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Wu S, Luo Y, Wei F, Li Y, Fan J, Chen Y, Zhang W, Li X, Xu Y, Chen Z, Xia C, Hu M, Li P, Gu Q. Lactic acid bacteria target NF-κB signaling to alleviate gastric inflammation. Food Funct 2025; 16:3101-3119. [PMID: 40152095 DOI: 10.1039/d4fo06308b] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/29/2025]
Abstract
Helicobacter pylori (H. pylori) infection and the resulting gastric inflammation are major contributors to gastric cancer development. Probiotics, particularly Lactobacillus, are promising for their anti-inflammatory potential, yet their exact mechanisms in inhibiting H. pylori-induced inflammation are unclear. In our previous study, Lactiplantibacillus plantarum ZJ316 (L. plantarum ZJ316) demonstrated strong anti-inflammatory effects against H. pylori infection in vivo, but its precise mechanisms were not fully understood. Here, we aimed to investigate how L. plantarum ZJ316 inhibits the inflammatory response to H. pylori infection. Our results demonstrated that L. plantarum ZJ316 effectively reduced the expression of pro-inflammatory cytokines in H. pylori-infected AGS cells. Mechanistically, L. plantarum ZJ316 inhibited the NF-κB signaling pathway by preventing the degradation of IκBα, suppressing p65 phosphorylation, and blocking the nuclear translocation of phosphorylated p65. Treatment with the NF-κB inhibitor BAY 11-7082 further decreased tumor necrosis factor-α (TNF-α), interleukin-8 (IL-8), and interleukin-1β (IL-1β) levels, confirming the inhibitory effect of L. plantarum ZJ316 on the NF-κB pathway. In H. pylori-infected mice, oral administration of L. plantarum ZJ316 significantly alleviated inflammatory cell infiltration, reduced TNF-α and pepsinogen II (PGII) levels, and increased interleukin-10 (IL-10) levels in serum. A comparative metagenomic analysis of the gastric microbiota revealed a decrease in Prevotella and Desulfovibrio, alongside an increase in Ligilactobacillus and Akkermansia, supporting the protective effects of L. plantarum ZJ316 and correlating with their decreased inflammatory response. In summary, administration of L. plantarum ZJ316 demonstrated robust anti-inflammatory effects against H. pylori infection by suppressing NF-κB signaling and promoting favorable changes in the gastric microbiota composition. Therefore, L. plantarum ZJ316 holds promise as a novel functional food for protecting the body against H. pylori infection.
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Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yuenuo Luo
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yanan Li
- School of Food Science and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, Jiangsu 210023, China
| | - Jiayi Fan
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Wenjie Zhang
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Xuelong Li
- Hangzhou Helixinjian Industry Co., Ltd, No. 48 Zijinghua Road, Gudang Street, Xihu District, Hangzhou, Zhejiang 310050, China
| | - Yang Xu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Chenlan Xia
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Mingyang Hu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, Zhejiang Gongshang University, Hangzhou, Zhejiang 310018, China.
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Lin L, Li W, Yan L, Guo X, Zhuang M, Chen F, Ye W. Comparison of gastric microbiota in patients with different gastric lesions in high and low risk areas of gastric cancer. BMC Microbiol 2025; 25:202. [PMID: 40205356 PMCID: PMC11984132 DOI: 10.1186/s12866-025-03926-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2024] [Accepted: 03/24/2025] [Indexed: 04/11/2025] Open
Abstract
BACKGROUND Variation in gastric cancer (GC) incidence across different geographic areas persists, even when there are similar prevalence rates of Helicobacter pylori (H. pylori) infection. An extensive examination of the gastric microbiota in populations from both high- and low-risk regions of GC could help explain the geographical disparities in GC incidence. METHODS This study enrolled a total of 130 patients with superficial gastritis (SG) and precancerous lesions of gastric cancer (PLGC) from a high-risk area for GC and 205 patients from a low-risk area. Gastric microbial profiling was performed using 16 S rRNA gene sequencing to analyze differences in microbial composition between regions and lesion types. RESULTS The study revealed significant differences in gastric microbial profiles between patients from high- and low-risk regions, particularly in PLGC patients. PLGC patients from the low-risk region exhibited higher microbial richness than those from the high-risk area, with marked distinctions in microbial community structure between the two regions. Specific differences in microbial composition were observed at the phylum and genus levels between different regions. Six bacterial genera, including Selenomonas and Peptostreptococcus, were identified as enriched in PLGC patients from the high-risk area. Additionally, there was a noticeable imbalance in the microbiota of the gastric mucosal lining during the progression of gastric lesions. CONCLUSION This comparative analysis highlights the potential impact of the gastric microbiome in the development of GC and suggests that regional differences in microbial profiles may provide clues to the varying incidence rates of GC.
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Affiliation(s)
- Liying Lin
- Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China
| | - Wanxin Li
- Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China
| | - Lingjun Yan
- Department of Neurosurgery, The First Affiliated Hospital, Fujian Medical University, Fuzhou, 350005, Fujian, China
- Department of Neurosurgery, Binhai Campus of the First Affiliated Hospital, National Regional Medical Center, Fujian Medical University, Fuzhou, 350212, Fujian, China
| | - Xiaoxiong Guo
- Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China
| | - Mingkai Zhuang
- Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China
| | - Fenglin Chen
- Department of Gastroenterology and Fujian Institute of Digestive Disease, Fujian Medical University Union Hospital, Fuzhou, 350001, Fujian, China.
| | - Weimin Ye
- Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, 350000, China.
- Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, 17177, Sweden.
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Jeong H, Lee B, Cho SY, Lee Y, Kim J, Hur S, Cho K, Kim KH, Kim SH, Nam KT. Microbiota-derived short-chain fatty acids determine stem cell characteristics of gastric chief cells. Dev Cell 2025; 60:599-612.e6. [PMID: 39642880 DOI: 10.1016/j.devcel.2024.11.007] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/06/2023] [Revised: 08/07/2024] [Accepted: 11/08/2024] [Indexed: 12/09/2024]
Abstract
The gastric mucosa is a highly dynamic tissue that undergoes constant self-renewal through stem cell differentiation. Chief cells maintain a quiescent state in homeostasis but are responsible for regeneration after injury. Although the role of microbiome-host interactions in the intestine is well studied, less is known about these interactions in the stomach. Using the mouse organoid and germ-free mouse models, we show that microbiota-derived short-chain fatty acids (SCFAs) suppress the proliferation of chief cells in mice. This effect is mediated by activation of G-protein-coupled receptor 43. Most importantly, through metabolomics and transplantation studies, we show butyrate-producing Lactobacillus intestinalis modulates the proliferation of chief cells in mice. Our findings identify a mechanism by which the microbiota regulates the cell characteristics of chief cells, providing insight into the complex interplay between the host and its microbial environment and the mechanisms underlying gastric homeostasis, with potential therapeutic implications for gastric diseases.
