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Verma J, Anwar MT, Linz B, Backert S, Pachathundikandi SK. The Influence of Gastric Microbiota and Probiotics in Helicobacter pylori Infection and Associated Diseases. Biomedicines 2024; 13:61. [PMID: 39857645 PMCID: PMC11761556 DOI: 10.3390/biomedicines13010061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2024] [Revised: 12/23/2024] [Accepted: 12/24/2024] [Indexed: 01/27/2025] Open
Abstract
The role of microbiota in human health and disease is becoming increasingly clear as a result of modern microbiome studies in recent decades. The gastrointestinal tract is the major habitat for microbiota in the human body. This microbiota comprises several trillion microorganisms, which is equivalent to almost ten times the total number of cells of the human host. Helicobacter pylori is a known pathogen that colonizes the gastric mucosa of almost half of the world population. H. pylori is associated with several gastric diseases, including gastric cancer (GC) development. However, the impact of the gastric microbiota in the colonization, chronic infection, and pathogenesis is still not fully understood. Several studies have documented qualitative and quantitative changes in the microbiota's composition in the presence or absence of this pathogen. Among the diverse microflora in the stomach, the Firmicutes represent the most notable. Bacteria such as Prevotella sp., Clostridium sp., Lactobacillus sp., and Veillonella sp. were frequently found in the healthy human stomach. In contrast, H.pylori is very dominant during chronic gastritis, increasing the proportion of Proteobacteria in the total microbiota to almost 80%, with decreasing relative proportions of Firmicutes. Likewise, H. pylori and Streptococcus are the most abundant bacteria during peptic ulcer disease. While the development of H. pylori-associated intestinal metaplasia is accompanied by an increase in Bacteroides, the stomachs of GC patients are dominated by Firmicutes such as Lactobacillus and Veillonella, constituting up to 40% of the total microbiota, and by Bacteroidetes such as Prevotella, whereas the numbers of H. pylori are decreasing. This review focuses on some of the consequences of changes in the gastric microbiota and the function of probiotics to modulate H. pylori infection and dysbiosis in general.
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Affiliation(s)
- Jagriti Verma
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
| | - Md Tanveer Anwar
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
| | - Bodo Linz
- Chair of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Steffen Backert
- Chair of Microbiology, Department of Biology, Friedrich Alexander University Erlangen-Nürnberg, Staudtstr. 5, 91058 Erlangen, Germany
| | - Suneesh Kumar Pachathundikandi
- Department of Environmental Microbiology, School of Earth and Environmental Sciences, Babasaheb Bhimrao Ambedkar University, Vidya Vihar, Raebareli Road, Lucknow 226025, India
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Keikha M, Karbalaei M. Probiotics as the live microscopic fighters against Helicobacter pylori gastric infections. BMC Gastroenterol 2021; 21:388. [PMID: 34670526 PMCID: PMC8527827 DOI: 10.1186/s12876-021-01977-1] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2021] [Accepted: 10/15/2021] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is the causative agent of stomach diseases such as duodenal ulcer and gastric cancer, in this regard incomplete eradication of this bacterium has become to a serious concern. Probiotics are a group of the beneficial bacteria which increase the cure rate of H. pylori infections through various mechanisms such as competitive inhibition, co-aggregation ability, enhancing mucus production, production of bacteriocins, and modulating immune response. RESULT In this study, according to the received articles, the anti-H. pylori activities of probiotics were reviewed. Based on studies, administration of standard antibiotic therapy combined with probiotics plays an important role in the effective treatment of H. pylori infection. According to the literature, Lactobacillus casei, Lactobacillus reuteri, Lactobacillus rhamnosus GG, and Saccharomyces boulardii can effectively eradicate H. pylori infection. Our results showed that in addition to decrease gastrointestinal symptoms, probiotics can reduce the side effects of antibiotics (especially diarrhea) by altering the intestinal microbiome. CONCLUSION Nevertheless, antagonist activities of probiotics are H. pylori strain-specific. In general, these bacteria can be used for therapeutic purposes such as adjuvant therapy, drug-delivery system, as well as enhancing immune system against H. pylori infection.
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Affiliation(s)
- Masoud Keikha
- Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Karbalaei
- Department of Microbiology and Virology, School of Medicine, Jiroft University of Medical Sciences, Jiroft, Iran.
