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实验感染美洲钩虫(Necator americanus)与复发性多发性硬化症人类志愿者的稳定肠道微生物多样性有关。

Experimental infection with the hookworm, Necator americanus, is associated with stable gut microbial diversity in human volunteers with relapsing multiple sclerosis.

机构信息

Department of Veterinary Medicine, University of Cambridge, Cambridge, UK.

Present address: Department of Biotechnology and Biomedicine, Technical University of Denmark, Kongens Lyngby, Denmark.

出版信息

BMC Biol. 2021 Apr 14;19(1):74. doi: 10.1186/s12915-021-01003-6.

DOI:10.1186/s12915-021-01003-6
PMID:33853585
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8048248/
Abstract

BACKGROUND

Helminth-associated changes in gut microbiota composition have been hypothesised to contribute to the immune-suppressive properties of parasitic worms. Multiple sclerosis is an immune-mediated autoimmune disease of the central nervous system whose pathophysiology has been linked to imbalances in gut microbial communities.

RESULTS

In the present study, we investigated, for the first time, qualitative and quantitative changes in the faecal bacterial composition of human volunteers with remitting multiple sclerosis (RMS) prior to and following experimental infection with the human hookworm, Necator americanus (N+), and following anthelmintic treatment, and compared the findings with data obtained from a cohort of RMS patients subjected to placebo treatment (PBO). Bacterial 16S rRNA high-throughput sequencing data revealed significantly decreased alpha diversity in the faecal microbiota of PBO compared to N+ subjects over the course of the trial; additionally, we observed significant differences in the abundances of several bacterial taxa with putative immune-modulatory functions between study cohorts. Parabacteroides were significantly expanded in the faecal microbiota of N+ individuals for which no clinical and/or radiological relapses were recorded at the end of the trial.

CONCLUSIONS

Overall, our data lend support to the hypothesis of a contributory role of parasite-associated alterations in gut microbial composition to the immune-modulatory properties of hookworm parasites.

摘要

背景

肠道微生物组成中与寄生虫相关的变化被假设为有助于寄生虫的免疫抑制特性。多发性硬化症是一种中枢神经系统的免疫介导自身免疫性疾病,其病理生理学与肠道微生物群落的失衡有关。

结果

在本研究中,我们首次研究了缓解期多发性硬化症(RMS)患者在接受人体钩虫(Necator americanus,N+)实验感染前后以及驱虫治疗后的粪便细菌组成的定性和定量变化,并将研究结果与接受安慰剂治疗(PBO)的 RMS 患者队列的数据进行了比较。细菌 16S rRNA 高通量测序数据显示,与 N+组相比,PBO 组在试验过程中粪便微生物群的 alpha 多样性显著降低;此外,我们还观察到两个研究队列之间具有潜在免疫调节功能的几个细菌分类群的丰度存在显著差异。在试验结束时没有记录到临床和/或放射学复发的 N+个体的粪便微生物群中,拟杆菌显著扩增。

结论

总体而言,我们的数据支持寄生虫相关的肠道微生物组成变化有助于钩虫寄生虫的免疫调节特性的假设。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/196468f2569f/12915_2021_1003_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/94bd7e293589/12915_2021_1003_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/8e1c1776f5ec/12915_2021_1003_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/84265fbf3a65/12915_2021_1003_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/906cee540791/12915_2021_1003_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/25fbbf21bbd1/12915_2021_1003_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/5d044f46db8e/12915_2021_1003_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/0a943fc7be0d/12915_2021_1003_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/9f99ec19f01b/12915_2021_1003_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/196468f2569f/12915_2021_1003_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/94bd7e293589/12915_2021_1003_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/8e1c1776f5ec/12915_2021_1003_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/84265fbf3a65/12915_2021_1003_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/906cee540791/12915_2021_1003_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/25fbbf21bbd1/12915_2021_1003_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/5d044f46db8e/12915_2021_1003_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/0a943fc7be0d/12915_2021_1003_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/9f99ec19f01b/12915_2021_1003_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/871d/8048248/196468f2569f/12915_2021_1003_Fig9_HTML.jpg

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