McDonnell Genome Institute, Washington University, St. Louis, MO, 63108, USA.
Department of Parasitology, Faculty of Medicine, Universitas Indonesia, Jakarta, Indonesia.
Microbiome. 2018 Feb 28;6(1):33. doi: 10.1186/s40168-018-0416-5.
The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood.
A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state. The microbiomes of individuals able to self-clear the infection had more alike microbiome assemblages compared to individuals who remained infected. One bacterial taxon (Lachnospiracae) was negatively associated with infection in both countries, and 12 bacterial taxa were significantly associated with STH infection in both countries, including Olsenella (associated with reduced gut inflammation), which also significantly reduced in abundance following clearance of infection. Microbial community gene abundances were also affected by deworming. Functional categories identified as associated with STH infection included arachidonic acid metabolism; arachidonic acid is the precursor for pro-inflammatory leukotrienes that threaten helminth survival, and our findings suggest that some modulation of arachidonic acid activity in the STH-infected gut may occur through the increase of arachidonic acid metabolizing bacteria.
For the first time, we identify specific members of the gut microbiome that discriminate between moderately/heavily STH-infected and non-infected states across very diverse geographical regions using two different statistical methods. We also identify microbiome-encoded biological functions associated with the STH infections, which are associated potentially with STH survival strategies, and changes in the host environment. These results provide a novel insight of the cross-kingdom interactions in the human gut ecosystem by unlocking the microbiome assemblages at taxonomic, genetic, and functional levels so that advances towards key mechanistic studies can be made.
人类肠道及其微生物群是土壤传播性蠕虫(STH)最常见的感染部位,全球约有 15 亿人受到影响。复杂的跨领域相互作用尚未得到很好的理解。
横断面分析在利比里亚和印度尼西亚确定了与 STH 感染呈正相关或负相关的保守微生物特征,并且来自双盲随机试验的纵向样本分析表明,肠道微生物群对驱虫有反应,但不会更接近未感染状态。能够自行清除感染的个体的微生物组具有更相似的微生物组组合,而那些持续感染的个体则不同。在两个国家中,一个细菌分类群(Lachnospiracae)与感染呈负相关,并且有 12 个细菌分类群与 STH 感染显著相关,包括与减少肠道炎症相关的 Olsenella,在清除感染后其丰度也显著降低。微生物群落基因丰度也受到驱虫的影响。确定与 STH 感染相关的功能类别包括花生四烯酸代谢;花生四烯酸是促炎白三烯的前体,白三烯威胁着蠕虫的生存,我们的研究结果表明,在 STH 感染的肠道中,花生四烯酸活性可能通过增加花生四烯酸代谢细菌而发生一些调节。
我们首次使用两种不同的统计方法,在非常不同的地理区域内,确定了可区分中度/重度 STH 感染和非感染状态的肠道微生物组的特定成员。我们还确定了与 STH 感染相关的微生物组编码生物功能,这些功能与 STH 的生存策略以及宿主环境的变化有关。这些结果通过在分类、遗传和功能水平上解锁微生物组组合,提供了对人类肠道生态系统中跨领域相互作用的新见解,从而为关键机制研究的进展奠定了基础。