Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>

ABSTRACT Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate tha...

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Autores principales: Chunxu Gao, Angela Major, David Rendon, Monica Lugo, Vanessa Jackson, Zhongcheng Shi, Yuko Mori-Akiyama, James Versalovic
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Publicado: American Society for Microbiology 2015
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spelling oai:doaj.org-article:eb3b3982c86c4934b19bccfa57f04b6e2021-11-15T15:41:24ZHistamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>10.1128/mBio.01358-152150-7511https://doaj.org/article/eb3b3982c86c4934b19bccfa57f04b6e2015-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01358-15https://doaj.org/toc/2150-7511ABSTRACT Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [18F]fluorodeoxyglucose ([18F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc+ L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon.IMPORTANCE Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc+ L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor-mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics.Chunxu GaoAngela MajorDavid RendonMonica LugoVanessa JacksonZhongcheng ShiYuko Mori-AkiyamaJames VersalovicAmerican Society for MicrobiologyarticleMicrobiologyQR1-502ENmBio, Vol 6, Iss 6 (2015)
institution DOAJ
collection DOAJ
language EN
topic Microbiology
QR1-502
spellingShingle Microbiology
QR1-502
Chunxu Gao
Angela Major
David Rendon
Monica Lugo
Vanessa Jackson
Zhongcheng Shi
Yuko Mori-Akiyama
James Versalovic
Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
description ABSTRACT Probiotics and commensal intestinal microbes suppress mammalian cytokine production and intestinal inflammation in various experimental model systems. Limited information exists regarding potential mechanisms of probiotic-mediated immunomodulation in vivo. In this report, we demonstrate that specific probiotic strains of Lactobacillus reuteri suppress intestinal inflammation in a trinitrobenzene sulfonic acid (TNBS)-induced mouse colitis model. Only strains that possess the hdc gene cluster, including the histidine decarboxylase and histidine-histamine antiporter genes, can suppress colitis and mucosal cytokine (interleukin-6 [IL-6] and IL-1β in the colon) gene expression. Suppression of acute colitis in mice was documented by diminished weight loss, colonic injury, serum amyloid A (SAA) protein concentrations, and reduced uptake of [18F]fluorodeoxyglucose ([18F]FDG) in the colon by positron emission tomography (PET). The ability of probiotic L. reuteri to suppress colitis depends on the presence of a bacterial histidine decarboxylase gene(s) in the intestinal microbiome, consumption of a histidine-containing diet, and signaling via the histamine H2 receptor (H2R). Collectively, luminal conversion of l-histidine to histamine by hdc+ L. reuteri activates H2R, and H2R signaling results in suppression of acute inflammation within the mouse colon.IMPORTANCE Probiotics are microorganisms that when administered in adequate amounts confer beneficial effects on the host. Supplementation with probiotic strains was shown to suppress intestinal inflammation in patients with inflammatory bowel disease and in rodent colitis models. However, the mechanisms of probiosis are not clear. Our current studies suggest that supplementation with hdc+ L. reuteri, which can convert l-histidine to histamine in the gut, resulted in suppression of colonic inflammation. These findings link luminal conversion of dietary components (amino acid metabolism) by gut microbes and probiotic-mediated suppression of colonic inflammation. The effective combination of diet, gut bacteria, and host receptor-mediated signaling may result in opportunities for therapeutic microbiology and provide clues for discovery and development of next-generation probiotics.
format article
author Chunxu Gao
Angela Major
David Rendon
Monica Lugo
Vanessa Jackson
Zhongcheng Shi
Yuko Mori-Akiyama
James Versalovic
author_facet Chunxu Gao
Angela Major
David Rendon
Monica Lugo
Vanessa Jackson
Zhongcheng Shi
Yuko Mori-Akiyama
James Versalovic
author_sort Chunxu Gao
title Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
title_short Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
title_full Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
title_fullStr Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
title_full_unstemmed Histamine H2 Receptor-Mediated Suppression of Intestinal Inflammation by Probiotic <named-content content-type="genus-species">Lactobacillus reuteri</named-content>
title_sort histamine h2 receptor-mediated suppression of intestinal inflammation by probiotic <named-content content-type="genus-species">lactobacillus reuteri</named-content>
publisher American Society for Microbiology
publishDate 2015
url https://doaj.org/article/eb3b3982c86c4934b19bccfa57f04b6e
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