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Kouzu K, Tsujimoto H, Kishi Y, Ueno H, Shinomiya N. Role of Microbial Infection-Induced Inflammation in the Development of Gastrointestinal Cancers. MEDICINES 2021; 8:medicines8080045. [PMID: 34436224 PMCID: PMC8400127 DOI: 10.3390/medicines8080045] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 06/25/2021] [Revised: 08/05/2021] [Accepted: 08/13/2021] [Indexed: 12/12/2022]
Abstract
There has been increasing evidence that a local inflammatory response stimulates tumor cells to acquire metastatic potential, and the concept of inflammatory oncotaxis has been spreading in recent years. However, the interaction between microbial inflammation and the development of gastrointestinal cancer is still unclear. This review summarizes the present knowledge on the role of microbial inflammation in the development of gastrointestinal cancers from the perspective of molecular biological findings. Chronic inflammation caused by bacterial infection is known to induce cancers as exemplified by Helicobacter pylori, which is associated with the development of gastric cancer via the activation of the TLR4 pathway by bacterial lipopolysaccharide followed by cancer growth through CagA-MET signaling. In addition, the development of inflammatory bowel diseases has been known to become a risk factor for colorectal cancers, where inflammation caused by certain bacterial infections plays a key role. It is also known that the cancer microenvironment is associated with cancer growth. Moreover, infectious complication after surgery for gastrointestinal cancers may promote tumor progression via the stimulation of pathogen-associated molecular patterns and various inflammatory mediators secreted by immunocytes. Further research on the link between microbial inflammation and cancer progression is needed to drive a paradigm shift in cancer treatment.
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Affiliation(s)
- Keita Kouzu
- Department of Surgery, National Defense Medical College, Saitama 359-0042, Japan; (K.K.); (Y.K.); (H.U.)
| | - Hironori Tsujimoto
- Department of Surgery, National Defense Medical College, Saitama 359-0042, Japan; (K.K.); (Y.K.); (H.U.)
- Correspondence: ; Tel.: +81-4-2995-1637
| | - Yoji Kishi
- Department of Surgery, National Defense Medical College, Saitama 359-0042, Japan; (K.K.); (Y.K.); (H.U.)
| | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama 359-0042, Japan; (K.K.); (Y.K.); (H.U.)
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Dargenio C, Dargenio VN, Bizzoco F, Indrio F, Francavilla R, Cristofori F. Limosilactobacillus reuteri Strains as Adjuvants in the Management of Helicobacter pylori Infection. MEDICINA (KAUNAS, LITHUANIA) 2021; 57:733. [PMID: 34357014 PMCID: PMC8306855 DOI: 10.3390/medicina57070733] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 06/19/2021] [Revised: 07/10/2021] [Accepted: 07/13/2021] [Indexed: 01/10/2023]
Abstract
Helicobacter pylori (HP) is a Gram-negative bacterium which finds its suitable habitat in the stomach. The infection affects about half of the global population with high variability in prevalence among regions and for age. HP is the main causative agent of chronic active gastritis, peptic and duodenal ulcers, and may be the primary cause of gastric cancer or MALT lymphoma. Due to the high rate of failure of eradication therapy in various countries and the increase in antibiotic resistance reported in the literature, there is an ever wider need to seek alternative therapeutic treatments. Probiotics seem to be a promising solution. In particular, the Limosilactobacillus reuteri (L. reuteri) species is a Gram-positive bacterium and is commonly found in the microbiota of mammals. L. reuteri is able to survive the gastric acid environment and bile and to colonize the gastric mucosa. This species is able to inhibit the growth of several pathogenic bacteria through different mechanisms, keeping the homeostasis of the microbiota. In particular, it is able to secrete reuterin and reutericycline, substances that exhibit antimicrobial properties, among other molecules. Through the secretion of these and the formation of the biofilm, it has been found to strongly inhibit the growth of HP and, at higher concentrations, to kill it. Moreover, it reduces the expression of HP virulence factors. In clinical trials, L. reuteri has been shown to decrease HP load when used as a single treatment, but has not achieved statistical significance in curing infected patients. As an adjuvant of standard regimens with antibiotics and pump inhibitors, L. reuteri can be used not only to improve cure rates, but especially to decrease gastrointestinal symptoms, which are a common cause of lack of compliance and interruption of therapy, leading to new antibiotic resistance.
