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World J Gastroenterol. Oct 7, 2021; 27(37): 6224-6230
Published online Oct 7, 2021. doi: 10.3748/wjg.v27.i37.6224
Impact of Helicobacter pylori infection on gut microbiota
Chikara Iino, Tadashi Shimoyama
Chikara Iino, Tadashi Shimoyama, Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
Tadashi Shimoyama, Department of Internal Medicine, Aomori General Health Examination Center, Aomori 030-0962, Japan
ORCID number: Chikara Iino (0000-0001-6844-4415); Tadashi Shimoyama (0000-0001-9615-0000).
Author contributions: Iino C and Shimoyama T designed the review; Iino C interpreted the data and drafted the manuscript; Shimoyama T critically revised the paper.
Conflict-of-interest statement: The authors declare that there are no conflicts of interest regarding the publication of this paper.
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: Tadashi Shimoyama, FACG, MD, PhD, Director, Department of Internal Medicine, Aomori General Health Examination Center, 2-19-12 Tsukuda, Aomori 030-0962, Japan. tsimo@hirosaki-u.ac.jp
Received: March 16, 2021
Peer-review started: March 16, 2021
First decision: April 29, 2021
Revised: May 13, 2021
Accepted: September 2, 2021
Article in press: September 2, 2021
Published online: October 7, 2021

Abstract

A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.

Key Words: Helicobacter pylori, Gut microbiota, Atrophic gastritis, Eradication, Proton pump inhibitor

Core Tip: Helicobacter pylori (H. pylori) eradication alters gut microbiota within a short period after eradication; this is attributed to antibiotics and proton pump inhibitors. However, most of these alterations reverse back to baseline levels over a long period of time. Modification of acidity in the stomach with mucosal atrophy caused by H. pylori infection alters the gut microbiota. As the human gut microbiome is diverse among individuals, a large population size is needed to study. Adjustment of biases associated with the composition of the gut microbiota is also crucial for accurate evaluation of the association between H. pylori infection and the gut microbiota.



INTRODUCTION

In recent years, a number of studies related to gut microbiota have been published, shedding light on the association between gut microbiota and human health. The human microbiota consists of as many as 10-100 trillion symbiotic microbial cells harbored in the intestinal tract of every person[1]. The gut microbiota plays a pivotal role of in the metabolic, physiological, and immunological systems of the human body[2], and its structure is closely associated with an individual’s health and past illnesses[3].

Accordingly, research on the association between Helicobacter pylori (H. pylori) infection and the microbiota has also increased[4]. Most of the studies, including our previous studies that revealed the influence of H. pylori infection on the gut microbiota, have focused on the gastric microbiota, while only a few studies have investigated the gut microbiota harbored in the intestinal tract of patients with H. pylori infection[5,6]. Subsequently, some published studies have revealed new findings and have improved our understanding of this phenomenon. Therefore, the current review aims to summarize the recent evidence on the influence of H. pylori infection on the gut microbiota, while focusing on the gut microbiota in the intestinal tract, and to discuss the mechanisms underlying the H. pylori mediated alterations in the gut microbiota.

H. PYLORI AND GUT MICROBIOTA

More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy on the gut microbiota[7-11] (Table 1). Two earlier studies were based on in situ hybridization and bacterial culturing using fecal samples. A study showed that the gut microbiota of H. pylori-positive patients was characterized by an increase in the growth of acid-tolerant Lactobacillus acidophilus[7]. Another study found that the total amount of Anaerobes and Clostridia present in H. pylori-positive patients was significantly lower as compared to that of H. pylori-negative subjects[8]. Subsequent studies were based on the analysis of the fecal 16S rRNA. The analysis of the fecal 16S rRNA from 70 H. pylori-positive subjects and 35 H. pylori-negative subjects showed a decrease in the abundance of Clostridia as well as total anaerobes in the fecal samples of H. pylori-positive individuals[9]. In a study on young adults, the microbial diversity of the gut microbiota was higher in patients infected with H. pylori than in healthy controls. Moreover, at the phylum level, the relative abundance of Proteobacteria significantly increased in patients infected with H. pylori[10]. In contrast, only the study by Martín-Núñez et al[11] revealed that in comparison with uninfected individuals, the alpha diversity of gut microbiota was significantly lower in patients infected with H. pylori. In these studies, the composition of the gut microbiota between subjects infected and uninfected was not the primary endpoint. Moreover, the number of subjects taken into consideration was relatively small. As the diversity of the human gut microbiome varies among individuals, a large population size is needed.

