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      The Gastric Microbiome Is Perturbed in Advanced Gastric Adenocarcinoma Identified Through Shotgun Metagenomics

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          Abstract

          Objective: Dysbiosis of gastric microbiota such as Helicobacter pylori plays a significant role in pathogenesis and progression of gastric cancer. Our aim was to evaluate the composition and functional effects of gastric microbiota in superficial gastritis (SG) and advanced gastric adenocarcinoma (GC).

          Methods: We carried out shotgun metagenomic sequencing on gastric wash samples from 6 patients with GC and 5 patients with SG. The taxonomic composition was profiled using MetaPhlAn2 and functional gene pathway was profiled using HUMAnN2. Differences in microbial composition and pathways between the two patient groups were assessed via LEfSe.

          Results: The gastric microbiota in GC patients was characterized by reduced species richness, enrichment of 13 bacterial taxa and depletion of 31 taxa ( q < 0.05). The most representative taxa which were abundant in GC corresponded to the commensals or opportunistic pathogens that usually colonize the oral cavity, including genera Neisseria, Alloprevotella, and Aggregatibacter, species Streptococcus_mitis_oralis_pneumoniae and strain Porphyromonas_endodontalis.t_GCF_000174815. Each of the three GC-associated genera could separate GC from SG completely. In particular, Sphingobium yanoikuyae, a bacterium capable of degrading carcinogenic compounds, was depleted in GC. Functionally, pathways associated with the biosynthesis of lipopolysaccharide (LPS) and L-arginine were enriched in GC, whereas pathways involved in the fermentation of short chain fatty acids (SCFAs) and branched amino acid metabolism were more abundant in SG.

          Conclusions: Our results present new alterations in the gastric microbiome in patients with GC from a whole-genome perspective, suggesting that microbiome composition and function can be used for prognosis and diagnosis of GC.

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          Most cited references35

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          Pathobiology of Helicobacter pylori-Induced Gastric Cancer.

          Colonization of the human stomach by Helicobacter pylori and its role in causing gastric cancer is one of the richest examples of a complex relationship among human cells, microbes, and their environment. It is also a puzzle of enormous medical importance given the incidence and lethality of gastric cancer worldwide. We review recent findings that have changed how we view these relationships and affected the direction of gastric cancer research. For example, recent data have indicated that subtle mismatches between host and microbe genetic traits greatly affect the risk of gastric cancer. The ability of H pylori and its oncoprotein CagA to reprogram epithelial cells and activate properties of stemness show the sophisticated relationship between H pylori and progenitor cells in the gastric mucosa. The observation that cell-associated H pylori can colonize the gastric glands and directly affect precursor and stem cells supports these observations. The ability to mimic these interactions in human gastric organoid cultures as well as animal models will allow investigators to more fully unravel the extent of H pylori control on the renewing gastric epithelium. Finally, our realization that external environmental factors, such as dietary components and essential micronutrients, as well as the gastrointestinal microbiota, can change the balance between H pylori's activity as a commensal or a pathogen has provided direction to studies aimed at defining the full carcinogenic potential of this organism.
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            The MetaCyc database of metabolic pathways and enzymes

            Abstract MetaCyc (https://MetaCyc.org) is a comprehensive reference database of metabolic pathways and enzymes from all domains of life. It contains more than 2570 pathways derived from >54 000 publications, making it the largest curated collection of metabolic pathways. The data in MetaCyc is strictly evidence-based and richly curated, resulting in an encyclopedic reference tool for metabolism. MetaCyc is also used as a knowledge base for generating thousands of organism-specific Pathway/Genome Databases (PGDBs), which are available in the BioCyc (https://BioCyc.org) and other PGDB collections. This article provides an update on the developments in MetaCyc during the past two years, including the expansion of data and addition of new features.
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              Toll-like receptors and cancer.

              Toll-like receptors (TLRs) are a family of pattern recognition receptors that are best-known for their role in host defence from infection. Emerging evidence also suggests that TLRs have an important role in maintaining tissue homeostasis by regulating the inflammatory and tissue repair responses to injury. The development of cancer has been associated with microbial infection, injury, inflammation and tissue repair. Here we discuss how the function of TLRs may relate to these processes in the context of carcinogenesis.
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                Author and article information

                Contributors
                Journal
                Front Cell Infect Microbiol
                Front Cell Infect Microbiol
                Front. Cell. Infect. Microbiol.
                Frontiers in Cellular and Infection Microbiology
                Frontiers Media S.A.
                2235-2988
                12 December 2018
                2018
                : 8
                : 433
                Affiliations
                [1] 1Graduate School, Third Military Medical University (Army Medical University) , Chongqing, China
                [2] 2Department of General Surgery, Navy General Hospital , Beijing, China
                Author notes

                Edited by: Jorge Frias-Lopez, University of Florida, United States

                Reviewed by: Amedeo Amedei, Università degli Studi di Firenze, Italy; Guo-Bao Tian, Sun Yat-sen University, China

                *Correspondence: Chao-Jun Zhang doctorzhangxq@ 123456aliyun.com

                This article was submitted to Microbiome in Health and Disease, a section of the journal Frontiers in Cellular and Infection Microbiology

                Article
                10.3389/fcimb.2018.00433
                6299874
                30619779
                52702efe-fd9a-4a60-9410-d3083e14742e
                Copyright © 2018 Hu, Pang, Huang, Zhang and Zhang.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 14 September 2018
                : 30 November 2018
                Page count
                Figures: 3, Tables: 1, Equations: 0, References: 68, Pages: 11, Words: 7734
                Categories
                Cellular and Infection Microbiology
                Original Research

                Infectious disease & Microbiology
                gastric adenocarcinoma,shotgun metagenomics,microbiome,inflammation,human

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