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Affiliation(s)
- Costantino Dargenio
- Interdisciplinary Department of Medicine, Pediatric Section, University of Bari, Children’s Hospital “Giovanni XXIII”, 70126 Bari, Italy; (C.D.); (V.N.D.); (F.B.); (F.C.)
| | - Vanessa Nadia Dargenio
- Interdisciplinary Department of Medicine, Pediatric Section, University of Bari, Children’s Hospital “Giovanni XXIII”, 70126 Bari, Italy; (C.D.); (V.N.D.); (F.B.); (F.C.)
| | - Francesca Bizzoco
- Interdisciplinary Department of Medicine, Pediatric Section, University of Bari, Children’s Hospital “Giovanni XXIII”, 70126 Bari, Italy; (C.D.); (V.N.D.); (F.B.); (F.C.)
| | - Flavia Indrio
- Department of Medical and Surgical Sciences, Pediatric Section, University of Foggia, 71122 Foggia, Italy;
| | - Ruggiero Francavilla
- Interdisciplinary Department of Medicine, Pediatric Section, University of Bari, Children’s Hospital “Giovanni XXIII”, 70126 Bari, Italy; (C.D.); (V.N.D.); (F.B.); (F.C.)
| | - Fernanda Cristofori
- Interdisciplinary Department of Medicine, Pediatric Section, University of Bari, Children’s Hospital “Giovanni XXIII”, 70126 Bari, Italy; (C.D.); (V.N.D.); (F.B.); (F.C.)
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Palrasu M, Zaika E, El-Rifai W, Que J, Zaika AI. Role of Bacterial and Viral Pathogens in Gastric Carcinogenesis. Cancers (Basel) 2021; 13:1878. [PMID: 33919876 PMCID: PMC8070847 DOI: 10.3390/cancers13081878] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2021] [Revised: 04/02/2021] [Accepted: 04/11/2021] [Indexed: 01/10/2023] Open
Abstract
Gastric cancer (GC) is one of the deadliest malignancies worldwide. In contrast to many other tumor types, gastric carcinogenesis is tightly linked to infectious events. Infections with Helicobacter pylori (H. pylori) bacterium and Epstein-Barr virus (EBV) are the two most investigated risk factors for GC. These pathogens infect more than half of the world's population. Fortunately, only a small fraction of infected individuals develops GC, suggesting high complexity of tumorigenic processes in the human stomach. Recent studies suggest that the multifaceted interplay between microbial, environmental, and host genetic factors underlies gastric tumorigenesis. Many aspects of these interactions still remain unclear. In this review, we update on recent discoveries, focusing on the roles of various gastric pathogens and gastric microbiome in tumorigenesis.
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Affiliation(s)
- Manikandan Palrasu
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Elena Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
| | - Wael El-Rifai
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
| | - Jianwen Que
- Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA;
| | - Alexander I. Zaika
- Department of Surgery, University of Miami, Miami, FL 33136, USA; (M.P.); (E.Z.); (W.E.-R.)
- Department of Veterans Affairs, Miami VA Healthcare System, Miami, FL 33136, USA
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Yang L, Zhang J, Xu J, Wei X, Yang J, Liu Y, Li H, Zhao C, Wang Y, Zhang L, Gai Z. Helicobacter pylori Infection Aggravates Dysbiosis of Gut Microbiome in Children With Gastritis. Front Cell Infect Microbiol 2019; 9:375. [PMID: 31781514 PMCID: PMC6859803 DOI: 10.3389/fcimb.2019.00375] [Citation(s) in RCA: 41] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/20/2019] [Accepted: 10/16/2019] [Indexed: 02/06/2023] Open
Abstract
Introduction:Helicobacter pylori infection consistently leads to chronic and low degree of inflammatory response in gastric mucosa and is closely related with gastrointestinal and extra-gastric diseases. Effects of local microbiome in the stomach have been studied in adults and children with H. pylori infection. It is, however, not known whether the intestinal microbial community differs in children with varying H. pylori infection. The aim of this study is to characterize the altered composition of microbiome induced by H. pylori infection and in gastritis. Materials and Methods: This study involved 154 individuals, including 50 children affected by H. pylori-induced gastritis, 42 children with H. pylori-negative gastritis, and 62 healthy controls. Gut microbiome composition was analyzed using 16S rRNA gene-based pyrosequencing. Fecal bacterial diversity and composition were then compared. Results: On the basis of an analysis of similarities and differences, we found that children with H. pylori-induced gastritis exhibited gut bacteria dysbiosis. The ratio of Firmicutes/Bacteroidetes (F:B) at the phylum level had dramatically decreased in H. pylori-positive gastritis group (HPG) and H. pylori-negative gastritis group (HNG), compared with the healthy control group (HCG). At the family and genus levels, relative abundance of Bacteroidaceae and Enterobacteriaceae was prevalent in HPG and HNG, whereas relative abundance of Lachnospiraceae, Bifidobacteriaceae, and Lactobacillaceae was seen in HCG. Prevalence of different taxa of gut microbiome at the class, order, family, and genus levels was also observed among the three groups. Conclusions: Gastritis can cause changes in composition of fecal microbiome, which is exacerbated by H. pylori infection. These changes in gut microbiome may be related to drug resistance and development of chronic gastrointestinal diseases.