Table 1 Studies for the influence of Helicobacter pylori infection on gut microbiota.
Ref.
Study groups H. pylori (+) vs (-)
Aim
Main findings for H. pylori positive subject
Bühling et al[7], 200151 vs 27Sub analysis for eradication studyL. acidophilus
Myllyluoma et al[8], 200739 vs 19Sub analysis for eradication studyClostridia ↓, Anaerobes
Chen et al[9], 201870 vs 35Sub analysis for eradication studyDiversity ↑, Nitrospirae ↓, the relative abundance of 19 pathways were significantly different between H. pylori-negative and H. pylori-positive patients
Iino et al[5], 2018226 vs 524Analysis of microbiota without eradicationLactobacillus
He et al[10], 201910 vs 7Sub analysis for eradication studyDiversity ↑, Proteobacteria
Iino et al[6], 2020214 vs 214Analysis of microbiota without eradicationDiversity ↑, Haemophilusu ↑, Streptococcus ↑, Gemella ↑, Actinomyces
Martín-Núñez et al[11], 201940 vs 20Sub analysis for eradication studyDiversity ↓, Oscillospira
Dash et al[12], 201912 vs 48Analysis of microbiota without eradicationDiversity ↑, Succinivibrio ↑, Coriobacteriaceae ↑, Enterococcaceae ↑, Rikenellaceae ↑, Candida glabrata
Frost et al[13], 2019212 vs 212Analysis of microbiota without eradicationDiversity ↑, Prevotella ↑, Bacteroidetes ↓, Parasutterella ↑, Holdemanella ↑, Betaproteobacteria ↑, Pseudoflavonifractor ↓, Alisonella ↑, Howardella

A few studies have been conducted to investigate the influence of H. pylori infection on the gut microbiota[5,6,12,13]. Our large population study performed using 16S rRNA amplification from fecal samples revealed that Lactobacillus in the human gut microbiota may be influenced by H. pylori infection[5]. In a small-sample study, Dash et al[12] showed that the gut microbiota of H. pylori-infected individuals were enriched with members of Succinivibrio, Coriobacteriaceae, Enterococcaceae, and Rikenellaceae families. Furthermore, several studies have suggested that the composition of the human gut microbiota changes with age, body mass index (BMI), and sex[14-16]. Therefore, we excluded the influence of these factors using the propensity score matching, which has not been considered in previous studies. We compared 214 H. pylori-positive subjects and 214 matched H. pylori-negative subjects from a large population study and found a higher gut microbial diversity and a different gut microbiota composition in subjects with H. pylori[6]. Furthermore, at the genus level, the abundance of Actinomyces, Gemella, Streptococcus, and Haemophilus was significantly higher in the gut microbiota of H. pylori-infected subjects. Another recent study conducted by Frost et al[13] assessed the microbiota composition of 212 H. pylori-positive subjects and 212 matched negative controls. Similar to our study, all control samples were matched with respect to age, sex, BMI, alcohol consumption, smoking, proton pump inhibitor (PPI) usage, history of peptic ulcer disease, and dietary habits. This study demonstrated that H. pylori infection was associated with alterations in fecal microbiota and an overall increase in fecal microbial diversity. A later study on the long-term effects of H. pylori eradication demonstrated that the structure of the gut microbiota is more closely associated with subject-specific parameters, such as age or BMI, than with the eradication therapy itself[17]. Therefore, adjusting for biases associated with the composition of the gut microbiota is crucial for accurate evaluation of its composition. Diet is a key modifiable factor affecting the composition of the gut microbiota[18]. However, only one study has addressed this parameter[13].

