Gut microbiota metabolically mediate intestinal helminth infection in zebrafish.

IF 5 2区 生物学 Q1 MICROBIOLOGY mSystems Pub Date : 2024-09-17 Epub Date: 2024-08-27 DOI:10.1128/msystems.00545-24
Austin J Hammer, Christopher A Gaulke, Manuel Garcia-Jaramillo, Connor Leong, Jeffrey Morre, Michael J Sieler, Jan F Stevens, Yuan Jiang, Claudia S Maier, Michael L Kent, Thomas J Sharpton
{"title":"Gut microbiota metabolically mediate intestinal helminth infection in zebrafish.","authors":"Austin J Hammer, Christopher A Gaulke, Manuel Garcia-Jaramillo, Connor Leong, Jeffrey Morre, Michael J Sieler, Jan F Stevens, Yuan Jiang, Claudia S Maier, Michael L Kent, Thomas J Sharpton","doi":"10.1128/msystems.00545-24","DOIUrl":null,"url":null,"abstract":"<p><p>Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe <i>Pelomonas</i>, as a potent anthelmintic with activity against <i>Pseudocapillaria tomentosa</i> egg hatching, both <i>in vitro</i> and <i>in vivo</i>. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.</p><p><strong>Importance: </strong>Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.</p>","PeriodicalId":18819,"journal":{"name":"mSystems","volume":null,"pages":null},"PeriodicalIF":5.0000,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11406965/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"mSystems","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1128/msystems.00545-24","RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/8/27 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"MICROBIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

Intestinal helminth parasite (IHP) infection induces alterations in the composition of microbial communities across vertebrates, although how gut microbiota may facilitate or hinder parasite infection remains poorly defined. In this work, we utilized a zebrafish model to investigate the relationship between gut microbiota, gut metabolites, and IHP infection. We found that extreme disparity in zebrafish parasite infection burden is linked to the composition of the gut microbiome and that changes in the gut microbiome are associated with variation in a class of endogenously produced signaling compounds, N-acylethanolamines, that are known to be involved in parasite infection. Using a statistical mediation analysis, we uncovered a set of gut microbes whose relative abundance explains the association between gut metabolites and infection outcomes. Experimental investigation of one of the compounds in this analysis reveals salicylaldehyde, which is putatively produced by the gut microbe Pelomonas, as a potent anthelmintic with activity against Pseudocapillaria tomentosa egg hatching, both in vitro and in vivo. Collectively, our findings underscore the importance of the gut microbiome as a mediating agent in parasitic infection and highlight specific gut metabolites as tools for the advancement of novel therapeutic interventions against IHP infection.

Importance: Intestinal helminth parasites (IHPs) impact human health globally and interfere with animal health and agricultural productivity. While anthelmintics are critical to controlling parasite infections, their efficacy is increasingly compromised by drug resistance. Recent investigations suggest the gut microbiome might mediate helminth infection dynamics. So, identifying how gut microbes interact with parasites could yield new therapeutic targets for infection prevention and management. We conducted a study using a zebrafish model of parasitic infection to identify routes by which gut microbes might impact helminth infection outcomes. Our research linked the gut microbiome to both parasite infection and to metabolites in the gut to understand how microbes could alter parasite infection. We identified a metabolite in the gut, salicylaldehyde, that is putatively produced by a gut microbe and that inhibits parasitic egg growth. Our results also point to a class of compounds, N-acyl-ethanolamines, which are affected by changes in the gut microbiome and are linked to parasite infection. Collectively, our results indicate the gut microbiome may be a source of novel anthelmintics that can be harnessed to control IHPs.

查看原文
分享 分享
微信好友 朋友圈 QQ好友 复制链接
本刊更多论文
肠道微生物群在代谢上介导斑马鱼的肠道蠕虫感染。
肠道蠕虫寄生虫(IHP)感染会引起脊椎动物体内微生物群落组成的改变,但肠道微生物群如何促进或阻碍寄生虫感染仍未明确。在这项研究中,我们利用斑马鱼模型研究了肠道微生物群、肠道代谢物和 IHP 感染之间的关系。我们发现,斑马鱼寄生虫感染负担的极端差异与肠道微生物群的组成有关,而肠道微生物群的变化与内源性产生的一类信号化合物(N-乙酰乙醇胺)的变化有关,这些化合物已知与寄生虫感染有关。通过统计中介分析,我们发现了一组肠道微生物,它们的相对丰度可以解释肠道代谢物与感染结果之间的关联。通过对该分析中的一种化合物进行实验研究,我们发现水杨醛是一种有效的驱虫药,在体外和体内都能有效地抑制拟尾柱虫卵的孵化。总之,我们的研究结果强调了肠道微生物组作为寄生虫感染介导因子的重要性,并突出了特定肠道代谢物作为推进针对 IHP 感染的新型治疗干预工具的重要性:肠道蠕虫寄生虫(IHPs)在全球范围内影响人类健康,并干扰动物健康和农业生产力。虽然抗蠕虫药对控制寄生虫感染至关重要,但其疗效却因耐药性而日益受损。最近的研究表明,肠道微生物组可能会介导蠕虫感染的动态变化。因此,确定肠道微生物如何与寄生虫相互作用,可以为预防和控制感染提供新的治疗目标。我们利用斑马鱼寄生虫感染模型进行了一项研究,以确定肠道微生物可能影响蠕虫感染结果的途径。我们的研究将肠道微生物组与寄生虫感染和肠道中的代谢物联系起来,以了解微生物如何改变寄生虫感染。我们在肠道中发现了一种代谢物--水杨醛,它可能是由肠道微生物产生的,能抑制寄生虫卵的生长。我们的研究结果还发现了一类化合物--N-乙酰乙醇胺,它受肠道微生物群变化的影响,并与寄生虫感染有关。总之,我们的研究结果表明,肠道微生物组可能是新型抗蠕虫药物的来源,可用于控制国际水文计划。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 去求助
来源期刊
mSystems
mSystems Biochemistry, Genetics and Molecular Biology-Biochemistry
CiteScore
10.50
自引率
3.10%
发文量
308
审稿时长
13 weeks
期刊介绍: mSystems™ will publish preeminent work that stems from applying technologies for high-throughput analyses to achieve insights into the metabolic and regulatory systems at the scale of both the single cell and microbial communities. The scope of mSystems™ encompasses all important biological and biochemical findings drawn from analyses of large data sets, as well as new computational approaches for deriving these insights. mSystems™ will welcome submissions from researchers who focus on the microbiome, genomics, metagenomics, transcriptomics, metabolomics, proteomics, glycomics, bioinformatics, and computational microbiology. mSystems™ will provide streamlined decisions, while carrying on ASM''s tradition of rigorous peer review.
期刊最新文献
Effect of combined probiotics and doxycycline therapy on the gut-skin axis in rosacea. Stable, multigenerational transmission of the bean seed microbiome despite abiotic stress. Antimicrobial and antibiofilm activity of human recombinant H1 histones against bacterial infections. Gut and oral microbial compositional differences in women with breast cancer, women with ductal carcinoma in situ, and healthy women. Metagenomic sequencing of CRISPRs as a new marker to aid in personal identification with low-biomass samples.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
已复制链接
已复制链接
快去分享给好友吧!
我知道了
×
扫码分享
扫码分享
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1