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Affiliation(s)
- Lu Yang
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Jiaming Zhang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Junjie Xu
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Xuxia Wei
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Junjie Yang
- College of Life Science, Qilu Normal University, Jinan, China
| | - Yi Liu
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Hua Li
- Department of Digestive Disease, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Changying Zhao
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Ying Wang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Lei Zhang
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Beijing Advanced Innovation Center for Big Data-Based Precision Medicine, Beihang University, Beijing, China
| | - Zhongtao Gai
- Shandong Children's Microbiome Center, Qilu Children's Hospital of Shandong University, Jinan, China.,Research Institute of Pediatrics, Qilu Children's Hospital of Shandong University, Jinan, China
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Eslami M, Yousefi B, Kokhaei P, Jazayeri Moghadas A, Sadighi Moghadam B, Arabkari V, Niazi Z. Are probiotics useful for therapy of Helicobacter pylori diseases? Comp Immunol Microbiol Infect Dis 2019; 64:99-108. [PMID: 31174707 DOI: 10.1016/j.cimid.2019.02.010] [Citation(s) in RCA: 29] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2019] [Revised: 02/24/2019] [Accepted: 02/26/2019] [Indexed: 02/06/2023]
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Modification of the Gastric Mucosal Microbiota by a Strain-Specific Helicobacter pylori Oncoprotein and Carcinogenic Histologic Phenotype. mBio 2019; 10:mBio.00955-19. [PMID: 31138752 PMCID: PMC6538789 DOI: 10.1128/mbio.00955-19] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Microbial communities are essential for the maintenance of human health, and when these communities are altered, hosts can become susceptible to inflammation and disease. Dysbiosis contributes to gastrointestinal cancers, and specific bacterial species are associated with this phenotype. This study uses a robust and reproducible animal model to demonstrate that H. pylori infection induces gastric dysbiosis in a cagA-dependent manner and further that dysbiosis and altered microbial community structure parallel the severity of H. pylori-induced gastric injury. Ultimately, such models of H. pylori infection and cancer that can effectively evaluate multiple determinants simultaneously may yield effective strategies for manipulating the gastric microbiota to prevent the development of gastric cancer. Helicobacter pylori is the strongest risk factor for gastric adenocarcinoma; however, most infected individuals never develop this malignancy. Strain-specific microbial factors, such as the oncoprotein CagA, as well as environmental conditions, such as iron deficiency, augment cancer risk. Importantly, dysbiosis of the gastric microbiota is also associated with gastric cancer. To investigate the combinatorial effects of these determinants in an in vivo model of gastric cancer, Mongolian gerbils were infected with the carcinogenic cag+H. pylori strain 7.13 or a 7.13 cagA isogenic mutant, and microbial DNA extracted from gastric tissue was analyzed by 16S rRNA sequencing. Infection with H. pylori significantly increased gastric inflammation and injury, decreased α-diversity, and altered microbial community structure in a cagA-dependent manner. The effect of iron deficiency on gastric microbial communities was also investigated within the context of infection. H. pylori-induced injury was augmented under conditions of iron deficiency, but despite differences in gastric pathology, there were no significant differences in α- or β-diversity, phyla, or operational taxonomic unit (OTU) abundance among infected gerbils maintained on iron-replete or iron-depleted diets. However, when microbial composition was stratified based solely on the severity of histologic injury, significant differences in α- and β-diversity were present among gerbils harboring premalignant or malignant lesions compared to gerbils with gastritis alone. This study demonstrates that H. pylori decreases gastric microbial diversity and community structure in a cagA-dependent manner and that as carcinogenesis progresses, there are corresponding alterations in community structure that parallel the severity of disease.