THE INFLUENCE OF H. PYLORI ERADICATION ON GUT MICROBIOTA

A number of published studies have investigated the changes in the gut microbiota after H. pylori eradication. A recent systematic review of 24 articles examining the effect of H. pylori eradication on the gut microbiota revealed that most studies identified a significant decrease in the alpha diversity of the gut microbiota within a short period after eradication but no further alterations were observed for over 6 mo after H. pylori eradication[19]. Additionally, the abundance of Proteobacteria increased during a short-term follow-up whereas that of Lactobacillus decreased; Enterobacteriaceae and Enterococcus increased during the short-term and interim follow-up. Moreover, a more recent study evaluating the long-term effects of H. pylori eradication found out that the composition of the gut microbiota was restored to baseline status over the 2 years after eradication, and the relative abundances of the microbial species at the genus level before and after eradication did not differ significantly[17]. However, modest differences in the taxonomic composition were observed before and after eradication. The findings of this study where diversity of the microbiota tends to decrease in the short period after eradication and returns to baseline thereafter, it was consistent with the findings of most studies[9,10,20-26]. However, the taxonomic composition before and after eradication varied among the studies[21,22]. Some studies demonstrated that the relative abundance of all genera was restored to baseline levels. Other studies revealed notable changes at the genus level[10,24-26]. Thus, it may be assumed that after the microbial diversity returns to baseline, the levels of each strain might demonstrate minor variations following the eradication of H. pylori.

THE MECHANISMS UNDERLYING H. PYLORI INFECTION INDUCED GUT MICROBIOTA

Although the mechanisms underlying H. pylori infection associated alterations in gut microbiota are still unknown, some studies have suggested possible contributing factors; these included host immune responses, virulence factors, physical contact and modification of gastric acidity[4,27]. A previous study performed using a transgenic Drosophila model revealed that the virulence factor, cytotoxin-associated gene A (CagA), of H. pylori may contribute to gut microbiota dysbiosis[28]. CagA, which is translocated into host epithelial cells after bacterial attachment, impairs cell polarity and affects host signaling pathways, thereby promoting inflammation[29]. Vacuolating cytotoxin A (VacA) is also an important virulence factor of H. pylori. VacA is a secreted toxin that lead to damages of gastric epithelial cells, and promotes cell death[30]. CagA and VacA counter-regulate each other to manipulate host cell responses[31]. CagA and VacA can alter the gastric microbiota and immune phenotypes previously attributed to H. pylori infection in the stomach[28]. Therefore, CagA and VacA have been associated with important requirements for long-term sequelae in humans. As such, ongoing crosstalk between H. pylori and gastric commensal microbiota may affect the host immune response. The altered host immune response may also modulate the gut microbiota[9,32]. A previous review suggested the possibility of a direct interaction of H. pylori, which migrates from the stomach towards the intestinal tract, with the local gut microbiota[4]. However, this hypothesis is yet to be proven. In fact, in our previous study, the presence of H. pylori in the intestinal tract was found to be rare even in subjects with H. pylori infection[6]. Therefore, the influence of H. pylori in the intestine on gut microbiota seems to be limited.

Modification of gastric acidity as a result of H. pylori infection is one of the variable effects on altered gut microbiota. PPIs, which decrease gastric acidity, affect the gut microbiota[33,34]. Reduced gastric acid promotes the passage of acid-sensitive bacteria and changes the intestinal environment[35]. Similar to the interference with the action of PPIs, H. pylori can regulate gastric luminal acidity. H. pylori infection is generally acquired during childhood and persists for life unless eradicated by treatment. In the initial stages of H. pylori infection, acute gastritis temporarily leads to impaired gastric acid secretion[36]. In later stages, a significant decrease in gastric acid secretion is observed in individuals who develop severe atrophic gastritis[36,37]. Previous studies investigating the gut microbiota following PPI administration detected an increase in the Lactobacillus population in the gut microbiota[33,34]. We evaluated Lactobacillus according to the degree of gastric atrophy in subjects with and without H. pylori infection[5]. The relative abundance of Lactobacillus in the human gut microbiota significantly increased after the development of severe atrophic gastritis. In another study, after adjusting for biases, we demonstrated that among H. pylori-infected subjects, a significant increase in the abundance of the genus Streptococcus was observed in subjects with severe atrophic gastritis[6]. These results support the hypothesis that severe atrophic gastritis reduces gastric acid secretion and affects the composition of the gut microbiota, similar to the results of PPI administration. Most previous studies examining the association between H. pylori infection and gut microbiota have not considered the influence of gastric mucosal atrophy. However, atrophic gastritis may be an important mechanism associated with the changes in the gut microbiota induced by H. pylori infection.

