粪便微生物群移植改变了艾滋病病毒炎症的蛋白质组景观:确定细菌驱动因素。

IF 13.8 1区 生物学 Q1 MICROBIOLOGY Microbiome Pub Date : 2024-10-22 DOI:10.1186/s40168-024-01919-5
Claudio Díaz-García, Elena Moreno, Alba Talavera-Rodríguez, Lucía Martín-Fernández, Sara González-Bodí, Laura Martín-Pedraza, José A Pérez-Molina, Fernando Dronda, María José Gosalbes, Laura Luna, María Jesús Vivancos, Jaime Huerta-Cepas, Santiago Moreno, Sergio Serrano-Villar
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引用次数: 0

摘要

背景:尽管抗逆转录病毒疗法有效,但艾滋病病毒感染者(PWH)仍会出现持续的全身炎症,发病率和死亡率也会增加。通过粪便微生物群移植(FMT)调节肠道微生物群是一种新的治疗策略。我们的目的是评估反复低剂量 FMT 与安慰剂对比后炎症通路的蛋白质组变化:这项双掩蔽、安慰剂对照试验研究评估了 29 名接受稳定抗逆转录病毒疗法(ART)的感染者在接受为期 8 周的每周 FMT 与安慰剂治疗后,蛋白质组对全身炎症的影响。研究人员选择了三位粪便细菌和丁酸盐含量较高的粪便捐献者,并将他们的粪便用于 FMT 胶囊的制备。在基线期、第 1 周、第 8 周和第 24 周收集的样本中,使用近距离延伸测定法量化了血浆中 345 种炎症蛋白的蛋白质组变化。同时,我们还通过散弹枪元基因组学分析了肠道微生物群组成的变化和功能注释。我们拟合了广义加性模型来评估蛋白质表达的动态变化。我们选择了最相关的蛋白质,使用线性混合模型探讨它们与微生物群组成和功能随时间变化的相关性:结果:FMT 能明显降低 45 种炎症蛋白的血浆水平,包括 IL6 和 TNF-α 等已确定的死亡率预测因子。我们发现,在最后一次 FMT 过程结束后的 16 周内,包括 CCL20 和 CD22 等蛋白的表达在内的炎症蛋白水平仍有明显下降。我们发现了46种蛋白质的变化,包括FT3LG、IL6、IL10RB、IL12B和IL17A的减少,这与多种细菌种类有关。我们发现,反刍球菌科、琥珀酰菌科、普雷沃特菌科和梭菌属中的特定细菌种类及其相关基因和功能与炎症标志物的变化显著相关:结论:通过 FMT 以肠道微生物组为靶点,可有效降低 PWH 的炎症蛋白,且效果持久。这些研究结果表明,微生物组有可能成为减轻该人群炎症相关并发症的治疗靶点,从而鼓励人们进一步研究和开发基于微生物组的干预措施。视频摘要。
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Fecal microbiota transplantation alters the proteomic landscape of inflammation in HIV: identifying bacterial drivers.

Background: Despite effective antiretroviral therapy, people with HIV (PWH) experience persistent systemic inflammation and increased morbidity and mortality. Modulating the gut microbiome through fecal microbiota transplantation (FMT) represents a novel therapeutic strategy. We aimed to evaluate proteomic changes in inflammatory pathways following repeated, low-dose FMT versus placebo.

Methods: This double-masked, placebo-controlled pilot study assessed the proteomic impacts of weekly FMT versus placebo treatment over 8 weeks on systemic inflammation in 29 PWH receiving stable antiretroviral therapy (ART). Three stool donors with high Faecalibacterium and butyrate profiles were selected, and their individual stools were used for FMT capsule preparation. Proteomic changes in 345 inflammatory proteins in plasma were quantified using the proximity extension assay, with samples collected at baseline and at weeks 1, 8, and 24. Concurrently, we characterized shifts in the gut microbiota composition and annotated functions through shotgun metagenomics. We fitted generalized additive models to evaluate the dynamics of protein expression. We selected the most relevant proteins to explore their correlations with microbiome composition and functionality over time using linear mixed models.

Results: FMT significantly reduced the plasma levels of 45 inflammatory proteins, including established mortality predictors such as IL6 and TNF-α. We found notable reductions persisting up to 16 weeks after the final FMT procedure, including in the expression of proteins such as CCL20 and CD22. We identified changes in 46 proteins, including decreases in FT3LG, IL6, IL10RB, IL12B, and IL17A, which correlated with multiple bacterial species. We found that specific bacterial species within the Ruminococcaceae, Succinivibrionaceae, Prevotellaceae families, and the Clostridium genus, in addition to their associated genes and functions, were significantly correlated with changes in inflammatory markers.

Conclusions: Targeting the gut microbiome through FMT effectively decreased inflammatory proteins in PWH, with sustained effects. These findings suggest the potential of the microbiome as a therapeutic target to mitigate inflammation-related complications in this population, encouraging further research and development of microbiome-based interventions. Video Abstract.

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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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