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Zaman C, Osaki T, Furuta Y, Hojo F, Yonezawa H, Konno M, Kurata S, Hanawa T, Kamiya S. Enhanced infectivity of strains of Helicobacter pylori isolated from children compared with parental strains. J Med Microbiol 2019; 68:633-641. [PMID: 30806617 DOI: 10.1099/jmm.0.000918] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/20/2022] Open
Abstract
PURPOSE Intra-familial infection, mother-to-child infection, is considered to be one of the main routes of transmission for Helicobacter pylori, in developed countries such as Japan. A major role for intra-familial spread in the pathogenicity of H. pylori is now beyond controversy, although the major route of transmission remains poorly understood. We performed this study to clarify the factors determining intra-familial transmission. METHODOLOGY We used several H. pylori strains isolated from family members to compare infectivity. H. pylori K21 and K22 strains were isolated from the father and mother, and the K25 strain was isolated from the third child of the family. Mongolian gerbils were inoculated with H. pylori strains and the infectivity of three strains was compared in each experiment. In addition, the whole genome sequence, adhesion to gastric epithelial cells and the growth of static condition or continuous flow culture among three strains of H. pylori were analysed.Results/Key findings. Most of the colonies were determined as the same molecular type K25 in all of the four grouped animals and H. pylori K25 was observed as the dominant strain. The stronger adhesion capacity of the K25 strain was observed in comparison with the other two strains through in vitro analysis. By assessing the genomic profiles of H. pylori isolates from three strains, identified TnPZ regions were detected only in the K25 strain. CONCLUSION The infectivity of H. pylori isolates intra-familial infection and animal infection were prescribed by the adhesion capacity and molecular type of each strain.
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Affiliation(s)
- Cynthia Zaman
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Yoshikazu Furuta
- Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan
| | - Fuhito Hojo
- Department of Pediatrics, Sapporo Kosei General Hospital, Sapporo, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Mutsuko Konno
- Institute of Laboratory Animals, Graduate School of Medicine, Kyorin University, Mitaka, Tokyo, Japan
| | - Satoshi Kurata
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Tomoko Hanawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Mitaka, Tokyo, Japan
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What Roles Do Probiotics Play in the Eradication of Helicobacter pylori? Current Knowledge and Ongoing Research. Gastroenterol Res Pract 2018; 2018:9379480. [PMID: 30410538 PMCID: PMC6206577 DOI: 10.1155/2018/9379480] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/28/2018] [Revised: 09/23/2018] [Accepted: 09/26/2018] [Indexed: 12/14/2022] Open
Abstract
With the rising global prevalence of antibiotic resistance, the eradication rate of Helicobacter pylori (HP) is continuing to decrease. Probiotics are beneficial to human health and may be an adjunct therapy to increase the eradication rate of HP, lower treatment-associated side effects, and reduce HP-associated gastric inflammation. However, inconsistent test results have prevented conclusions about the therapeutic prowess of probiotics for HP. The mechanisms of actions of probiotics include the production of substances that inhibit or kill HP or compete with HP for the adhesion site on gastric epithelial cells. Probiotics can also reduce the release of inflammatory factors by regulating the local immune response of the host. We searched the available literature for full-length articles focusing on the role of probiotics in HP management. This review presents the latest advances in this area.
