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":"肠道微生物群在代谢上介导斑马鱼的肠道蠕虫感染。","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":"{\"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}","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}
Gut microbiota metabolically mediate intestinal helminth infection in zebrafish.
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.
mSystemsBiochemistry, 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.