In previous studies, although H. pylori eradication was observed to alter gut microbiota within a short period, most of the changes induced tended to return to baseline levels over a long periods after eradication therapy[9,10,20-26]. The changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and PPIs that were administered for H. pylori eradication. This finding was represented by a study that demonstrated a decrease in gut microbial diversity within a short period after eradication therapy in both patients with and without successful eradication[38]. The changes in the diversity within a short period after eradication may be attributed to the eradication therapy itself. Hence, the influence of eradication therapy on the gut microbiota would diminish over a long period of time. After eradication, the influence of host immune responses towards H. pylori, virulence factors, and physical contact with H. pylori could decrease or disappear. In contrast, the modification of gastric acidity depends on the degree of mucosal atrophy. Hence, after H. pylori eradication, gastric acid secretion gradually improves in patients without gastric mucosal atrophy[39]. However, this improvement is not observed in patients with severe atrophic gastritis[40]. Further studies demonstrating minor changes in the gut microbiota over a long period need to be conducted using a large number of subjects with severe atrophic gastritis. Especially after H. pylori eradication, mechanisms other than gastric acid modification would not have a significant impact on the gut microbiota.

CONCLUSION

Although all the studies demonstrated a compositional change in the gut microbiota of H. pylori-infected patients, the results of these studies were not consistent with each other. This incompatibility may be attributed to several factors. Although remarkable variations are observed in the gut microbiota among individuals, the sample size considered in these studies was relatively small, and subjects were included regardless of biases associated with the composition of the gut microbiota, such as, age, gender, BMI and diet. Therefore, an analysis of gut microbiota in a large population should be conducted while adjusting to considerable biases. Particularly, it is necessary to evaluate of the degree of atrophic gastritis, which is associated with gastric acid production, when investigating the influence of H. pylori infection on the gut microbiota. Additionally, the virulence of H. pylori differs depending on the status of CagA. The prevalence of CagA-positive H. pylori infection varies, and the prevalence of the most virulent strain, eliciting the East Asian-type CagA phenotype, is dependent on geographical area[41]. Therefore, the investigation of the influence of H. pylori infection on the gut microbiota may yield different results depending on the area in which the study is conducted. Future studies should consider these points and predict the mechanisms underlying H. pylori infection induced changes in the gut microbiota.

Footnotes

Manuscript source: Invited manuscript

Corresponding Author's Membership in Professional Societies: American College of Gastroenterology; American Gastroenterological Association; The Japanese Society of Gastroenterology.

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: Japan

Peer-review report’s scientific quality classification

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P-Reviewer: Dong XS S-Editor: Gao CC L-Editor: A P-Editor: Yuan YY