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Affiliation(s)
- Haengdueng Jeong
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Buhyun Lee
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Soo Young Cho
- Department of Molecular and Life Science, Hanyang University, Ansan, Republic of Korea
| | - Yura Lee
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Jiseon Kim
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Sumin Hur
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Kyungrae Cho
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Kwang H Kim
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Sung-Hee Kim
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
| | - Ki Taek Nam
- Department of Biomedical Science, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
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Hasan AM, Cavalu S, Kira AY, Hamad RS, Abdel-Reheim MA, Elmorsy EA, El-kott AF, Morsy K, AlSheri AS, Negm S, Saber S. Localized Drug Delivery in Different Gastrointestinal Cancers: Navigating Challenges and Advancing Nanotechnological Solutions. Int J Nanomedicine 2025; 20:741-770. [PMID: 39845772 PMCID: PMC11752831 DOI: 10.2147/ijn.s502833] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2024] [Accepted: 12/18/2024] [Indexed: 01/24/2025] Open
Abstract
Different types of cancers affect the gastrointestinal tract (GIT), starting from the oral cavity and extending to the colon. In general, most of the current research focuses on the systemic delivery of the therapeutic agents, which leads to undesired side effects and a limited enhancement in the therapeutic outcomes. As a result, localized delivery within gastrointestinal (GI) cancers is favorable in overcoming these limitations. However, the localized delivery via oral administration faces many challenges related to the complex structure of GIT (varied pH levels and transit times) as well as the harsh environment within tumor cells (hypoxia, efflux pumps, and acidity). To overcome these obstacles, nano-drug delivery systems (NDDs) have been designed and proved their potential by exploiting these challenges in favor of offering a specific delivery to the desired target. The current review begins with an overview of different GI cancers and their impact globally. Then, it discusses the current treatment approaches and their corresponding limitations. Additionally, the different challenges associated with localized drug delivery for GI cancers are summarized. Finally, the review discusses in detail the recent therapeutic and diagnostic applications of NDDs that have been conducted in oral, esophageal, gastric, colon, and liver cancers, aiming to offer valuable insights into the current and future state of utilizing NDDs for the local treatment of GI cancers.
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Affiliation(s)
- Alexandru Madalin Hasan
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410087, Romania
| | - Simona Cavalu
- Department of Preclinical Sciences, Faculty of Medicine and Pharmacy, University of Oradea, Oradea, 410087, Romania
| | - Ahmed Y Kira
- Department of Pharmaceutics, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt
| | - Rabab S Hamad
- Biological Sciences Department, College of Science, King Faisal University, Al Ahsa, 31982, Saudi Arabia
| | - Mustafa Ahmed Abdel-Reheim
- Department of Pharmaceutical Sciences, College of Pharmacy, Shaqra University, Shaqra, 11961, Saudi Arabia
| | - Elsayed A Elmorsy
- Department of Pharmacology and Therapeutics, College of Medicine, Qassim University, Buraidah, 51452, Saudi Arabia
| | - Attalla F El-kott
- Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia
- Department of Zoology, Faculty of Science, Damanhour University, Damanhour, Egypt
| | - Kareem Morsy
- Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia
- Department of Zoology, Faculty of Science, Cairo University, Cairo, Egypt
| | - Ali S AlSheri
- Department of Biology, College of Science, King Khalid University, Abha, Saudi Arabia
| | - Sally Negm
- Department of Life Sciences, College of Science and Art, Mahyel Aseer, King Khalid University, Abha, 62529, Saudi Arabia
| | - Sameh Saber
- Department of Pharmacology, Faculty of Pharmacy, Delta University for Science and Technology, Gamasa, 11152, Egypt
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Hu J, Cao J, Huang S, Chen Y. ITGAX promotes gastric cancer progression via epithelial-mesenchymal transition pathway. Front Pharmacol 2025; 15:1536478. [PMID: 39845786 PMCID: PMC11750855 DOI: 10.3389/fphar.2024.1536478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/29/2024] [Accepted: 12/23/2024] [Indexed: 01/24/2025] Open
Abstract
Gastric cancer is the fifth most common cancer and the fourth leading cause of cancer-related deaths worldwide, accounting for nearly 800,000 fatalities annually. ITGAX (Integrin alpha X) is closely associated with immune cells, such as macrophages and dendritic cells. Its involvement in gastric cancer was identified through an analysis of The Gene Expression Omnibus (GEO) database, which highlighted ITGAX as one of four key gastric cancer-related genes. Our study demonstrates that ITGAX expression is significantly elevated in tumor tissues compared to normal tissues and is positively correlated with clinical prognosis in gastric cancer patients from the GEO database. Moreover, ITGAX enhanced cell proliferation, invasion, and tumorigenic capacity in mouse models. Furthermore, we explored the underlying role of ITGAX using Kyoto Encyclopedia of Genes and Genomes (KEGG) and protein-protein interaction networks (PPI) analysis. Our findings reveal that ITGAX promotes gastric cancer progression by driving epithelial-mesenchymal transition pathway (EMT), suggesting its potential as a biomarker for early diagnosis and prognosis in gastric cancer.
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Affiliation(s)
- Jiali Hu
- Department of Oncology, The Second Affiliated Hospital of Nanchang University, Nanchang, China
| | - Jing Cao
- School of Pharmacy, Jiangxi University of Traditional Chinese Medicine, Nanchang, China
| | - Shanshan Huang
- Department of Oncology, The First Affiliated Hospital of Nanchang University, Nanchang, China
| | - Yang Chen
- Ganjiang Chinese Medicine Innovation Center, Nanchang, China
- Key Laboratory of Phytochemistry and Natural Medicines, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, China
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Giddings HJ, Teodósio A, Jones J, McMurray JL, Hunter K, Alame R, Gardiner I, Abdawn Z, Butterworth W, Henderson IR, Cole JA, Shannon‐Lowe CD, Rossiter‐Pearson AE. The Gastric Microbiota Invade the Lamina Propria in Helicobacter pylori-Associated Gastritis and Precancer. Helicobacter 2025; 30:e70016. [PMID: 40011208 PMCID: PMC11865006 DOI: 10.1111/hel.70016] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/10/2024] [Revised: 01/21/2025] [Accepted: 01/28/2025] [Indexed: 02/28/2025]
Abstract
BACKGROUND Stomach cancer is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori is the main risk factor for gastric adenocarcinoma (GAC), yet the precise mechanism underpinning this association remains controversial. Gastric intestinal metaplasia (GIM) represents the precancerous stage and follows H. pylori-associated chronic gastritis (CG). Sequencing studies have revealed fewer H. pylori and more non-H. pylori bacteria in GAC. However, the spatial organization of the gastric microbiota in health and disease is unknown. MATERIALS AND METHODS Here, we have combined RNA in situ hybridization and immunohistochemistry to detect H. pylori, non-H. pylori bacteria, and host cell markers (E-cadherin, Mucins 5AC and 2) on tissue sections from patients with CG (n = 15) and GIM (n = 17). RESULTS Quantitative analysis of whole slide scans revealed significant correlations of H. pylori and other bacteria in CG and GIM. In contrast to sequencing studies, significantly fewer non-H. pylori bacteria were detected in H. pylori-negative patients. Importantly, whilst H. pylori exclusively colonized the gastric glands, non-H. pylori bacteria invaded the lamina propria in 6/9 CG and 8/10 GIM H. pylori-positive patients. A rapid and cost-effective modified Gram stain was used to confirm these findings and enabled detection of non-H. pylori bacteria in GIM samples. CONCLUSIONS The invasion of the gastric lamina propria by non-H. pylori bacteria during H. pylori-associated CG and GIM represents an overlooked phenomenon in cancer progression. Further work must determine the mechanisms underlying the synergistic roles of H. pylori and other bacteria in carcinogenesis. This observation should redirect attempts to prevent, diagnose, and treat GAC.
