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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: Broadhurst, Mara Jana, Ardeshir, Amir, Kanwar, Bittoo, Mirpuri, Julie, Gundra, Uma Mahesh, Leung, Jacqueline M., Wiens, Kirsten E., Vujkovic-Cvijin, Ivan, Kim, Charlie C., Yarovinsky, Felix, Lerche, Nicholas W., McCune, Joseph M., Loke, P'ng
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499566/
https://www.ncbi.nlm.nih.gov/pubmed/23166490
http://dx.doi.org/10.1371/journal.ppat.1003000
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author Broadhurst, Mara Jana
Ardeshir, Amir
Kanwar, Bittoo
Mirpuri, Julie
Gundra, Uma Mahesh
Leung, Jacqueline M.
Wiens, Kirsten E.
Vujkovic-Cvijin, Ivan
Kim, Charlie C.
Yarovinsky, Felix
Lerche, Nicholas W.
McCune, Joseph M.
Loke, P'ng
author_facet Broadhurst, Mara Jana
Ardeshir, Amir
Kanwar, Bittoo
Mirpuri, Julie
Gundra, Uma Mahesh
Leung, Jacqueline M.
Wiens, Kirsten E.
Vujkovic-Cvijin, Ivan
Kim, Charlie C.
Yarovinsky, Felix
Lerche, Nicholas W.
McCune, Joseph M.
Loke, P'ng
author_sort Broadhurst, Mara Jana
collection PubMed
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.
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spelling pubmed-34995662012-11-19 Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon Broadhurst, Mara Jana Ardeshir, Amir Kanwar, Bittoo Mirpuri, Julie Gundra, Uma Mahesh Leung, Jacqueline M. Wiens, Kirsten E. Vujkovic-Cvijin, Ivan Kim, Charlie C. Yarovinsky, Felix Lerche, Nicholas W. McCune, Joseph M. Loke, P'ng PLoS Pathog Research Article 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. Public Library of Science 2012-11-15 /pmc/articles/PMC3499566/ /pubmed/23166490 http://dx.doi.org/10.1371/journal.ppat.1003000 Text en © 2012 Broadhurst et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Broadhurst, Mara Jana
Ardeshir, Amir
Kanwar, Bittoo
Mirpuri, Julie
Gundra, Uma Mahesh
Leung, Jacqueline M.
Wiens, Kirsten E.
Vujkovic-Cvijin, Ivan
Kim, Charlie C.
Yarovinsky, Felix
Lerche, Nicholas W.
McCune, Joseph M.
Loke, P'ng
Therapeutic Helminth Infection of Macaques with Idiopathic Chronic Diarrhea Alters the Inflammatory Signature and Mucosal Microbiota of the Colon
title 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_short 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
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3499566/
https://www.ncbi.nlm.nih.gov/pubmed/23166490
http://dx.doi.org/10.1371/journal.ppat.1003000
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