References
1.  Ursell LK, Metcalf JL, Parfrey LW, Knight R. Defining the human microbiome. Nutr Rev. 2012;70 Suppl 1:S38-S44.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 375]  [Cited by in F6Publishing: 273]  [Article Influence: 41.7]  [Reference Citation Analysis (0)]
2.  Jandhyala SM, Talukdar R, Subramanyam C, Vuyyuru H, Sasikala M, Nageshwar Reddy D. Role of the normal gut microbiota. World J Gastroenterol. 2015;21:8787-8803.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 755]  [Cited by in F6Publishing: 595]  [Article Influence: 151.0]  [Reference Citation Analysis (3)]
3.  Gerritsen J, Smidt H, Rijkers GT, de Vos WM. Intestinal microbiota in human health and disease: the impact of probiotics. Genes Nutr. 2011;6:209-240.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 405]  [Cited by in F6Publishing: 314]  [Article Influence: 40.5]  [Reference Citation Analysis (0)]
4.  Tao ZH, Han JX, Fang JY. Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota. Helicobacter. 2020;25:e12754.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
5.  Iino C, Shimoyama T, Chinda D, Arai T, Chiba D, Nakaji S, Fukuda S. Infection of Helicobacter pylori and Atrophic Gastritis Influence Lactobacillus in Gut Microbiota in a Japanese Population. Front Immunol. 2018;9:712.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 12]  [Cited by in F6Publishing: 12]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
6.  Iino C, Shimoyama T, Chinda D, Sakuraba H, Fukuda S, Nakaji S. Influence of Helicobacter pylori Infection and Atrophic Gastritis on the Gut Microbiota in a Japanese Population. Digestion. 2020;101:422-432.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 3.0]  [Reference Citation Analysis (0)]
7.  Bühling A, Radun D, Müller WA, Malfertheiner P. Influence of anti-Helicobacter triple-therapy with metronidazole, omeprazole and clarithromycin on intestinal microflora. Aliment Pharmacol Ther. 2001;15:1445-1452.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 52]  [Cited by in F6Publishing: 49]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
8.  Myllyluoma E, Ahlroos T, Veijola L, Rautelin H, Tynkkynen S, Korpela R. Effects of anti-Helicobacter pylori treatment and probiotic supplementation on intestinal microbiota. Int J Antimicrob Agents. 2007;29:66-72.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 57]  [Cited by in F6Publishing: 44]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
9.  Chen L, Xu W, Lee A, He J, Huang B, Zheng W, Su T, Lai S, Long Y, Chu H, Chen Y, Wang L, Wang K, Si J, Chen S. The impact of Helicobacter pylori infection, eradication therapy and probiotic supplementation on gut microenvironment homeostasis: An open-label, randomized clinical trial. EBioMedicine. 2018;35:87-96.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 44]  [Cited by in F6Publishing: 41]  [Article Influence: 14.7]  [Reference Citation Analysis (0)]
10.  He C, Peng C, Wang H, Ouyang Y, Zhu Z, Shu X, Zhu Y, Lu N. The eradication of Helicobacter pylori restores rather than disturbs the gastrointestinal microbiota in asymptomatic young adults. Helicobacter. 2019;24:e12590.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 20]  [Cited by in F6Publishing: 20]  [Article Influence: 10.0]  [Reference Citation Analysis (0)]
11.  Martín-Núñez GM, Cornejo-Pareja I, Coin-Aragüez L, Roca-Rodríguez MDM, Muñoz-Garach A, Clemente-Postigo M, Cardona F, Moreno-Indias I, Tinahones FJ. H. pylori eradication with antibiotic treatment causes changes in glucose homeostasis related to modifications in the gut microbiota. PLoS One. 2019;14:e0213548.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 16]  [Cited by in F6Publishing: 12]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
12.  Dash NR, Khoder G, Nada AM, Al Bataineh MT. Exploring the impact of Helicobacter pylori on gut microbiome composition. PLoS One. 2019;14:e0218274.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 28]  [Article Influence: 15.0]  [Reference Citation Analysis (0)]
13.  Frost F, Kacprowski T, Rühlemann M, Bang C, Franke A, Zimmermann K, Nauck M, Völker U, Völzke H, Biffar R, Schulz C, Mayerle J, Weiss FU, Homuth G, Lerch MM. Helicobacter pylori infection associates with fecal microbiota composition and diversity. Sci Rep. 2019;9:20100.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 17]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
14.  Hasan N, Yang H. Factors affecting the composition of the gut microbiota, and its modulation. PeerJ. 2019;7:e7502.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 95]  [Cited by in F6Publishing: 69]  [Article Influence: 47.5]  [Reference Citation Analysis (0)]
15.  Borgo F, Garbossa S, Riva A, Severgnini M, Luigiano C, Benetti A, Pontiroli AE, Morace G, Borghi E. Body Mass Index and Sex Affect Diverse Microbial Niches within the Gut. Front Microbiol. 2018;9:213.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 39]  [Cited by in F6Publishing: 37]  [Article Influence: 13.0]  [Reference Citation Analysis (0)]