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Affiliation(s)
- Harriet J. Giddings
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Ana Teodósio
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Jordanne Jones
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Jack L. McMurray
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
- Rheumatology Research GroupUniversity of BirminghamBirminghamUK
| | - Kelly Hunter
- Birmingham Tissue Analytics, University of BirminghamBirminghamUK
| | - Riad Alame
- Queen Elizabeth HospitalUniversity Hospital Birmingham NHS Foundation TrustBirminghamUK
| | - Isaac Gardiner
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Zainab Abdawn
- Queen Elizabeth HospitalUniversity Hospital Birmingham NHS Foundation TrustBirminghamUK
| | - William Butterworth
- Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Ian R. Henderson
- Institute for Molecular BiosciencesUniversity of QueenslandBrisbaneAustralia
| | - Jeffrey A. Cole
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
| | - Claire D. Shannon‐Lowe
- Department of Immunology and Immunotherapy, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
| | - Amanda E. Rossiter‐Pearson
- Institute of Microbiology and InfectionUniversity of BirminghamBirminghamUK
- Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and HealthUniversity of BirminghamBirminghamUK
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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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8
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Gabrielli M, Zileri Dal Verme L, Zocco MA, Nista EC, Ojetti V, Gasbarrini A. The Role of the Gastrointestinal Microbiota in Parkinson's Disease. Biomolecules 2024; 15:26. [PMID: 39858421 PMCID: PMC11764295 DOI: 10.3390/biom15010026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 12/19/2024] [Accepted: 12/26/2024] [Indexed: 01/27/2025] Open
Abstract
BACKGROUND/OBJECTIVES Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the loss of dopaminergic neurons leading to debilitating motor and non-motor symptoms. Beyond its well-known neurological features, emerging evidence underscores the pivotal role of the gut-brain axis and gastrointestinal microbiota in PD pathogenesis. Dysbiosis has been strongly linked to PD and is associated with increased intestinal permeability, chronic inflammation, and the production of neurotoxic metabolites that may exacerbate neuronal damage. METHODS This review delves into the complex interplay between PD and dysbiosis, shedding light on two peculiar subsets of dysbiosis, Helicobacter pylori infection and small-intestinal bacterial overgrowth. These conditions may not only contribute to PD progression but also influence therapeutic responses such as L-dopa efficacy. CONCLUSIONS The potential to modulate gut microbiota through probiotics, prebiotics, and synbiotics; fecal microbiota transplantation; and antibiotics represents a promising frontier for innovative PD treatments. Despite this potential, the current evidence is limited by small sample sizes and methodological variability across studies. Rigorous, large-scale, randomized placebo-controlled trials with standardized treatments in terms of composition, dosage, and duration are urgently needed to validate these findings and pave the way for microbiota-based therapeutic strategies in PD management.
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Affiliation(s)
- Maurizio Gabrielli
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.Z.D.V.); (M.A.Z.); (E.C.N.); (A.G.)
| | - Lorenzo Zileri Dal Verme
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.Z.D.V.); (M.A.Z.); (E.C.N.); (A.G.)
| | - Maria Assunta Zocco
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.Z.D.V.); (M.A.Z.); (E.C.N.); (A.G.)
| | - Enrico Celestino Nista
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.Z.D.V.); (M.A.Z.); (E.C.N.); (A.G.)
| | - Veronica Ojetti
- Internal Medicine Department, San Carlo di Nancy Hospital, Università UniCamillus, 00131 Rome, Italy;
| | - Antonio Gasbarrini
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, 00168 Rome, Italy; (L.Z.D.V.); (M.A.Z.); (E.C.N.); (A.G.)
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9
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Boziki M, Theotokis P, Kesidou E, Nella M, Bakirtzis C, Karafoulidou E, Tzitiridou-Chatzopoulou M, Doulberis M, Kazakos E, Deretzi G, Grigoriadis N, Kountouras J. Impact of Mast Cell Activation on Neurodegeneration: A Potential Role for Gut-Brain Axis and Helicobacter pylori Infection. Neurol Int 2024; 16:1750-1778. [PMID: 39728753 DOI: 10.3390/neurolint16060127] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2024] [Revised: 11/08/2024] [Accepted: 12/03/2024] [Indexed: 12/28/2024] Open
Abstract
BACKGROUND The innate immune response aims to prevent pathogens from entering the organism and/or to facilitate pathogen clearance. Innate immune cells, such as macrophages, mast cells (MCs), natural killer cells and neutrophils, bear pattern recognition receptors and are thus able to recognize common molecular patterns, such as pathogen-associated molecular patterns (PAMPs), and damage-associated molecular patterns (DAMPs), the later occurring in the context of neuroinflammation. An inflammatory component in the pathology of otherwise "primary cerebrovascular and neurodegenerative" disease has recently been recognized and targeted as a means of therapeutic intervention. Activated MCs are multifunctional effector cells generated from hematopoietic stem cells that, together with dendritic cells, represent first-line immune defense mechanisms against pathogens and/or tissue destruction. METHODS This review aims to summarize evidence of MC implication in the pathogenesis of neurodegenerative diseases, namely, Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, and multiple sclerosis. RESULTS In view of recent evidence that the gut-brain axis may be implicated in the pathogenesis of neurodegenerative diseases and the characterization of the neuroinflammatory component in the pathology of these diseases, this review also focuses on MCs as potential mediators in the gut-brain axis bi-directional communication and the possible role of Helicobacter pylori, a gastric pathogen known to alter the gut-brain axis homeostasis towards local and systemic pro-inflammatory responses. CONCLUSION As MCs and Helicobacter pylori infection may offer targets of intervention with potential therapeutic implications for neurodegenerative disease, more clinical and translational evidence is needed to elucidate this field.
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Affiliation(s)
- Marina Boziki
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Paschalis Theotokis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Evangelia Kesidou
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Nella
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Christos Bakirtzis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Eleni Karafoulidou
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Maria Tzitiridou-Chatzopoulou
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Midwifery Department, School of Healthcare Sciences, University of West Macedonia, Koila, 50100 Kozani, Greece
| | - Michael Doulberis
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Gastroklinik, Private Gastroenterological Practice, 8810 Horgen, Switzerland
- Division of Gastroenterology and Hepatology, Medical University Department, 5001 Aarau, Switzerland
| | - Evangelos Kazakos
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
| | - Georgia Deretzi
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
- Department of Neurology, Papageorgiou General Hospital, 54629 Thessaloniki, Greece
| | - Nikolaos Grigoriadis
- Laboratory of Experimental Neurology and Neuroimmunology, the Multiple Sclerosis Center, 2nd Department of Neurology, AHEPA University Hospital, Aristotle University of Thessaloniki, 54636 Thessaloniki, Greece
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, 54642 Thessaloniki, Greece
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10
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Petkevicius V, Lehr K, Kupcinskas J, Link A. Fusobacterium nucleatum: Unraveling its potential role in gastric carcinogenesis. World J Gastroenterol 2024; 30:3972-3984. [PMID: 39351058 PMCID: PMC11438658 DOI: 10.3748/wjg.v30.i35.3972] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 08/09/2024] [Accepted: 08/27/2024] [Indexed: 09/13/2024] Open
Abstract
Fusobacterium nucleatum (F. nucleatum) is a Gram-negative anaerobic bacterium that plays a key role in the development of oral inflammation, such as periodontitis and gingivitis. In the last 10 years, F. nucleatum has been identified as a prevalent bacterium associated with colorectal adenocarcinoma and has also been linked to cancer progression, metastasis and poor disease outcome. While the role of F. nucleatum in colon carcinogenesis has been intensively studied, its role in gastric carcinogenesis is still poorly understood. Although Helicobacter pylori infection has historically been recognized as the strongest risk factor for the development of gastric cancer (GC), with recent advances in DNA sequencing technology, other members of the gastric microbial community, and F. nucleatum in particular, have received increasing attention. In this review, we summarize the existing knowledge on the involvement of F. nucleatum in gastric carcinogenesis and address the potential translational and clinical significance of F. nucleatum in GC.
