Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype

ABSTRACT Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk....

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Autores principales:	Jennifer M. Noto, Joseph P. Zackular, Matthew G. Varga, Alberto Delgado, Judith Romero-Gallo, Matthew B. Scholz, M. Blanca Piazuelo, Eric P. Skaar, Richard M. Peek
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	CagA Helicobacter pylori gastric cancer gastric microbiota iron deficiency Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/4e1d7e064e0343d7a2ef53ea353bd1c7
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spelling	oai:doaj.org-article:4e1d7e064e0343d7a2ef53ea353bd1c72021-11-15T15:55:23ZModification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype10.1128/mBio.00955-192150-7511https://doaj.org/article/4e1d7e064e0343d7a2ef53ea353bd1c72019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00955-19https://doaj.org/toc/2150-7511ABSTRACT Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+ H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease. IMPORTANCE Microbial communities are essential for the maintenance of human health, and when these communities are altered, hosts can become susceptible to inflammation and disease. Dysbiosis contributes to gastrointestinal cancers, and specific bacterial species are associated with this phenotype. This study uses a robust and reproducible animal model to demonstrate that H. pylori infection induces gastric dysbiosis in a cagA-dependent manner and further that dysbiosis and altered microbial community structure parallel the severity of H. pylori-induced gastric injury. Ultimately, such models of H. pylori infection and cancer that can effectively evaluate multiple determinants simultaneously may yield effective strategies for manipulating the gastric microbiota to prevent the development of gastric cancer.Jennifer M. NotoJoseph P. ZackularMatthew G. VargaAlberto DelgadoJudith Romero-GalloMatthew B. ScholzM. Blanca PiazueloEric P. SkaarRichard M. PeekAmerican Society for MicrobiologyarticleCagAHelicobacter pylorigastric cancergastric microbiotairon deficiencyMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	CagA Helicobacter pylori gastric cancer gastric microbiota iron deficiency Microbiology QR1-502
spellingShingle	CagA Helicobacter pylori gastric cancer gastric microbiota iron deficiency Microbiology QR1-502 Jennifer M. Noto Joseph P. Zackular Matthew G. Varga Alberto Delgado Judith Romero-Gallo Matthew B. Scholz M. Blanca Piazuelo Eric P. Skaar Richard M. Peek Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
description	ABSTRACT Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+ H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease. IMPORTANCE Microbial communities are essential for the maintenance of human health, and when these communities are altered, hosts can become susceptible to inflammation and disease. Dysbiosis contributes to gastrointestinal cancers, and specific bacterial species are associated with this phenotype. This study uses a robust and reproducible animal model to demonstrate that H. pylori infection induces gastric dysbiosis in a cagA-dependent manner and further that dysbiosis and altered microbial community structure parallel the severity of H. pylori-induced gastric injury. Ultimately, such models of H. pylori infection and cancer that can effectively evaluate multiple determinants simultaneously may yield effective strategies for manipulating the gastric microbiota to prevent the development of gastric cancer.
format	article
author	Jennifer M. Noto Joseph P. Zackular Matthew G. Varga Alberto Delgado Judith Romero-Gallo Matthew B. Scholz M. Blanca Piazuelo Eric P. Skaar Richard M. Peek
author_facet	Jennifer M. Noto Joseph P. Zackular Matthew G. Varga Alberto Delgado Judith Romero-Gallo Matthew B. Scholz M. Blanca Piazuelo Eric P. Skaar Richard M. Peek
author_sort	Jennifer M. Noto
title	Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
title_short	Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
title_full	Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
title_fullStr	Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
title_full_unstemmed	Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype
title_sort	modification of the gastric mucosal microbiota by a strain-specific <named-content content-type="genus-species">helicobacter pylori</named-content> oncoprotein and carcinogenic histologic phenotype
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/4e1d7e064e0343d7a2ef53ea353bd1c7
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Modification of the Gastric Mucosal Microbiota by a Strain-Specific <named-content content-type="genus-species">Helicobacter pylori</named-content> Oncoprotein and Carcinogenic Histologic Phenotype

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