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Osaki T, Zaman C, Yonezawa H, Lin Y, Okuda M, Nozaki E, Hojo F, Kurata S, Hanawa T, Kikuchi S, Kamiya S. Influence of Intestinal Indigenous Microbiota on Intrafamilial Infection by Helicobacter pylori in Japan. Front Immunol 2018. [PMID: 29515585 PMCID: PMC5826345 DOI: 10.3389/fimmu.2018.00287] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Helicobacter pylori is a causative pathogen of chronic gastritis, gastric ulcer disease, and gastric cancer. Humans are known to be a natural host for H. pylori and tend to acquire the pathogen before the age of 5 years. The infection may then persist lifelong if eradication therapy is not applied. One of the modes of transmission of H. pylori is between family members, and therefore, the presence of infected family members is an important risk factor in children. However, other environmental factors have not been fully analyzed. The present study was performed to clarify whether and to what extent intestinal microbiota affect H. pylori intrafamilial infection. The fecal specimens from H. pylori-infected infants and H. pylori-infected and non-infected family members were collected in cohort studies conducted by Sasayama City, Hyogo Prefecture from 2010 to 2013. In total, 18 fecal DNA from 5 families were analyzed. Samples were amplified using 16S rRNA universal primers, and the amplicons were sequenced using the Ion PGM system. Principal-coordinate analysis demonstrated that there was no difference in intestinal microbiota between H. pylori-positive and H. pylori-negative groups. In intrafamilial comparison tests, the Manhattan distance of intestinal microbiota between the H. pylori-infected infant proband and H. pylori-negative mother was nearest in the family with low intestinal microbial diversity. However, in the family with the highest intestinal microbial diversity, the nearest Manhattan distance was shown between the H. pylori-infected infant proband and H. pylori-infected mother. The results in this study showed that the composition of the intestinal microbiota was very similar between members of the same family, and as such, colonization with organisms highly similar to the infected parent(s) may be a risk factor for H. pylori infection in children.
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Affiliation(s)
- Takako Osaki
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Cynthia Zaman
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Hideo Yonezawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Yingsong Lin
- Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan
| | - Masumi Okuda
- Department of Pediatrics, Aichi Medical University School of Medicine, Aichi, Japan.,Department of General Medicine and Community Health Science, Hyogo College of Medicine, Hyogo, Japan
| | - Eriko Nozaki
- Core Laboratory for Proteomics and Genomics, Kyorin University School of Medicine, Tokyo, Japan
| | - Fuhito Hojo
- Graduate School of Medicine, Institute of Laboratory Animals, Kyorin University, Tokyo, Japan
| | - Satoshi Kurata
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Tomoko Hanawa
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
| | - Shogo Kikuchi
- Department of Public Health, Aichi Medical University School of Medicine, Aichi, Japan
| | - Shigeru Kamiya
- Department of Infectious Diseases, Kyorin University School of Medicine, Tokyo, Japan
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12
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Lerner A, Arleevskaya M, Schmiedl A, Matthias T. Microbes and Viruses Are Bugging the Gut in Celiac Disease. Are They Friends or Foes? Front Microbiol 2017; 8:1392. [PMID: 28824555 PMCID: PMC5539691 DOI: 10.3389/fmicb.2017.01392] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2017] [Accepted: 07/10/2017] [Indexed: 12/17/2022] Open
Abstract
The links between microorganisms/viruses and autoimmunity are complex and multidirectional. A huge number of studies demonstrated the triggering impact of microbes and viruses as the major environmental factors on the autoimmune and inflammatory diseases. However, growing evidences suggest that infectious agents can also play a protective role or even abrogate these processes. This protective crosstalk between microbes/viruses and us might represent a mutual beneficial equilibrium relationship between two cohabiting ecosystems. The protective pathways might involve post-translational modification of proteins, decreased intestinal permeability, Th1 to Th2 immune shift, induction of apoptosis, auto-aggressive cells relocation from the target organ, immunosuppressive extracellular vesicles and down regulation of auto-reactive cells by the microbial derived proteins. Our analysis demonstrates that the interaction of the microorganisms/viruses and celiac disease (CD) is always a set of multidirectional processes. A deeper inquiry into the CD interplay with Herpes viruses and Helicobacter pylori demonstrates that the role of these infections, suggested to be potential CD protectors, is not as controversial as for the other infectious agents. The outcome of these interactions might be due to a balance between these multidirectional processes.
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Affiliation(s)
- Aaron Lerner
- The Ruth and Bruce Rappaport Faculty of Medicine, Technion Israel Institute of TechnologyHaifa, Israel
- Department of Research, AESKU.KIPP InstituteWendelsheim, Germany
| | - Marina Arleevskaya
- Central Research Laboratory, Kazan State Medical Academy KazanKazan, Russia
| | - Andreas Schmiedl
- Department of Research, AESKU.KIPP InstituteWendelsheim, Germany
| | - Torsten Matthias
- Department of Research, AESKU.KIPP InstituteWendelsheim, Germany
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Yang C, Cui MH. Virulence factors and pathogenic mechanism of Helicobacter pylori. Shijie Huaren Xiaohua Zazhi 2017; 25:857-864. [DOI: 10.11569/wcjd.v25.i10.857] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is closely related with some diseases such as chronic gastritis, peptic ulcer, gastric mucosa associated lymphoid tissue lymphoma, and gastric cancer. The pathogenicity of H. pylori mainly relies on its flagellum, spiral structure, lipopolysaccharide, cytotoxin associated protein A, and vacuolating cytotoxin A. Through complex pathogenic mechanisms, H. pylori causes various kinds of diseases. In this paper, we discuss the latest research progress in the understanding of the virulence factors and pathogenic mechanism of H. pylori.