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Affiliation(s)
- Vytenis Petkevicius
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
| | - Konrad Lehr
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
| | - Juozas Kupcinskas
- Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas 44307, Lithuania
- Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas 50161, Lithuania
| | - Alexander Link
- Department of Gastroenterology, Hepatology and Infectious Diseases, Otto-von-Guericke University Hospital, Magdeburg 39120, Germany
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11
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Chatterjee S, Leach ST, Lui K, Mishra A. Symbiotic symphony: Understanding host-microbiota dialogues in a spatial context. Semin Cell Dev Biol 2024; 161-162:22-30. [PMID: 38564842 DOI: 10.1016/j.semcdb.2024.03.001] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2023] [Revised: 02/23/2024] [Accepted: 03/20/2024] [Indexed: 04/04/2024]
Abstract
Modern precision sequencing techniques have established humans as a holobiont that live in symbiosis with the microbiome. Microbes play an active role throughout the life of a human ranging from metabolism and immunity to disease tolerance. Hence, it is of utmost significance to study the eukaryotic host in conjunction with the microbial antigens to obtain a complete picture of the host-microbiome crosstalk. Previous attempts at profiling host-microbiome interactions have been either superficial or been attempted to catalogue eukaryotic transcriptomic profile and microbial communities in isolation. Additionally, the nature of such immune-microbial interactions is not random but spatially organised. Hence, for a holistic clinical understanding of the interplay between hosts and microbiota, it's imperative to concurrently analyze both microbial and host genetic information, ensuring the preservation of their spatial integrity. Capturing these interactions as a snapshot in time at their site of action has the potential to transform our understanding of how microbes impact human health. In examining early-life microbial impacts, the limited presence of communities compels analysis within reduced biomass frameworks. However, with the advent of spatial transcriptomics we can address this challenge and expand our horizons of understanding these interactions in detail. In the long run, simultaneous spatial profiling of host-microbiome dialogues can have enormous clinical implications especially in gaining mechanistic insights into the disease prognosis of localised infections and inflammation. This review addresses the lacunae in host-microbiome research and highlights the importance of profiling them together to map their interactions while preserving their spatial context.
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Affiliation(s)
- Soumi Chatterjee
- Telethon Kids Institute, Perth Children Hospital, Perth, Western Australia 6009, Australia; Curtin Medical School, Curtin University, Perth, Western Australia 6102, Australia
| | - Steven T Leach
- Discipline Paediatrics, School of Clinical Medicine, University of New South Wales, Sydney 2052, Australia
| | - Kei Lui
- Department of Newborn Care, Royal Hospital for Women and Discipline of Paediatrics and Child Health, School of Clinical Medicine, Faculty of Medicine, University of New South Wales, Sydney 2052, Australia
| | - Archita Mishra
- Telethon Kids Institute, Perth Children Hospital, Perth, Western Australia 6009, Australia; Curtin Medical School, Curtin University, Perth, Western Australia 6102, Australia.
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12
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Kirkik D, Kalkanli Tas S, Tanoglu A. Unraveling the blood microbiome: novel insights into inflammasome responses in Crohn's disease. Eur J Gastroenterol Hepatol 2024; 36:975-984. [PMID: 38251441 DOI: 10.1097/meg.0000000000002695] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/23/2024]
Abstract
OBJECTIVE Crohn's disease (CD), an inflammatory bowel disease with unknown etiology, is influenced by genetic, environmental, and immunological factors. This study aimed to analyze the blood microbiome and inflammasome responses, emphasizing NLRP3 protein expression and IL-1β and IL-18 plasma levels, between Crohn's patients and healthy subjects. METHODS A total of 40 volunteers were included in this study. The 16S rRNA technique was used to sequence the V3-V4 regions of the blood sample. NLRP3 protein levels in plasma were ascertained through Western Blot, and IL-1β and IL-18 plasma profiles were examined using ELISA. RESULTS Analysis highlighted five unique phyla in patients' plasma, emphasizing the role of the blood microbiome in CD. Compared to controls, Crohn's patients exhibited elevated NLRP3 protein expression. Plasma IL-1β levels were diminished in patients ( P = 0.0041), whereas IL-18 levels were comparably higher ( P = 0.8209). In patients with CD, the presence of Staphylococcus sciuri in blood samples highlights its potential role in the disease's onset. The study also underscored the interplay between dietary habits, specifically increased meat consumption, and the progression of CD. CONCLUSION Our pioneering research discerns the variations in the blood microbiome and inflammasome responses between Crohn's patients and healthy individuals. Significant microbiome alterations and the detection of the Staphylococcus sciuri pathogen in Crohn's patients were notable. The pronounced NLRP3 protein in patients suggests its potential as a diagnostic biomarker. Future explorations into IL-1β and IL-18 pathways promise to unveil innovative insights into CD.
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Affiliation(s)
- Duygu Kirkik
- Hamidiye Medicine Faculty, Department of Medical Biology, University of Health Sciences, Turkey
| | - Sevgi Kalkanli Tas
- Hamidiye Medicine Faculty, Department of Immunology, University of Health Sciences, Turkey
| | - Alpaslan Tanoglu
- Department of Internal Medicine, Division of Gastroenterology, Bahcesehir University and School of Medicine, Istanbul, Turkey
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13
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Zhang J, Zhang Z, Shen D. Upregulated LncRNA-LINC00659 expression by H. pylori infection promoted the progression of gastritis to cancer by regulating PTBP1 expression. INDIAN J PATHOL MICR 2024; 67:510-517. [PMID: 38394397 DOI: 10.4103/ijpm.ijpm_48_23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2023] [Accepted: 05/23/2023] [Indexed: 02/25/2024] Open
Abstract
CONTEXT Helicobacter pylori ( H. pylori ), a spiral-shaped bacterium, is closely associated with chronic, progressive gastric mucosal damage, gastric atrophy, and even gastric cancer (GC). An increasing number of studies have addressed the correlation between long noncoding RNAs (lncRNAs) and H. pylori pathogenicity in GC. OBJECTIVE In this study, we found that the expression level of LINC00659 gradually increased in the progression from atrophic gastritis, intestinal metaplasia, and dysplasia to GC in H. pylori -infected patients. Thus, we aimed to further explore the function of LINC00659 in the progression of gastritis to cancer under H. pylori infection. MATERIALS AND METHODS StarBase predictions, ribonucleic acid (RNA)-binding protein immunoprecipitation assays, and gene ontology functional annotation (GO)/Kyoto encyclopedia of genes and genomes (KEGG) pathway analysis were performed to identify the RNA-binding proteins of LINC00659; moreover, qRT‒PCR, western blotting, RNA interference, and immunofluorescence assays were used to investigate the function of LINC00659. RESULTS LINC00659 bound directly to the RNA-binding protein polypyrimidine tract-binding protein (PTBP1). Importantly, qRT‒PCR and western blot assays demonstrated that PTBP1 expression increased in the progression from inflammation to cancer in the stomach of H. pylori -infected patients and H. pylori -infected GES-1 cells. However, LINC00659 knockdown downregulated PTBP1 expression and inhibited PTBP1 binding under H. pylori infection. Finally, LINC00659 knockdown significantly reduced H. pylori -induced human gastric epithelial cell senescence and suppressed interleukin (IL)-6 and IL-8 secretion by reducing the phosphorylation level of NF-κB p65. CONCLUSIONS This study indicated that LINC00659 may have the potential to be a novel promising prognostic and therapeutic marker for H. pylori -associated gastric diseases.
