Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.

Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treate...

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Autores principales:	Mara Jana Broadhurst, Amir Ardeshir, Bittoo Kanwar, Julie Mirpuri, Uma Mahesh Gundra, Jacqueline M Leung, Kirsten E Wiens, Ivan Vujkovic-Cvijin, Charlie C Kim, Felix Yarovinsky, Nicholas W Lerche, Joseph M McCune, P'ng Loke
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2012
Materias:	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/0f8380b17577473c9486011ba2e6848e
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spelling	oai:doaj.org-article:0f8380b17577473c9486011ba2e6848e2021-11-18T06:06:22ZTherapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.1553-73661553-737410.1371/journal.ppat.1003000https://doaj.org/article/0f8380b17577473c9486011ba2e6848e2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23166490/?tool=EBIhttps://doaj.org/toc/1553-7366https://doaj.org/toc/1553-7374Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.Mara Jana BroadhurstAmir ArdeshirBittoo KanwarJulie MirpuriUma Mahesh GundraJacqueline M LeungKirsten E WiensIvan Vujkovic-CvijinCharlie C KimFelix YarovinskyNicholas W LercheJoseph M McCuneP'ng LokePublic Library of Science (PLoS)articleImmunologic diseases. AllergyRC581-607Biology (General)QH301-705.5ENPLoS Pathogens, Vol 8, Iss 11, p e1003000 (2012)
institution	DOAJ
collection	DOAJ
language	EN
topic	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5
spellingShingle	Immunologic diseases. Allergy RC581-607 Biology (General) QH301-705.5 Mara Jana Broadhurst Amir Ardeshir Bittoo Kanwar Julie Mirpuri Uma Mahesh Gundra Jacqueline M Leung Kirsten E Wiens Ivan Vujkovic-Cvijin Charlie C Kim Felix Yarovinsky Nicholas W Lerche Joseph M McCune P'ng Loke Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
description	Idiopathic chronic diarrhea (ICD) is a leading cause of morbidity amongst rhesus monkeys kept in captivity. Here, we show that exposure of affected animals to the whipworm Trichuris trichiura led to clinical improvement in fecal consistency, accompanied by weight gain, in four out of the five treated monkeys. By flow cytometry analysis of pinch biopsies collected during colonoscopies before and after treatment, we found an induction of a mucosal T(H)2 response following helminth treatment that was associated with a decrease in activated CD4(+) Ki67+ cells. In parallel, expression profiling with oligonucleotide microarrays and real-time PCR analysis revealed reductions in T(H)1-type inflammatory gene expression and increased expression of genes associated with IgE signaling, mast cell activation, eosinophil recruitment, alternative activation of macrophages, and worm expulsion. By quantifying bacterial 16S rRNA in pinch biopsies using real-time PCR analysis, we found reduced bacterial attachment to the intestinal mucosa post-treatment. Finally, deep sequencing of bacterial 16S rRNA revealed changes to the composition of microbial communities attached to the intestinal mucosa following helminth treatment. Thus, the genus Streptophyta of the phylum Cyanobacteria was vastly increased in abundance in three out of five ICD monkeys relative to healthy controls, but was reduced to control levels post-treatment; by contrast, the phylum Tenericutes was expanded post-treatment. These findings suggest that helminth treatment in primates can ameliorate colitis by restoring mucosal barrier functions and reducing overall bacterial attachment, and also by altering the communities of attached bacteria. These results also define ICD in monkeys as a tractable preclinical model for ulcerative colitis in which these effects can be further investigated.
format	article
author	Mara Jana Broadhurst Amir Ardeshir Bittoo Kanwar Julie Mirpuri Uma Mahesh Gundra Jacqueline M Leung Kirsten E Wiens Ivan Vujkovic-Cvijin Charlie C Kim Felix Yarovinsky Nicholas W Lerche Joseph M McCune P'ng Loke
author_facet	Mara Jana Broadhurst Amir Ardeshir Bittoo Kanwar Julie Mirpuri Uma Mahesh Gundra Jacqueline M Leung Kirsten E Wiens Ivan Vujkovic-Cvijin Charlie C Kim Felix Yarovinsky Nicholas W Lerche Joseph M McCune P'ng Loke
author_sort	Mara Jana Broadhurst
title	Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
title_short	Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
title_full	Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
title_fullStr	Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
title_full_unstemmed	Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
title_sort	therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.
publisher	Public Library of Science (PLoS)
publishDate	2012
url	https://doaj.org/article/0f8380b17577473c9486011ba2e6848e
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Therapeutic helminth infection of macaques with idiopathic chronic diarrhea alters the inflammatory signature and mucosal microbiota of the colon.

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