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

Guoqin Yu,Alisa M Goldstein,Philip R Taylor,Chaoyu Wang,Roberto Herrera-Goepfert,Javier Torres,Jacques Ravel,Rafael Medrano-Guzman,Ti Ding,Christian C Abnet,Michael S Humphrys,Nan Hu,Lemin Wang

doi:10.3389/fcimb.2017.00302

Abstract

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.

Highlights

Gastric cancer (GC) is the fifth most common cancer in the world and the third leading cause of cancer death (Ferlay et al, 2013)
We showed that Helicobacter pylori (Hp) is the most abundant member of the stomach microbiota, followed by the genera that are commonly seen in the oral microbiota
The principal coordinates plots based on functional profiles, suggested that stomach microbiota was distinct from the microbiota of other body sites, and had higher intersubject dissimilarity

Summary

Introduction

Gastric cancer (GC) is the fifth most common cancer in the world and the third leading cause of cancer death (Ferlay et al, 2013). GC incidence varies widely with high rates in Asia, Eastern Europe, and Central and South America, and low rates in North America and Africa (Carneiro, 2014). GC may arise in cardia or in non-cardia (the fundus, body, or pylorus section). Chronic colonization of Helicobacter pylori (Hp) is known to increase the risk of non-cardia cancer (Cavaleiro-Pinto et al, 2011). The association between Hp colonization and gastric cardia cancer varies by populations. The studies in Western countries tend to show a neutral or even negative association while in Eastern populations namely China, Japan, and Korea, there is strong evidence of a higher risk of cardia cancer among subjects with Hp colonization (Cavaleiro-Pinto et al, 2011)

Methods

Results

Conclusion