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Affiliation(s)
- Jiani Zhang
- School of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, P. R. China
| | - Zhengbo Zhang
- Department of Gastroenterology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, P. R. China
| | - Danlei Shen
- Department of Gastroenterology, Wuxi Hospital of Traditional Chinese Medicine, Wuxi, Jiangsu, P. R. China
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Druffner SR, Venkateshwaraprabu S, Khadka S, Duncan BC, Morris MT, Sen-Kilic E, Damron FH, Liechti GW, Busada JT. Comparison of gastric inflammation and metaplasia induced by Helicobacter pylori or Helicobacter felis colonization in mice. Microbiol Spectr 2024; 12:e0001524. [PMID: 38682907 PMCID: PMC11237807 DOI: 10.1128/spectrum.00015-24] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/04/2024] [Accepted: 03/18/2024] [Indexed: 05/01/2024] Open
Abstract
Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Here, we identified the differences in gastric inflammation, atrophy, and metaplasia associated with HP and HF infection in mice. PMSS1 HP strain or the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages revealing that both bacteria exhibit similar immunostimulatory effects in vitro. Next, C57BL/6J mice were infected with HP or HF and were assessed 2 months post-infection. HP-infected mice caused modest inflammation within both the gastric corpus and antrum, and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced the expression of pyloric metaplasia (PM) markers. HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for studies on the effects of gastric inflammation on tumorigenesis. . IMPORTANCE Mouse infection models with Helicobacter species are widely used to study Helicobacter pathogenesis and gastric cancer initiation. However, Helicobacter pylori is not a natural mouse pathogen, and mouse-adapted H. pylori strains are poorly immunogenic. In contrast, Helicobacter felis is a natural mouse pathogen that induces robust gastric inflammation and is often used in mice to investigate gastric cancer initiation. Although both bacterial strains are widely used, their disease pathogenesis in mice differs dramatically. However, few studies have directly compared the pathogenesis of these bacterial species in mice, and the contrasting features of these two models are not clearly defined. This study directly compares the gastric inflammation, atrophy, and metaplasia development triggered by the widely used PMSS1 H. pylori and CS1 H. felis strains in mice. It serves as a useful resource for researchers to select the experimental model best suited for their studies.
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Affiliation(s)
- Sara R. Druffner
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Shrinidhi Venkateshwaraprabu
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Stuti Khadka
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Benjamin C. Duncan
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Maeve T. Morris
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Emel Sen-Kilic
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - Fredrick H. Damron
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
| | - George W. Liechti
- Department of Microbiology and Immunology, Uniformed Services University of the Health Sciences, Bethesda, Maryland, USA
| | - Jonathan T. Busada
- Department of Microbiology, Immunology and Cell Biology, West Virginia University School of Medicine, Morgantown, West Virginia, USA
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15
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Qiao Z, Wang E, Bao B, Tan X, Yuan L, Wang D. Association of Helicobacter pylori CagA seropositivity with gastric precancerous lesions: a systematic review and meta-analysis. Eur J Gastroenterol Hepatol 2024; 36:687-694. [PMID: 38526941 DOI: 10.1097/meg.0000000000002765] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 03/27/2024]
Abstract
The objective of this meta-analysis is to delineate the association between H. pylori CagA serological status and the prevalence of gastric precancerous lesions (GPL). We searched peer-reviewed articles up to October 2023. The extraction of data from the included studies was carried out as well as the quality assessment. Pooled effect sizes were calculated using a random effect model. Thirteen studies met the inclusion criteria, comprising 2728 patients with GPL and 17 612 controls. The aggregate odds ratio (OR) for the association between serum CagA and GPL was 2.74 (95% CI = 2.25-3.32; P = 0.00; I 2 = 60.4%), irrespective of H. pylori infection status. Within the H. pylori -infected cohort, the OR was 2.25 (95% CI = 1.99-2.56; P = 0.00; I 2 = 0.0%). Conversely, among the non-infected individuals, the OR was 1.63 (95% CI = 1.04-2.54; P = 0.038; I 2 = 0.0%). Heterogeneity was explored using subgroup and meta-regression analyses, indicating that the variability between studies likely stemmed from differences in disease classification. Our results demonstrated robustness and negligible publication bias. The meta-analysis underscores a more pronounced association between H. pylori CagA seropositivity and the risk of developing GPL than between seronegativity and the same risk, irrespective of H. pylori infection status at the time. Additionally, the strength of the association was heightened in the presence of an active H. pylori infection. The implications of these findings advocate for the utility of CagA serostatus as a potential biomarker for screening GPL.
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Affiliation(s)
- Zengyun Qiao
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, Dalian
- Dalian Municipal Central Hospital, China Medical University, Shenyang
| | - Enbo Wang
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, Dalian
| | - Boyang Bao
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, Dalian
- Dalian Municipal Central Hospital, Dalian Medical University, Dalian
| | - Xiaodong Tan
- Department of Pancreatic and Thyroid Surgery, Shengjing Hospital of China Medical University, Shenyang, China
| | - Liu Yuan
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, Dalian
- Dalian Municipal Central Hospital, China Medical University, Shenyang
| | - Dong Wang
- Department of Hepatobiliary Surgery, Dalian Municipal Central Hospital, Dalian
- Dalian Municipal Central Hospital, China Medical University, Shenyang
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16
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Wei YF, Li X, Zhao MR, Liu S, Min L, Zhu ST, Zhang ST, Xie SA. Helicobacter pylori disrupts gastric mucosal homeostasis by stimulating macrophages to secrete CCL3. Cell Commun Signal 2024; 22:263. [PMID: 38730482 PMCID: PMC11084090 DOI: 10.1186/s12964-024-01627-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2024] [Accepted: 04/21/2024] [Indexed: 05/12/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is the predominant etiological agent of gastritis and disrupts the integrity of the gastric mucosal barrier through various pathogenic mechanisms. After H. pylori invades the gastric mucosa, it interacts with immune cells in the lamina propria. Macrophages are central players in the inflammatory response, and H. pylori stimulates them to secrete a variety of inflammatory factors, leading to the chronic damage of the gastric mucosa. Therefore, the study aims to explore the mechanism of gastric mucosal injury caused by inflammatory factors secreted by macrophages, which may provide a new mechanism for the development of H. pylori-related gastritis. METHODS The expression and secretion of CCL3 from H. pylori infected macrophages were detected by RT-qPCR, Western blot and ELISA. The effect of H. pylori-infected macrophage culture medium and CCL3 on gastric epithelial cells tight junctions were analyzed by Western blot, immunofluorescence and transepithelial electrical resistance. EdU and apoptotic flow cytometry assays were used to detect cell proliferation and apoptosis levels. Dual-luciferase reporter assays and chromatin immunoprecipitation assays were used to study CCL3 transcription factors. Finally, gastric mucosal tissue inflammation and CCL3 expression were analyzed by hematoxylin and eosin staining and immunohistochemistry. RESULTS After H. pylori infection, CCL3 expressed and secreted from macrophages were increased. H. pylori-infected macrophage culture medium and CCL3 disrupted gastric epithelial cells tight junctions, while CCL3 neutralizing antibody and receptor inhibitor of CCL3 improved the disruption of tight junctions between cells. In addition, H. pylori-infected macrophage culture medium and CCL3 recombinant proteins stimulated P38 phosphorylation, and P38 phosphorylation inhibitor improved the disruption of tight junctions between cells. Besides, it was identified that STAT1 was a transcription factor of CCL3 and H. pylori stimulated macrophage to secret CCL3 through the JAK1-STAT1 pathway. Finally, after mice were injected with murine CCL3 recombinant protein, the gastric mucosal injury and inflammation were aggravated, and the phosphorylation level of P38 was increased. CONCLUSIONS In summary, our findings demonstrate that H. pylori infection stimulates macrophages to secrete CCL3 via the JAK1-STAT1 pathway. Subsequently, CCL3 damages gastric epithelial tight junctions through the phosphorylation of P38. This may be a novel mechanism of gastric mucosal injury in H. pylori-associated gastritis.
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Affiliation(s)
- Yan-Fei Wei
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Xue Li
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
| | - Meng-Ran Zhao
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, State Key Laboratory of Digestive Health, Beijing, 100050, China
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, State Key Laboratory of Digestive Health, Beijing, 100050, China
| | - Li Min
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, State Key Laboratory of Digestive Health, Beijing, 100050, China
| | - Sheng-Tao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, State Key Laboratory of Digestive Health, Beijing, 100050, China
| | - Shu-Tian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
| | - Si-An Xie
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, China.