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Abstract
The esophagus and stomach are host to their own population of bacteria, which differs in health and disease. Helicobacter pylori uniquely colonizes only gastric mucosa, but an increasing number of bacteria is now isolated from the gastric juice and gastric mucosa, including Lactobacillus. The presence of H pylori alters populations of other gastric bacteria with a marked reduction in diversity. Alterations in intragastric acidity may be the cause or the consequence of changes in the microbial populations of the stomach. Esophageal inflammation is associated with an altered microbiota in gastroesophageal reflux disease, Barrett's esophagus, eosinophilic esophagitis, and cancer.
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Helicobacter pylori, Cancer, and the Gastric Microbiota. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2017; 908:393-408. [PMID: 27573782 DOI: 10.1007/978-3-319-41388-4_19] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Gastric adenocarcinoma is one of the leading causes of cancer-related death worldwide and Helicobacter pylori infection is the strongest known risk factor for this disease. Although the stomach was once thought to be a sterile environment, it is now known to house many bacterial species leading to a complex interplay between H. pylori and other residents of the gastric microbiota. In addition to the role of H. pylori virulence factors, host genetic polymorphisms, and diet, it is now becoming clear that components of the gastrointestinal microbiota may also influence H. pylori-induced pathogenesis. In this chapter, we discuss emerging data regarding the gastric microbiota in humans and animal models and alterations that occur to the composition of the gastric microbiota in the presence of H. pylori infection that may augment the risk of developing gastric cancer.
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He C, Yang Z, Lu N. Imbalance of Gastrointestinal Microbiota in the Pathogenesis of Helicobacter pylori-Associated Diseases. Helicobacter 2016; 21:337-48. [PMID: 26876927 DOI: 10.1111/hel.12297] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/18/2022]
Abstract
The development of new nucleotide sequencing techniques and advanced bioinformatics tools has opened the field for studying the diversity and complexity of the gastrointestinal microbiome independent of traditional cultural methods. Owing largely to the gastric acid barrier, the human stomach was long thought to be sterile. The discovery of Helicobacter pylori, the gram-negative bacterium that infects upwards of 50% of the global population, has started a major paradigm shift in our understanding of the stomach as an ecologic niche for bacteria. Recent sequencing analysis of gastric microbiota showed that H. pylori was not alone and the interaction of H. pylori with those microorganisms might play a part in H. pylori-associated diseases such as gastric cancer. In this review, we summarize the available literature about the changes of gastrointestinal microbiota after H. pylori infection in humans and animal models, and discuss the possible underlying mechanisms including the alterations of the gastric environment, the secretion of hormones and the degree of inflammatory response. In general, information regarding the composition and function of gastrointestinal microbiome is still in its infancy, future studies are needed to elucidate whether and to what extent H. pylori infection perturbs the established microbiota. It is assumed that clarifying the role of gastrointestinal communities in H. pylori-associated diseases will provide an opportunity for translational application as a biomarker for the risk of serious H. pylori diseases and perhaps identify specific organisms for therapeutic eradication.
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Affiliation(s)
- Cong He
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Zhen Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China
| | - Nonghua Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi Province, China.
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Li K, Nie YQ. Relationship between gastrointestinal micro-ecological imbalance and development of gastric cancer. Shijie Huaren Xiaohua Zazhi 2016; 24:2324-2330. [DOI: 10.11569/wcjd.v24.i15.2324] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
The human body and microorganisms present in the body form a symbiotic system as the relationship between eukaryotes and prokaryotes. Therefore, it is not enough to study human diseases only in terms of human body. Recent studies have pointed out that microorganisms are involved in the occurrence of a large number of malignant tumors. According to a conservative estimate, at least 15% of cancer cases are associated with infectious agents. Gastric cancer is the second major cause of global cancer deaths. For a long period of time, researchers believe that Helicobacter pylori associated with chronic gastritis is the strongest risk factor for the occurrence of gastric cancer. However, with the progress of molecular biology research, it has been found that there is a close interaction between the large microbial flora and Helicobacter pylori in the gastrointestinal tract. The changes of microbial community composition have important effects on the formation, development and intervention of gastric cancer. This article will review the occurrence and development of gastrointestinal microorganism and gastric cancer.
