Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine
Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the...
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creator | Partida-Rodríguez, Oswaldo Brown, Eric M Woodward, Sarah E Cirstea, Mihai Reynolds, Lisa A Petersen, Charisse Vogt, Stefanie L Peña-Díaz, Jorge Thorson, Lisa Arrieta, Marie-Claire Hernández, Eric G Rojas-Velázquez, Liliana Moran, Patricia González Rivas, Enrique Serrano-Vázquez, Angélica Pérez-Juárez, Horacio Torres, Javier Ximénez, Cecilia Finlay, B B |
description | Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans. |
doi_str_mv | 10.1371/journal.pone.0312775 |
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However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0312775</identifier><identifier>PMID: 39466773</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Analysis ; Animal models ; Animals ; Asymptomatic ; Bacteria ; Biology and Life Sciences ; Care and treatment ; CD3 antigen ; CD4 antigen ; Colon ; Colorectal diseases ; Cytokines ; Cytokines - metabolism ; Diagnosis ; Digestive system ; Down-Regulation ; Duodenum ; E coli ; Fecal Microbiota Transplantation ; Fecal microflora ; Feces ; Female ; Foxp3 protein ; Gastrointestinal diseases ; Gastrointestinal Microbiome - immunology ; Gastrointestinal tract ; Germ-Free Life ; Germfree ; Health aspects ; Health care ; Homeostasis ; Ileum ; Immune response ; Immune system ; Immunity (Disease) ; Immunology ; Immunoregulation ; Infections ; Inflammation ; Inflammatory bowel disease ; Interleukins ; Intestinal microflora ; Intestinal Mucosa - immunology ; Intestinal Mucosa - metabolism ; Intestinal parasites ; Intestine ; Intestines - immunology ; Intestines - microbiology ; Intestines - parasitology ; Lymphocytes ; Lymphocytes T ; Medicine and Health Sciences ; Mice ; Mice, Inbred C57BL ; Microbiota ; Microbiota (Symbiotic organisms) ; Microorganisms ; Monocyte chemoattractant protein 1 ; Mothers ; Parasites ; Population genetics ; Proteins ; Protozoa ; Research and Analysis Methods ; Small intestine ; Spleen ; Spleen - immunology ; Spleen - metabolism ; T-Lymphocytes, Regulatory - immunology ; Thickness</subject><ispartof>PloS one, 2024-10, Vol.19 (10), p.e0312775</ispartof><rights>Copyright: © 2024 Partida-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.</rights><rights>COPYRIGHT 2024 Public Library of Science</rights><rights>2024 Partida-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 Partida-Rodríguez et al 2024 Partida-Rodríguez et al</rights><rights>2024 Partida-Rodríguez et al. This is an open access article distributed under the terms of the Creative Commons Attribution License: http://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c572t-84337cea3c3949f4fe95a90c5a474fb283a30fe4c51790c491df3e25b71a31a43</cites><orcidid>0000-0002-0393-5712 ; 0000-0003-0574-4538 ; 0000-0002-9211-240X ; 0000-0002-6688-0595</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515975/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11515975/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39466773$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Partida-Rodríguez, Oswaldo</creatorcontrib><creatorcontrib>Brown, Eric M</creatorcontrib><creatorcontrib>Woodward, Sarah E</creatorcontrib><creatorcontrib>Cirstea, Mihai</creatorcontrib><creatorcontrib>Reynolds, Lisa A</creatorcontrib><creatorcontrib>Petersen, Charisse</creatorcontrib><creatorcontrib>Vogt, Stefanie L</creatorcontrib><creatorcontrib>Peña-Díaz, Jorge</creatorcontrib><creatorcontrib>Thorson, Lisa</creatorcontrib><creatorcontrib>Arrieta, Marie-Claire</creatorcontrib><creatorcontrib>Hernández, Eric G</creatorcontrib><creatorcontrib>Rojas-Velázquez, Liliana</creatorcontrib><creatorcontrib>Moran, Patricia</creatorcontrib><creatorcontrib>González Rivas, Enrique</creatorcontrib><creatorcontrib>Serrano-Vázquez, Angélica</creatorcontrib><creatorcontrib>Pérez-Juárez, Horacio</creatorcontrib><creatorcontrib>Torres, Javier</creatorcontrib><creatorcontrib>Ximénez, Cecilia</creatorcontrib><creatorcontrib>Finlay, B B</creatorcontrib><title>Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.