- National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, State Key Laboratory of Digestive Health, Beijing, 100050, China.
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Kamel M, Aleya S, Alsubih M, Aleya L. Microbiome Dynamics: A Paradigm Shift in Combatting Infectious Diseases. J Pers Med 2024; 14:217. [PMID: 38392650 PMCID: PMC10890469 DOI: 10.3390/jpm14020217] [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: 12/26/2023] [Revised: 02/15/2024] [Accepted: 02/16/2024] [Indexed: 02/24/2024] Open
Abstract
Infectious diseases have long posed a significant threat to global health and require constant innovation in treatment approaches. However, recent groundbreaking research has shed light on a previously overlooked player in the pathogenesis of disease-the human microbiome. This review article addresses the intricate relationship between the microbiome and infectious diseases and unravels its role as a crucial mediator of host-pathogen interactions. We explore the remarkable potential of harnessing this dynamic ecosystem to develop innovative treatment strategies that could revolutionize the management of infectious diseases. By exploring the latest advances and emerging trends, this review aims to provide a new perspective on combating infectious diseases by targeting the microbiome.
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Affiliation(s)
- Mohamed Kamel
- Department of Medicine and Infectious Diseases, Faculty of Veterinary Medicine, Cairo University, Giza 11221, Egypt
| | - Sami Aleya
- Faculty of Medecine, Université de Bourgogne Franche-Comté, Hauts-du-Chazal, 25030 Besançon, France;
| | - Majed Alsubih
- Department of Civil Engineering, King Khalid University, Guraiger, Abha 62529, Saudi Arabia;
| | - Lotfi Aleya
- Laboratoire de Chrono-Environnement, Université de Bourgogne Franche-Comté, UMR CNRS 6249, La Bouloie, 25030 Besançon, France;
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18
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Yang S, Hao S, Ye H, Zhang X. Cross-talk between Helicobacter pylori and gastric cancer: a scientometric analysis. Front Cell Infect Microbiol 2024; 14:1353094. [PMID: 38357448 PMCID: PMC10864449 DOI: 10.3389/fcimb.2024.1353094] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2023] [Accepted: 01/17/2024] [Indexed: 02/16/2024] Open
Abstract
Background Helicobacter pylori (HP) is considered a leading risk factor for gastric cancer (GC). The aim of this article is to conduct bibliometric and visual analysis to assess scientific output, identify highly cited papers, summarize current knowledge, and explore recent hotspots and trends in HP/GC research. Methods A bibliographic search was conducted on October 24, 2023, to retrieve relevant studies on HP/GC research between 2003 and 2022. The search terms were attached to HP and GC. The main data were from the Web of Science Core Collection (WoSCC). Data visualization was performed using Biblioshiny, VOSviewer, and Microsoft Excel. Results In HP/GC research, 1970 papers were retrieved. The total number of papers (Np) in HP/GC was growing from 2003 to 2022. China and Japan were in the leading position and made the most contributions to HP/GC. Vanderbilt University and the US Department of Veterans Affairs had the highest Np. The most productive authors were Peek Jr Richard M. and Piazuelo M Blanca. Helicobacter received the most Np, while Gastroenterology had the most total citations (TC). High-cited publications and keyword clustering were used to identify the current status and trends in HP/GC research, while historical citation analysis provided insight into the evolution of HP/GC research. The hot topics included the effect of HP on gastric tumorigenesis and progression, the pathogenesis of HP-induced GC (HP factors), and the mechanisms by which HP affects GC (host factors). Research in the coming years could focus on topics such as autophagy, gut microbiota, immunotherapy, exosomes, epithelial-mesenchymal transition (EMT), and gamma-glutamyl transpeptidase (GGT). Conclusion This study evaluated the global scientific output in HP/GC research and its quantitative characteristics, identified the essential works, and collected information on the current status, main focuses and emerging trends in HP/GC research to provide academics with guidance for future paths.
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Affiliation(s)
- Shanshan Yang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Shaodong Hao
- Spleen-Stomach Department, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Hui Ye
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
| | - Xuezhi Zhang
- Department of Integrated Traditional Chinese and Western Medicine, Peking University First Hospital, Beijing, China
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19
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Liu T, Chai S, Li M, Chen X, Xie Y, Zhao Z, Xie J, Yu Y, Gao F, Zhu F, Yang L. A nanoparticle-based sonodynamic therapy reduces Helicobacter pylori infection in mouse without disrupting gut microbiota. Nat Commun 2024; 15:844. [PMID: 38286999 PMCID: PMC10825188 DOI: 10.1038/s41467-024-45156-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Accepted: 01/15/2024] [Indexed: 01/31/2024] Open
Abstract
Infection by Helicobacter pylori, a prevalent global pathogen, currently requires antibiotic-based treatments, which often lead to antimicrobial resistance and gut microbiota dysbiosis. Here, we develop a non-antibiotic approach using sonodynamic therapy mediated by a lecithin bilayer-coated poly(lactic-co-glycolic) nanoparticle preloaded with verteporfin, Ver-PLGA@Lecithin, in conjunction with localized ultrasound exposure of a dosage permissible for ultrasound medical devices. This study reveals dual functionality of Ver-PLGA@Lecithin. It effectively neutralizes vacuolating cytotoxin A, a key virulence factor secreted by H. pylori, even in the absence of ultrasound. When coupled with ultrasound exposure, it inactivates H. pylori by generating reactive oxygen species, offering a potential solution to overcome antimicrobial resistance. In female mouse models bearing H. pylori infection, this sonodynamic therapy performs comparably to the standard triple therapy in reducing gastric infection. Significantly, unlike the antibiotic treatments, the sonodynamic therapy does not negatively disrupt gut microbiota, with the only major impact being upregulation of Lactobacillus, which is a bacterium widely used in yogurt products and probiotics. This study presents a promising alternative to the current antibiotic-based therapies for H. pylori infection, offering a reduced risk of antimicrobial resistance and minimal disturbance to the gut microbiota.
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Affiliation(s)
- Tao Liu
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Shuang Chai
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Mingyang Li
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Xu Chen
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yutao Xie
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Zehui Zhao
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Jingjing Xie
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Yunpeng Yu
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Feng Gao
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Feng Zhu
- Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China
| | - Lihua Yang
- Hefei National Research Center for Physical Sciences at the Microscale, University of Science and Technology of China, Hefei, Anhui, 230026, China.
- CAS Key Laboratory of Soft Matter Chemistry, University of Science and Technology of China, Hefei, Anhui, 230026, China.
- School of Chemistry and Materials Science, University of Science and Technology of China, Hefei, Anhui, 230026, China.