16.  Odamaki T, Kato K, Sugahara H, Hashikura N, Takahashi S, Xiao JZ, Abe F, Osawa R. Age-related changes in gut microbiota composition from newborn to centenarian: a cross-sectional study. BMC Microbiol. 2016;16:90.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 485]  [Cited by in F6Publishing: 379]  [Article Influence: 97.0]  [Reference Citation Analysis (0)]
17.  Gudra D, Pupola D, Skenders G, Leja M, Radovica-Spalvina I, Gorskis H, Vangravs R, Fridmanis D. Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori-infected subjects before and 2 years after a single eradication event. Helicobacter. 2020;25:e12748.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 2]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
18.  Leeming ER, Johnson AJ, Spector TD, Le Roy CI. Effect of Diet on the Gut Microbiota: Rethinking Intervention Duration. Nutrients. 2019;11.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 89]  [Cited by in F6Publishing: 55]  [Article Influence: 44.5]  [Reference Citation Analysis (0)]
19.  Huang R, Ju Z, Zhou PK. A gut dysbiotic microbiota-based hypothesis of human-to-human transmission of non-communicable diseases. Sci Total Environ. 2020;745:141030.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 3]  [Article Influence: 4.0]  [Reference Citation Analysis (0)]
20.  Yanagi H, Tsuda A, Matsushima M, Takahashi S, Ozawa G, Koga Y, Takagi A. Changes in the gut microbiota composition and the plasma ghrelin level in patients with Helicobacter pylori-infected patients with eradication therapy. BMJ Open Gastroenterol. 2017;4:e000182.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 25]  [Article Influence: 7.8]  [Reference Citation Analysis (0)]
21.  Hsu PI, Pan CY, Kao JY, Tsay FW, Peng NJ, Kao SS, Chen YH, Tsai TJ, Wu DC, Tsai KW. Short-term and long-term impacts of Helicobacter pylori eradication with reverse hybrid therapy on the gut microbiota. J Gastroenterol Hepatol. 2019;34:1968-1976.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 16]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
22.  Hsu PI, Pan CY, Kao JY, Tsay FW, Peng NJ, Kao SS, Wang HM, Tsai TJ, Wu DC, Chen CL, Tsai KW; Taiwan Acid-related Disease (TARD) Study Group. Helicobacter pylori eradication with bismuth quadruple therapy leads to dysbiosis of gut microbiota with an increased relative abundance of Proteobacteria and decreased relative abundances of Bacteroidetes and Actinobacteria. Helicobacter. 2018;23:e12498.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 27]  [Cited by in F6Publishing: 27]  [Article Influence: 9.0]  [Reference Citation Analysis (0)]
23.  Martín-Núñez GM, Cornejo-Pareja I, Roca-Rodríguez MDM, Clemente-Postigo M, Cardona F, Fernández-García JC, Moreno-Indias I, Tinahones FJ. H. pylori Eradication Treatment Causes Alterations in the Gut Microbiota and Blood Lipid Levels. Front Med (Lausanne). 2020;7:417.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
24.  Liou JM, Lee YC, Wu MS. Treatment of Helicobacter pylori infection and its long-term impacts on gut microbiota. J Gastroenterol Hepatol. 2020;35:1107-1116.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 8]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
25.  Liou JM, Chen CC, Chang CM, Fang YJ, Bair MJ, Chen PY, Chang CY, Hsu YC, Chen MJ, Lee JY, Yang TH, Luo JC, Chen CY, Hsu WF, Chen YN, Wu JY, Lin JT, Lu TP, Chuang EY, El-Omar EM, Wu MS; Taiwan Gastrointestinal Disease and Helicobacter Consortium. Long-term changes of gut microbiota, antibiotic resistance, and metabolic parameters after Helicobacter pylori eradication: a multicentre, open-label, randomised trial. Lancet Infect Dis. 2019;19:1109-1120.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 43]  [Cited by in F6Publishing: 19]  [Article Influence: 43.0]  [Reference Citation Analysis (0)]
26.  Jakobsson HE, Jernberg C, Andersson AF, Sjölund-Karlsson M, Jansson JK, Engstrand L. Short-term antibiotic treatment has differing long-term impacts on the human throat and gut microbiome. PLoS One. 2010;5:e9836.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 645]  [Cited by in F6Publishing: 552]  [Article Influence: 58.6]  [Reference Citation Analysis (0)]
27.  Ye Q, Shao X, Shen R, Chen D, Shen J. Changes in the human gut microbiota composition caused by Helicobacter pylori eradication therapy: A systematic review and meta-analysis. Helicobacter. 2020;25:e12713.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 6]  [Article Influence: 8.0]  [Reference Citation Analysis (0)]