</description><subject>Analysis</subject><subject>Animal models</subject><subject>Animals</subject><subject>Asymptomatic</subject><subject>Bacteria</subject><subject>Biology and Life Sciences</subject><subject>Care and treatment</subject><subject>CD3 antigen</subject><subject>CD4 antigen</subject><subject>Colon</subject><subject>Colorectal diseases</subject><subject>Cytokines</subject><subject>Cytokines - metabolism</subject><subject>Diagnosis</subject><subject>Digestive system</subject><subject>Down-Regulation</subject><subject>Duodenum</subject><subject>E coli</subject><subject>Fecal Microbiota Transplantation</subject><subject>Fecal microflora</subject><subject>Feces</subject><subject>Female</subject><subject>Foxp3 protein</subject><subject>Gastrointestinal 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microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine</title><author>Partida-Rodríguez, Oswaldo ; Brown, Eric M ; Woodward, Sarah E ; Cirstea, Mihai ; Reynolds, Lisa A ; Petersen, Charisse ; Vogt, Stefanie L ; Peña-Díaz, Jorge ; Thorson, Lisa ; Arrieta, Marie-Claire ; Hernández, Eric G ; Rojas-Velázquez, Liliana ; Moran, Patricia ; González Rivas, Enrique ; Serrano-Vázquez, Angélica ; Pérez-Juárez, Horacio ; Torres, Javier ; Ximénez, Cecilia ; Finlay, B B</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c572t-84337cea3c3949f4fe95a90c5a474fb283a30fe4c51790c491df3e25b71a31a43</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Analysis</topic><topic>Animal models</topic><topic>Animals</topic><topic>Asymptomatic</topic><topic>Bacteria</topic><topic>Biology and 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bowel disease</topic><topic>Interleukins</topic><topic>Intestinal microflora</topic><topic>Intestinal Mucosa - immunology</topic><topic>Intestinal Mucosa - metabolism</topic><topic>Intestinal parasites</topic><topic>Intestine</topic><topic>Intestines - immunology</topic><topic>Intestines - microbiology</topic><topic>Intestines - parasitology</topic><topic>Lymphocytes</topic><topic>Lymphocytes T</topic><topic>Medicine and Health Sciences</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>Microbiota</topic><topic>Microbiota (Symbiotic organisms)</topic><topic>Microorganisms</topic><topic>Monocyte chemoattractant protein 1</topic><topic>Mothers</topic><topic>Parasites</topic><topic>Population genetics</topic><topic>Proteins</topic><topic>Protozoa</topic><topic>Research and Analysis Methods</topic><topic>Small intestine</topic><topic>Spleen</topic><topic>Spleen - immunology</topic><topic>Spleen - metabolism</topic><topic>T-Lymphocytes, Regulatory - immunology</topic><topic>Thickness</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Partida-Rodríguez, Oswaldo</creatorcontrib><creatorcontrib>Brown, Eric M</creatorcontrib><creatorcontrib>Woodward, Sarah E</creatorcontrib><creatorcontrib>Cirstea, Mihai</creatorcontrib><creatorcontrib>Reynolds, Lisa A</creatorcontrib><creatorcontrib>Petersen, Charisse</creatorcontrib><creatorcontrib>Vogt, Stefanie L</creatorcontrib><creatorcontrib>Peña-Díaz, Jorge</creatorcontrib><creatorcontrib>Thorson, Lisa</creatorcontrib><creatorcontrib>Arrieta, Marie-Claire</creatorcontrib><creatorcontrib>Hernández, Eric G</creatorcontrib><creatorcontrib>Rojas-Velázquez, Liliana</creatorcontrib><creatorcontrib>Moran, Patricia</creatorcontrib><creatorcontrib>González Rivas, Enrique</creatorcontrib><creatorcontrib>Serrano-Vázquez, Angélica</creatorcontrib><creatorcontrib>Pérez-Juárez, Horacio</creatorcontrib><creatorcontrib>Torres, Javier</creatorcontrib><creatorcontrib>Ximénez, Cecilia</creatorcontrib><creatorcontrib>Finlay, B B</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Opposing Viewpoints</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Animal Behavior Abstracts</collection><collection>Bacteriology Abstracts (Microbiology B)</collection><collection>Biotechnology Research Abstracts</collection><collection>Nursing & Allied Health Database</collection><collection>Ecology Abstracts</collection><collection>Entomology Abstracts (Full archive)</collection><collection>Immunology Abstracts</collection><collection>Meteorological & Geoastrophysical Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Agricultural Science Collection</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Technology Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Materials Science & Engineering Collection</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One 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Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Materials Science Database</collection><collection>Nursing & Allied Health Database (Alumni Edition)</collection><collection>Meteorological & Geoastrophysical Abstracts - Academic</collection><collection>ProQuest Engineering Collection</collection><collection>ProQuest Biological Science Collection</collection><collection>Agricultural Science Database</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Biological Science Database</collection><collection>Engineering Database</collection><collection>Nursing & Allied Health Premium</collection><collection>Advanced Technologies & Aerospace Database</collection><collection>ProQuest Advanced Technologies & Aerospace Collection</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Environmental Science Database</collection><collection>Materials Science Collection</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>Engineering