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Wei BR, Zhao YJ, Cheng YF, Huang C, Zhang F. Helicobacter pylori infection and Parkinson's Disease: etiology, pathogenesis and levodopa bioavailability. Immun Ageing 2024; 21:1. [PMID: 38166953 PMCID: PMC10759355 DOI: 10.1186/s12979-023-00404-1] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/16/2023] [Accepted: 12/11/2023] [Indexed: 01/05/2024]
Abstract
Parkinson's disease (PD), a neurodegenerative disorder with an unknown etiology, is primarily characterized by the degeneration of dopamine (DA) neurons. The prevalence of PD has experienced a significant surge in recent years. The unidentified etiology poses limitations to the development of effective therapeutic interventions for this condition. Helicobacter pylori (H. pylori) infection has affected approximately half of the global population. Mounting evidences suggest that H. pylori infection plays an important role in PD through various mechanisms. The autotoxin produced by H. pylori induces pro-inflammatory cytokines release, thereby facilitating the occurrence of central inflammation that leads to neuronal damage. Simultaneously, H. pylori disrupts the equilibrium of gastrointestinal microbiota with an overgrowth of bacteria in the small intestinal known as small intestinal bacterial overgrowth (SIBO). This dysbiosis of the gut flora influences the central nervous system (CNS) through microbiome-gut-brain axis. Moreover, SIBO hampers levodopa absorption and affects its therapeutic efficacy in the treatment of PD. Also, H. pylori promotes the production of defensins to regulate the permeability of the blood-brain barrier, facilitating the entry of harmful factors into the CNS. In addition, H. pylori has been found to induce gastroparesis, resulting in a prolonged transit time for levodopa to reach the small intestine. H. pylori may exploit levodopa to facilitate its own growth and proliferation, or it can inflict damage to the gastrointestinal mucosa, leading to gastrointestinal ulcers and impeding levodopa absorption. Here, this review focused on the role of H. pylori infection in PD from etiology, pathogenesis to levodopa bioavailability.
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Affiliation(s)
- Bang-Rong Wei
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yu-Jia Zhao
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Yu-Feng Cheng
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China
| | - Chun Huang
- The Fifth People's Hospital of Chongqing, Chongqing, China
| | - Feng Zhang
- Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education and Key Laboratory of Basic Pharmacology of Guizhou Province and Laboratory Animal Centre, Zunyi Medical University, Zunyi, Guizhou, China.
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21
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Druffner SR, Venkateshwaraprabu S, Khadka S, Duncan BC, Morris MT, Sen-Kilic E, Damron FH, Liechti GW, Busada JT. Comparison of gastric inflammation and metaplasia induced by Helicobacter pylori or Helicobacter felis colonization in mice. BIORXIV : THE PREPRINT SERVER FOR BIOLOGY 2023:2023.12.22.573128. [PMID: 38187587 PMCID: PMC10769338 DOI: 10.1101/2023.12.22.573128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
Background Gastric cancer is the fifth most diagnosed cancer in the world. Infection by the bacteria Helicobacter pylori (HP) is associated with approximately 75% of gastric cancer cases. HP infection induces chronic gastric inflammation, damaging the stomach and fostering carcinogenesis. Most mechanistic studies on Helicobacter- induced gastric cancer initiation are performed in mice and utilize either mouse-adapted strains of HP or the natural mouse pathogen Helicobacter felis (HF). Each of these infection models is associated with strengths and weaknesses. Here, we identified the differences in immunogenicity and gastric pathological changes associated with HP and HF infection in mice. Material and Methods PMSS1 HP strain or with the CS1 HF strain were co-cultured with mouse peritoneal macrophages to assess their immunostimulatory effects. C57BL/6J mice were infected with HP or HF, and gastric inflammation, atrophy, and metaplasia development were assessed 2 months post-infection. Results HP and HF induced similar cytokine production from cultured mouse peritoneal macrophages. HP-infected mice caused modest inflammation within both the gastric corpus and antrum and did not induce significant atrophy within the gastric corpus. In contrast, HF induced significant inflammation throughout the gastric corpus and antrum. Moreover, HF infection was associated with significant atrophy of the chief and parietal cell compartments and induced expression of pyloric metaplasia markers. Conclusions HP is poorly immunogenic compared to HF. HF induces dramatic CD4+ T cell activation, which is associated with increased gastric cancer risk in humans. Thus, HP studies in mice are better suited for studies on colonization, while HF is more strongly suited for pathogenesis and cancer initiation studies.
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22
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Xu JY, Fan JX, Hu M, Zeng J. Microorganism-regulated autophagy in gastrointestinal cancer. PeerJ 2023; 11:e16130. [PMID: 37786582 PMCID: PMC10541808 DOI: 10.7717/peerj.16130] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 08/28/2023] [Indexed: 10/04/2023] Open
Abstract
Gastrointestinal cancer has always been one of the most urgent problems to be solved, and it has become a major global health issue. Microorganisms in the gastrointestinal tract regulate normal physiological and pathological processes. Accumulating evidence reveals the role of the imbalance in the microbial community during tumorigenesis. Autophagy is an important intracellular homeostatic process, where defective proteins and organelles are degraded and recycled under stress. Autophagy plays a dual role in tumors as both tumor suppressor and tumor promoter. Many studies have shown that autophagy plays an important role in response to microbial infection. Here, we provide an overview on the regulation of the autophagy signaling pathway by microorganisms in gastrointestinal cancer.
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Affiliation(s)
- Jun-Yu Xu
- Chongqing Normal University, Chongqing, China
| | | | - Min Hu
- Chongqing Normal University, Chongqing, China
| | - Jun Zeng
- Chongqing Normal University, Chongqing, China
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23
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Fernández-Espejo E. Microorganisms associated with increased risk of Parkinson's disease. Neurologia 2023; 38:495-503. [PMID: 35644845 DOI: 10.1016/j.nrleng.2020.08.023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/03/2020] [Accepted: 08/26/2020] [Indexed: 11/25/2022] Open
Abstract
Parkinson's disease (PD) is a neurodegenerative disorder that affects more than 7 million people worldwide. Its aetiology is unknown, although the hypothesis of a genetic susceptibility to environmental agents is accepted. These environmental agents include fungi, bacteria, and viruses. Three microorganisms are directly associated with a significantly increased risk of developing Parkinson's disease: the fungal genus Malassezia, the bacterium Helicobacter pylori, and the hepatitis C virus. If the host is vulnerable due to genetic susceptibility or immune weakness, these microorganisms can access and infect the nervous system, causing chronic neuroinflammation with neurodegeneration. Other microorganisms show an epidemiological association with the disease, including the influenza type A, Japanese encephalitis type B, St Louis, and West Nile viruses. These viruses can affect the nervous system, causing encephalitis, which can result in parkinsonism. This article reviews the role of all these microorganisms in Parkinson's disease.
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Affiliation(s)
- E Fernández-Espejo
- Laboratorio de Neurología Molecular, Universidad de Sevilla, Sevilla, Spain; Red Andaluza de Investigación Clínica y Traslacional en Neurología (Neuro-RECA), Málaga, Spain.
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24
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Yang HJ. [Gastric Cancer and Gastric Microbiome]. THE KOREAN JOURNAL OF GASTROENTEROLOGY = TAEHAN SOHWAGI HAKHOE CHI 2023; 81:235-242. [PMID: 37350518 DOI: 10.4166/kjg.2023.055] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/15/2023] [Revised: 05/26/2023] [Accepted: 05/26/2023] [Indexed: 06/24/2023]
Abstract
Gastric cancer remains a significant disease burden in Korea, with Helicobacter pylori infections being the most crucial risk factor. With the advent of next-generation sequencing, the role of gastric microbiota in gastric cancer has attracted increasing attention. Studies have shown that the gastric microbiota of patients with gastric cancer differs in composition from that of the controls, with reduced microbial diversity. Lactic acid bacteria and oral microflora are often enriched in gastric cancer and are believed to induce chronic inflammation or promote the production of nitroso compounds. This review focuses on recent studies comparing the gastric microbiome in gastric cancer patients and controls.