28.  Jones TA, Hernandez DZ, Wong ZC, Wandler AM, Guillemin K. The bacterial virulence factor CagA induces microbial dysbiosis that contributes to excessive epithelial cell proliferation in the Drosophila gut. PLoS Pathog. 2017;13:e1006631.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 15]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
29.  Hatakeyama M. Helicobacter pylori CagA and gastric cancer: a paradigm for hit-and-run carcinogenesis. Cell Host Microbe. 2014;15:306-316.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 251]  [Cited by in F6Publishing: 199]  [Article Influence: 35.9]  [Reference Citation Analysis (0)]
30.  Isomoto H, Moss J, Hirayama T. Pleiotropic actions of Helicobacter pylori vacuolating cytotoxin, VacA. Tohoku J Exp Med. 2010;220:3-14.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 49]  [Cited by in F6Publishing: 44]  [Article Influence: 4.5]  [Reference Citation Analysis (0)]
31.  Abreu MT, Peek RM Jr. Gastrointestinal malignancy and the microbiome. Gastroenterology. 2014;146:1534-1546.e3.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 163]  [Cited by in F6Publishing: 139]  [Article Influence: 23.3]  [Reference Citation Analysis (0)]
32.  Peek RM Jr, Fiske C, Wilson KT. Role of innate immunity in Helicobacter pylori-induced gastric malignancy. Physiol Rev. 2010;90:831-858.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 133]  [Cited by in F6Publishing: 124]  [Article Influence: 12.1]  [Reference Citation Analysis (0)]
33.  Imhann F, Bonder MJ, Vich Vila A, Fu J, Mujagic Z, Vork L, Tigchelaar EF, Jankipersadsing SA, Cenit MC, Harmsen HJ, Dijkstra G, Franke L, Xavier RJ, Jonkers D, Wijmenga C, Weersma RK, Zhernakova A. Proton pump inhibitors affect the gut microbiome. Gut. 2016;65:740-748.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 467]  [Cited by in F6Publishing: 389]  [Article Influence: 77.8]  [Reference Citation Analysis (0)]
34.  Jackson MA, Goodrich JK, Maxan ME, Freedberg DE, Abrams JA, Poole AC, Sutter JL, Welter D, Ley RE, Bell JT, Spector TD, Steves CJ. Proton pump inhibitors alter the composition of the gut microbiota. Gut. 2016;65:749-756.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 368]  [Cited by in F6Publishing: 311]  [Article Influence: 61.3]  [Reference Citation Analysis (0)]
35.  Heimesaat MM, Fischer A, Plickert R, Wiedemann T, Loddenkemper C, Göbel UB, Bereswill S, Rieder G. Helicobacter pylori induced gastric immunopathology is associated with distinct microbiota changes in the large intestines of long-term infected Mongolian gerbils. PLoS One. 2014;9:e100362.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 38]  [Cited by in F6Publishing: 38]  [Article Influence: 5.4]  [Reference Citation Analysis (0)]
36.  Waldum HL, Kleveland PM, Sørdal ØF. Helicobacter pylori and gastric acid: an intimate and reciprocal relationship. Therap Adv Gastroenterol. 2016;9:836-844.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 33]  [Cited by in F6Publishing: 16]  [Article Influence: 6.6]  [Reference Citation Analysis (0)]
37.  Kusters JG, van Vliet AH, Kuipers EJ. Pathogenesis of Helicobacter pylori infection. Clin Microbiol Rev. 2006;19:449-490.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1188]  [Cited by in F6Publishing: 581]  [Article Influence: 79.2]  [Reference Citation Analysis (0)]
38.  Guo Y, Zhang Y, Gerhard M, Gao JJ, Mejias-Luque R, Zhang L, Vieth M, Ma JL, Bajbouj M, Suchanek S, Liu WD, Ulm K, Quante M, Li ZX, Zhou T, Schmid R, Classen M, Li WQ, You WC, Pan KF. Effect of Helicobacter pylori on gastrointestinal microbiota: a population-based study in Linqu, a high-risk area of gastric cancer. Gut. 2020;69:1598-1607.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 35]  [Article Influence: 20.5]  [Reference Citation Analysis (0)]
39.  Haruma K, Mihara M, Okamoto E, Kusunoki H, Hananoki M, Tanaka S, Yoshihara M, Sumii K, Kajiyama G. Eradication of Helicobacter pylori increases gastric acidity in patients with atrophic gastritis of the corpus-evaluation of 24-h pH monitoring. Aliment Pharmacol Ther. 1999;13:155-162.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 104]  [Cited by in F6Publishing: 100]  [Article Influence: 4.7]  [Reference Citation Analysis (0)]
40.  Iijima K, Sekine H, Koike T, Imatani A, Ohara S, Shimosegawa T. Long-term effect of Helicobacter pylori eradication on the reversibility of acid secretion in profound hypochlorhydria. Aliment Pharmacol Ther. 2004;19:1181-1188.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 37]  [Cited by in F6Publishing: 35]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
41.  Sahara S, Sugimoto M, Vilaichone RK, Mahachai V, Miyajima H, Furuta T, Yamaoka Y. Role of Helicobacter pylori cagA EPIYA motif and vacA genotypes for the development of gastrointestinal diseases in Southeast Asian countries: a meta-analysis. BMC Infect Dis. 2012;12:223.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 53]  [Cited by in F6Publishing: 48]  [Article Influence: 5.9]  [Reference Citation Analysis (0)]