差异。免疫学上，我们观察到外周Th17和Th22细胞的数量显着增加，并减少CD4（+）T细胞活化的胃肠道组织后FMT。重要的是，移植耐受性良好，没有负面的临床副作用。虽然这项初步研究没有控制抗生素治疗和FMT对观察结果的不同贡献，但数据表明FMT可能具有有益作用，应在更大规模的研究中进一步评估。确定FMT的安全性对于防止有害后果至关重要，如果将来将其用作治疗的话。在这里，我们使用猕猴模型的HIV感染和FMT对6慢性SIV感染的恒河猴抗逆转录病毒治疗。除了提供FMT在感染慢病毒的灵长类动物中的安全性的临床前证明外，这项研究还提供了一个独特的机会来检查微生物组改变与免疫学参数之间的关系。在这项研究中，我们发现FMT后Th17和Th22细胞数量增加以及CD4（+）T细胞活化减少，这些变化在所有采样时间点与结肠中低丰度分类组和其他分类组的相关性最强。总的来说，这些数据提供了证据，表明微生物组的变化，特别是在少数群体的多样性和变化方面，可以增强免疫力，并且不会产生不良后果。
An altered intestinal microbiome during chronic human immunodeficiency virus (HIV) infection is associated with mucosal dysfunction, inflammation, and disease progression. We performed a preclinical evaluation of the safety and efficacy of fecal microbiota transplantation (FMT) as a potential therapeutic in HIV-infected individuals. Antiretroviral-treated, chronically simian immunodeficiency virus (SIV)-infected rhesus macaques received antibiotics followed by FMT. The greatest microbiota shift was observed after antibiotic treatment. The bacterial community composition at 2 weeks post-FMT resembled the pre-FMT community structure, although differences in the abundances of minor bacterial populations remained. Immunologically, we observed significant increases in the number of peripheral Th17 and Th22 cells and reduced CD4(+) T cell activation in gastrointestinal tissues post-FMT. Importantly, the transplant was well tolerated with no negative clinical side effects. Although this pilot study did not control for the differential contributions of antibiotic treatment and FMT to the observed results, the data suggest that FMT may have beneficial effects that should be further evaluated in larger studies.IMPORTANCEDue to the immunodeficiency and chronic inflammation that occurs during HIV infection, determination of the safety of FMT is crucial to prevent deleterious consequences if it is to be used as a treatment in the future. Here we used the macaque model of HIV infection and performed FMT on six chronically SIV-infected rhesus macaques on antiretroviral treatment. In addition to providing a preclinical demonstration of the safety of FMT in primates infected with a lentivirus, this study provided a unique opportunity to examine the relationships between alterations to the microbiome and immunological parameters. In this study, we found increased numbers of Th17 and Th22 cells as well as decreased activation of CD4(+) T cells post-FMT, and these changes correlated most strongly across all sampling time points with lower-abundance taxonomic groups and other taxonomic groups in the colon. Overall, these data provide evidence that changes in the microbiome, particularly in terms of diversity and changes in minor populations, can enhance immunity and do not have adverse consequences.