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Affiliation(s)
- Hyo-Joon Yang
- Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea
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25
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Ghosh N, Kesh K, Singh PK, Sharma U, Chupikova I, Ramakrishnan S, Roy S. Morphine use induces gastric microbial dysbiosis driving gastric inflammation through TLR2 signalling which is attenuated by proton pump inhibition. Br J Pharmacol 2023; 180:1582-1596. [PMID: 36585367 PMCID: PMC10175111 DOI: 10.1111/bph.16025] [Citation(s) in RCA: 9] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2022] [Revised: 09/29/2022] [Accepted: 10/28/2022] [Indexed: 01/01/2023] Open
Abstract
BACKGROUND AND PURPOSE Opioids are the standard drug for pain management; however, their effects on gastric dysfunction are relatively understudied. Opioid users have a higher incidence of gastric pathology leading to increased hospitalization. Herein, we investigated the consequences of morphine use on gastric pathology and the underlying mechanisms. We further investigated the therapeutic benefit of proton pump inhibition to overcome morphine-mediated gastric inflammation. EXPERIMENTAL APPROACH Mice were implanted with 25 mg slow-release morphine and placebo pellets. Gastric microbiome analyses were performed. Gastric damage was assayed. Gastric pH was measured. Germ-free and TLR2KO mice were used to investigate the mechanisms. Gastroprotective studies were performed with the proton pump inhibitor (PPI) omeprazole. KEY RESULTS Chronic morphine treatment alters gastric microbial composition and induces preferential expansion of pathogenic bacterial communities such as Streptococcus and Pseudomonas. Morphine causes disruption of the gastric mucosal layer, increases apoptosis, and elevates inflammatory cytokines. Moreover, morphine-mediated gastric pathology was significantly attenuated in germ-free mice, and reconstitution of morphine gastric microbiome in germ-free mice resulted gastric inflammation. In addition, morphine-mediated gastric inflammation was attenuated in TLR2KO mice. Morphine causes a decrease in gastric pH, which contributes to gastric dysbiosis leads to gastric inflammation. Omeprazole treatment inhibits gastric acidity, rescuing morphine-induced gastric dysbiosis and preventing inflammation. CONCLUSION AND IMPLICATIONS This study attributes morphine-induced gastric acidity as a driver of gastric dysbiosis and pathology and proposes the therapeutic use of PPI as an inexpensive approach for the clinical management of morphine-associated pathophysiology.
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Affiliation(s)
- Nillu Ghosh
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Kousik Kesh
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Praveen Kumar Singh
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Umakant Sharma
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Irina Chupikova
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
| | - Sundaram Ramakrishnan
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
| | - Sabita Roy
- Department of Surgery, Miller School of Medicine, University of Miami, Miami, FL, USA
- Sylvester Comprehensive Cancer Center, Miami, FL, USA
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26
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Adejumo AC, Labonte P, Bukong TN. Relationship Between Recreational Cannabis Use and Helicobacter pylori Infection. Cannabis Cannabinoid Res 2023; 8:537-546. [PMID: 34748370 PMCID: PMC10249739 DOI: 10.1089/can.2021.0139] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Background: Cannabis plant extracts suppress gastric acid secretion and inflammation, and promote gastroduodenal ulcer healing, all of which are triggered by Helicobacter Pylori infection (HPI). Here, we evaluate the association between cannabis use and HPI among a representative community sample. Materials and Methods: We identified respondents who completed cannabis use questions and were tested for HPI (H. pylori IgG antibody seropositivity) from the National Health and Nutrition Examination Survey III dataset (n=4556). Cannabis usage was categorized as ever-use (ever, never), cumulative lifetime use (>10-times, 1-10-times, never), or recent use (>31-days-ago, within-31-days, never). We calculated the crude and adjusted risk (prevalence rate ratio, cPRR and aPRR) of having HPI with cannabis use using generalized Poisson models (SAS 9.4). The models were adjusted for demographics and risk factors for HPI. Results: The prevalence of HPI was lower among ever versus never cannabis users (18.6% vs. 33%, p<0.0001). Cannabis use was associated with a decreased risk of HPI (cPRR: 0.56 confidence interval [95% CI: 0.47-0.67]; p<0.0001), which persisted after adjusting for demographics (aPRR: 0.75 [95% CI: 0.63-0.90]; p=0.0016) and comorbidities (aPRR: 0.79 [95% CI: 0.66-0.95]; p=0.0145). Further, individuals with >10-times lifetime cannabis use had a decreased risk of HPI compared with those with 1-10-times lifetime use (aPRR: 0.70 [95% CI: 0.55-0.89]; p=0.0011) and never-users (aPRR: 0.65 [95% CI: 0.50-0.84]; p=0.0002). Conclusion: Recreational cannabis use is associated with diminished risk of HPI. These observations suggest the need for additional research assessing the effects of medical cannabis formulations on HPI.
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Affiliation(s)
- Adeyinka Charles Adejumo
- Division of Gastroenterology, Hepatology, and Nutrition, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
| | - Patrick Labonte
- Armand-Frappier Santé Biotechnologie Research Centre-INRS, Laval, Québec, Canada
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Zhou B, Szymanski CM, Baylink A. Bacterial chemotaxis in human diseases. Trends Microbiol 2023; 31:453-467. [PMID: 36411201 PMCID: PMC11238666 DOI: 10.1016/j.tim.2022.10.007] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2022] [Revised: 10/16/2022] [Accepted: 10/18/2022] [Indexed: 11/21/2022]
Abstract
To infect and cause disease, bacterial pathogens must localize to specific regions of the host where they possess the metabolic and defensive acumen for survival. Motile flagellated pathogens exercise control over their localization through chemotaxis to direct motility based on the landscape of exogenous nutrients, toxins, and molecular cues sensed within the host. Here, we review advances in understanding the roles chemotaxis plays in human diseases. Chemotaxis drives pathogen colonization to sites of inflammation and injury and mediates fitness advantages through accessing host-derived nutrients from damaged tissue. Injury tropism may worsen clinical outcomes through instigating chronic inflammation and subsequent cancer development. Inhibiting bacterial chemotactic systems could act synergistically with antibacterial medicines for more effective and specific eradication.
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Affiliation(s)
- Bibi Zhou
- University of Georgia, Department of Microbiology and Complex Carbohydrate Research Center, Athens, GA 30602, USA
| | - Christine M Szymanski
- University of Georgia, Department of Microbiology and Complex Carbohydrate Research Center, Athens, GA 30602, USA
| | - Arden Baylink
- Washington State University, Department of Veterinary Microbiology and Pathology, Pullman, WA 99164, USA.
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28
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Ait-Zenati F, Djoudi F, Mehelleb D, Madaoui M. Involvement of the human microbiome in frequent cancers, current knowledge and carcinogenesis mechanisms. Bull Cancer 2023:S0007-4551(23)00092-9. [PMID: 36959041 DOI: 10.1016/j.bulcan.2023.01.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 01/10/2023] [Accepted: 01/31/2023] [Indexed: 03/25/2023]
Abstract
The human body is home to a complex microbial community, living in symbiosis. However, when an imbalance occurs, known as dysbiosis, it can lead to organic diseases such as cancers. Helicobacter pylori is commonly recognized as the causative agent of gastric cancer. Numerous studies have explored the potential role of other microorganisms in cancers. For example, the role of intestinal microbiota in the hepatocellular carcinoma formation and progression, the microbiota in breast cancer and the interaction between the microbiome and TP53 in human lung carcinogenesis. In this review, we highlight the latest findings on the microbiome involved in the most common cancers and the suggested mechanisms of carcinogenesis.
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Affiliation(s)
- Fazia Ait-Zenati
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
| | - Ferhat Djoudi
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria.
| | - Dalila Mehelleb
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
| | - Menad Madaoui
- Laboratoire d'écologie microbienne, département de microbiologie, université de Bejaia, route de Targa-Ouzemour, Bejaia, Algeria
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29
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Niikura R, Hayakawa Y, Nagata N, Miyoshi-Akiayama T, Miyabayashi K, Tsuboi M, Suzuki N, Hata M, Arai J, Kurokawa K, Abe S, Uekura C, Miyoshi K, Ihara S, Hirata Y, Yamada A, Fujiwara H, Ushiku T, