ORIGINAL RESEARCH published: 06 July 2017 doi: 10.3389/fcimb.2017.00302

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients Guoqin Yu 1*, Javier Torres 2 , Nan Hu 3 , Rafael Medrano-Guzman 4 , Roberto Herrera-Goepfert 5 , Michael S. Humphrys 6 , Lemin Wang 3 , Chaoyu Wang 3 , Ti Ding 7 , Jacques Ravel 6 , Philip R. Taylor 3 , Christian C. Abnet 3 and Alisa M. Goldstein 8* 1

Integrative Tumor Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, 2 Unidad de Investigacion en Enfermedades Infecciosas, Unidad Medica de Alta Especialidad Pediatria, Centro Medico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico, 3 Metabolic Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States, 4 Unidad Medica de Alta Especialidad Oncología, Centro Medico Nacional SXXI, Instituto Mexicano del Seguro Social, Mexico City, Mexico, 5 Instituto Nacional de Cancerología, Secretaria de Salúd, Mexico City, Mexico, 6 Institute for Genome Sciences, University of Maryland School of Medicine, Baltimore, MD, United States, 7 Shanxi Cancer Hospital, Taiyuan, China, 8 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD, United States

Edited by: Lorenza Putignani, Bambino Gesù Ospedale Pediatrico (IRCCS), Italy Reviewed by: Jeong-Heon Cha, Yonsei University, South Korea Valerio Iebba, Sapienza Università di Roma, Italy *Correspondence: Guoqin Yu [email protected] Alisa M. Goldstein [email protected] Received: 15 March 2017 Accepted: 20 June 2017 Published: 06 July 2017 Citation: Yu G, Torres J, Hu N, Medrano-Guzman R, Herrera-Goepfert R, Humphrys MS, Wang L, Wang C, Ding T, Ravel J, Taylor PR, Abnet CC and Goldstein AM (2017) Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients. Front. Cell. Infect. Microbiol. 7:302. doi: 10.3389/fcimb.2017.00302

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especially at the time of gastric cancer diagnosis. Here we characterized the taxonomic and derived functional profiles of gastric microbiota in two different sets of gastric cancer patients, and compared them with microbial profiles in other body sites. Paired non-malignant and tumor tissues were sampled from 160 gastric cancer patients with 80 from China and 80 from Mexico. The 16S rRNA gene V3–V4 region was sequenced using MiSeq platform for taxonomic profiles. PICRUSt was used to predict functional profiles. Human Microbiome Project was used for comparison. We showed that Hp is the most abundant member of gastric microbiota in both Chinese and Mexican samples (51 and 24%, respectively), followed by oral-associated bacteria. Taxonomic (phylum-level) profiles of stomach microbiota resembled oral microbiota, especially when the Helicobacter reads were removed. The functional profiles of stomach microbiota, however, were distinct from those found in other body sites and had higher inter-subject dissimilarity. Gastric microbiota composition did not differ by Hp colonization status or stomach anatomic sites, but did differ between paired non-malignant and tumor tissues in either Chinese or Mexican samples. Our study showed that Hp is the dominant member of the non-malignant gastric tissue microbiota in many gastric cancer patients. Our results provide insights on the gastric microbiota composition and function in gastric cancer patients, which may have important clinical implications. Keywords: Helicobacter pylori, 16S rRNA, KEGG modules, microbiome, gastric cancer

Abbreviations: GC, Gastric Cancer; Hp, Helicobacter pylori; HMP, Human Microbiome Project; NCI, National Cancer Institute; OTUs, Operational Taxonomy Units; QIIME, Quantitative Insights into Microbial Ecology; PD_whole_tree, Phylogenetic diversity; PICRUSt, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States; PERMANOVA, Permutational Multivariate Analysis of Variance.

Frontiers in Cellular and Infection Microbiology | www.frontiersin.org

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July 2017 | Volume 7 | Article 302

Yu et al.

Stomach Microbiota of Gastric Cancer Patients

BACKGROUND

of the Shanxi Cancer Hospital and the National Cancer Institute (NCI). All subjects provided written informed consent prior to participation. Cases were histologically confirmed as adenocarcinomas by pathologists at both the Shanxi Cancer Hospital and the NCI. Clinical data was collected by review of medical records. Patients who were

Molecular Characterization of the Human Stomach Microbiota in Gastric Cancer Patients.

Helicobacter pylori (Hp) is the primary cause of gastric cancer but we know little of its relative abundance and other microbes in the stomach, especi...
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