Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Sep 7, 2021; 27(33): 5575-5594
Published online Sep 7, 2021. doi: 10.3748/wjg.v27.i33.5575
Characterization of gut microbiome and metabolome in Helicobacter pylori patients in an underprivileged community in the United States
Brian White, John D Sterrett, Zoya Grigoryan, Lauren Lally, Jared D Heinze, Hyder Alikhan, Christopher A Lowry, Lark J Perez, Joshua DeSipio, Sangita Phadtare
Brian White, Sangita Phadtare, Department of Biomedical Sciences, Cooper Medical School of Rowan University, Camden, NJ 08103, United States
John D Sterrett, Jared D Heinze, Christopher A Lowry, Department of Integrative Physiology, University of Colorado Boulder, Boulder, CO 80309, United States
Zoya Grigoryan, Department of Internal Medicine, Lenox Hill Hospital, NYC, NY 10075, United States
Lauren Lally, Department of Internal Medicine, Thomas Jefferson University Hospital, Philadelphia, PA 19107, United States
Hyder Alikhan, Department of Biological Sciences, Rowan University, Glassboro, NJ 08028, United States
Lark J Perez, Department of Chemistry and Biochemistry, Rowan University, Glassboro, NJ 08028, United States
Joshua DeSipio, Department of Gastroenterology, Cooper University Hospital, Camden, NJ 08103, United States
Author contributions: White B, Sterrett JD and Grigoryan Z contributed equally to the work; DeSipio J, and Phadtare S designed and coordinated the study; Grigoryan Z and Lally L collected patient samples and data; Phadtare S performed the sample processing for 16S rRNA gene sequencing; Heinze JD provided guidance for sample processing methodology; Grigoryan Z and Phadtare S performed the 16S rRNA sequencing data analysis; Sterrett JD and Lowry CA created the analysis codes essential for analysis and provided guidance for data analysis; Alikhan H and Perez LJ performed the fatty acid analysis; Lally L and White B carried out literature search; White B, Sterrett JD, Lowry CA, Perez LJ, DeSipio J and Phadtare S interpreted the analyzed data and wrote the final draft of the manuscript; all authors approved the final version of the article.
Supported by The Camden Health Research Initiative grant to Sangita Phadtare.
Institutional review board statement: This study received approval by the Cooper Health System Institutional Review Board (IRB) (17-077EX) and all the steps were carried out as per the standards set by the IRB.
Institutional animal care and use committee statement: There are no animals used in the study.
Conflict-of-interest statement: The authors report no conflicts of interest.
Data sharing statement: The code is available at https://github.com/sterrettJD/H-pylori-microbiome-analysis. Volcano plot data are included as Supplementary Tables 1-3(Supplementary Table 1: Volcano plot data with all Helicobacter data set; Supplementary Table 2: Volcano plot data with High Bacteroidetes; Supplementary Table 3: Volcano plot data with High Firmicutes).
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Sangita Phadtare, BSc, MSc, PhD, Professor, Department of Biomedical Sciences, Cooper Medical School of Rowan University, 401 S Broadway, Camden, NJ 08103, United States. phadtare@rowan.edu
Received: March 31, 2021
Peer-review started: March 31, 2021
First decision: June 23, 2021
Revised: July 2, 2021
Accepted: August 13, 2021
Article in press: August 13, 2021
Published online: September 7, 2021
Processing time: 155 Days and 15.9 Hours
ARTICLE HIGHLIGHTS
Research background

Helicobacter pylori (H. pylori), a bacterium that infects approximately half of the world’s population, is associated with various gastrointestinal diseases, including peptic ulcers, non-ulcer dyspepsia, gastric adenocarcinoma, and gastric lymphoma. Following the global trend in emerging antibiotic resistance, rates of clarithromycin, metronidazole, and levofloxacin resistance among H. pylori strains have increased markedly, causing high rates of eradication failure.

Research motivation

As the burden of antibiotic resistance increases, the need for new adjunct therapies designed to facilitate H. pylori eradication and reduce negative distal outcomes associated with infection has become more pressing. Characterization of the interactions between H. pylori, the fecal microbiome, and fecal fatty acid metabolism, as well as the mechanisms underlying these interactions, may offer new therapeutic approaches.

Research objectives

The aim of this study is to characterize the fecal microbiome and metabolome in H. pylori patients in a socioeconomically challenged and underprivileged inner-city community.

Research methods

Stool samples from 19 H. pylori patients and 16 control subjects were analyzed. 16S rRNA gene sequencing was performed on normalized pooled amplicons using the Illumina MiSeq System using a MiSeq reagent kit v2. Alpha and beta diversity analyses were performed in QIIME 2. Non-targeted fatty acid analysis of the samples was carried out using gas chromatography-mass spectrometry, which measures the total content of 30 fatty acids in stool after conversion into their corresponding fatty acid methyl esters. Multi-dimensional scaling (MDS) was performed on Bray-Curtis distance matrices created from both the metabolomics and microbiome datasets and a Procrustes test was performed on the metabolomics and microbiome MDS coordinates.

Research results

Fecal microbiome analysis showed that alpha diversity was lowest in H. pylori patients over 40 years of age compared to control subjects of similar age group. Beta diversity analysis of the samples revealed significant differences in microbial community structure between H. pylori patients and control subjects across all ages. Thirty-eight and six taxa were identified by Linear Discriminant Analysis (LDA) using LDA Effect Size to be enriched in H. pylori patients vs control individuals, respectively. Taxa that were enriched in H. pylori patients included Atopobium, Gemellaceae, Micrococcaceae, Gemellales and Rothia (R. mucilaginosa). Notably, relative abundance of the phylum Verrucomicrobia was decreased in H. pylori patients compared to control subjects. Procrustes analysis showed a significant relationship between the microbiome and metabolome datasets. Stool samples from H. pylori patients showed increases in several fatty acids including the polyunsaturated fatty acids (PUFAs) 22:4n6, 22:5n3, 20:3n6 and 22:2n6, while decreases were noted in other fatty acids including the PUFA 18:3n6. The pattern of changes in fatty acid concentration correlated to the Bacteroidetes:Firmicutes ratio determined by 16S rRNA gene analysis.

Research conclusions

The study suggests H. pylori-associated changes to the fecal microbiome and fecal fatty acid metabolism. Such changes may have implications for improving eradication rates and minimizing associated negative distal outcomes.

Research perspectives

Future study with greater power should be directed to confirming the distal gut dysbiosis and changes to fecal fatty acid metabolism seen in our exploratory analysis of patients with H. pylori infection, as well as towards exploring the relationships between such phenomena and eradication success, colorectal cancer, and metabolic disease.