Collection</collection><collection>Environmental Science Collection</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Partida-Rodríguez, Oswaldo</au><au>Brown, Eric M</au><au>Woodward, Sarah E</au><au>Cirstea, Mihai</au><au>Reynolds, Lisa A</au><au>Petersen, Charisse</au><au>Vogt, Stefanie L</au><au>Peña-Díaz, Jorge</au><au>Thorson, Lisa</au><au>Arrieta, Marie-Claire</au><au>Hernández, Eric G</au><au>Rojas-Velázquez, Liliana</au><au>Moran, Patricia</au><au>González Rivas, Enrique</au><au>Serrano-Vázquez, Angélica</au><au>Pérez-Juárez, Horacio</au><au>Torres, Javier</au><au>Ximénez, Cecilia</au><au>Finlay, B B</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2024-10-28</date><risdate>2024</risdate><volume>19</volume><issue>10</issue><spage>e0312775</spage><pages>e0312775-</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Intestinal parasites are part of the intestinal ecosystem and have been shown to establish close interactions with the intestinal microbiota. However, little is known about the influence of intestinal protozoa on the regulation of the immune response. In this study, we analyzed the regulation of the immune response of germ-free mice transplanted with fecal microbiota (FMT) from individuals with multiple parasitic protozoans (P) and non-parasitized individuals (NP). We determined the production of intestinal cytokines, the lymphocyte populations in both the colon and the spleen, and the genetic expression of markers of intestinal epithelial integrity. We observed a general downregulation of the intestinal immune response in mice receiving FMT-P. We found significantly lower intestinal production of the cytokines IL-6, TNF, IFN-γ, MCP-1, IL-10, and IL-12 in the FMT-P. Furthermore, a significant decrease in the proportion of CD3+, CD4+, and Foxp3+ T regulatory cells (Treg) was observed in both, the colon and spleen with FMT-P in contrast to FMT-NP. We also found that in FMT-P mice there was a significant decrease in tjp1 expression in all three regions of the small intestine; ocln in the ileum; reg3γ in the duodenum and relmβ in both the duodenum and ileum. We also found an increase in colonic mucus layer thickness in mice colonized with FMT-P in contrast with FMT-NP. Finally, our results suggest that gut protozoa, such as Blastocystis hominis, Entamoeba coli, Endolimax nana, Entamoeba histolytica/E. dispar, Iodamoeba bütschlii, and Chilomastix mesnili consortia affect the immunoinflammatory state and induce functional changes in the intestine via the gut microbiota. Likewise, it allows us to establish an FMT model in germ-free mice as a viable alternative to explore the effects that exposure to intestinal parasites could have on the immune response in humans.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>39466773</pmid><doi>10.1371/journal.pone.0312775</doi><tpages>e0312775</tpages><orcidid>https://orcid.org/0000-0002-0393-5712</orcidid><orcidid>https://orcid.org/0000-0003-0574-4538</orcidid><orcidid>https://orcid.org/0000-0002-9211-240X</orcidid><orcidid>https://orcid.org/0000-0002-6688-0595</orcidid><oa>free_for_read</oa></addata></record> |
fulltext | fulltext |
identifier | ISSN: 1932-6203 |
ispartof | PloS one, 2024-10, Vol.19 (10), p.e0312775 |
issn | 1932-6203 1932-6203 |
language | eng |
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source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
subjects | Analysis Animal models Animals Asymptomatic Bacteria Biology and Life Sciences Care and treatment CD3 antigen CD4 antigen Colon Colorectal diseases Cytokines Cytokines - metabolism Diagnosis Digestive system Down-Regulation Duodenum E coli Fecal Microbiota Transplantation Fecal microflora Feces Female Foxp3 protein Gastrointestinal diseases Gastrointestinal Microbiome - immunology Gastrointestinal tract Germ-Free Life Germfree Health aspects Health care Homeostasis Ileum Immune response Immune system Immunity (Disease) Immunology Immunoregulation Infections Inflammation Inflammatory bowel disease Interleukins Intestinal microflora Intestinal Mucosa - immunology Intestinal Mucosa - metabolism Intestinal parasites Intestine Intestines - immunology Intestines - microbiology Intestines - parasitology Lymphocytes Lymphocytes T Medicine and Health Sciences Mice Mice, Inbred C57BL Microbiota Microbiota (Symbiotic organisms) Microorganisms Monocyte chemoattractant protein 1 Mothers Parasites Population genetics Proteins Protozoa Research and Analysis Methods Small intestine Spleen Spleen - immunology Spleen - metabolism T-Lymphocytes, Regulatory - immunology Thickness |
title | Fecal microbiota transplantation from protozoa-exposed donors downregulates immune response in a germ-free mouse model, its role in immune response and physiology of the intestine |
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