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Abstract
After the discovery of Helicobacter pylori in 1983, the stomach was no longer considered a sterile environment. In 2015, evolving data shows that H. pylori is not the only inhabitant of the gastric mucosa. Using culture-independent methods of analysis, a non-H. pylori microbial community has been recently observed in the human stomach, the so-called human gastric microbiota, along with H. pylori itself. Increasing evidence supports the hypothesis that although H. pylori may be the most relevant, it is not the only local bacterial culprit leading to gastric diseases. Further studies are warranted to offer a better picture of the role and functions of gastric microbiota and to identify the best therapeutic modulators of gut microbiota for the management of gastric diseases.
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Affiliation(s)
- Gianluca Ianiro
- Division of Internal Medicine, Gastroenterology and Liver Disease, Department of Internal Medicine, "A. Gemelli" University Hospital, Rome, Italy
| | | | - Antonio Gasbarrini
- Division of Internal Medicine, Gastroenterology and Liver Disease, Department of Internal Medicine, "A. Gemelli" University Hospital, Rome, Italy
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Abstract
Humans depend on our commensal bacteria for nutritive, immune-modulating, and metabolic contributions to maintenance of health. However, this commensal community exists in careful balance that, if disrupted, enters dysbiosis; this has been shown to contribute to the pathogenesis of colon, gastric, esophageal, pancreatic, laryngeal, breast, and gallbladder carcinomas. This development is closely tied to host inflammation, which causes and is aggravated by microbial dysbiosis and increases vulnerability to pathogens. Advances in sequencing technology have increased our ability to catalog microbial species associated with various cancer types across the body. However, defining microbial biomarkers as cancer predictors presents multiple challenges, and existing studies identifying cancer-associated bacteria have reported inconsistent outcomes. Combining metabolites and microbiome analyses can help elucidate interactions between gut microbiota, metabolism, and the host. Ultimately, understanding how gut dysbiosis impacts host response and inflammation will be critical to creating an accurate picture of the role of the microbiome in cancer.
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Khosravi Y, Dieye Y, Loke MF, Goh KL, Vadivelu J. Streptococcus mitis induces conversion of Helicobacter pylori to coccoid cells during co-culture in vitro. PLoS One 2014; 9:e112214. [PMID: 25386948 PMCID: PMC4227722 DOI: 10.1371/journal.pone.0112214] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2014] [Accepted: 10/10/2014] [Indexed: 12/18/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a major gastric pathogen that has been associated with humans for more than 60,000 years. H. pylori causes different gastric diseases including dyspepsia, ulcers and gastric cancers. Disease development depends on several factors including the infecting H. pylori strain, environmental and host factors. Another factor that might influence H. pylori colonization and diseases is the gastric microbiota that was overlooked for long because of the belief that human stomach was a hostile environment that cannot support microbial life. Once established, H. pylori mainly resides in the gastric mucosa and interacts with the resident bacteria. How these interactions impact on H. pylori-caused diseases has been poorly studied in human. In this study, we analyzed the interactions between H. pylori and two bacteria, Streptococcus mitis and Lactobacillus fermentum that are present in the stomach of both healthy and gastric disease human patients. We have found that S. mitis produced and released one or more diffusible factors that induce growth inhibition and coccoid conversion of H. pylori cells. In contrast, both H. pylori and L. fermentum secreted factors that promote survival of S. mitis during the stationary phase of growth. Using a metabolomics approach, we identified compounds that might be responsible for the conversion of H. pylori from spiral to coccoid cells. This study provide evidences that gastric bacteria influences H. pylori physiology and therefore possibly the diseases this bacterium causes.
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Affiliation(s)
- Yalda Khosravi
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Yakhya Dieye
- Vice-chancellor's Office, University of Malaya, Kuala Lumpur, Malaysia
| | - Mun Fai Loke
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Khean Lee Goh
- Department of Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Jamuna Vadivelu
- Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
- * E-mail:
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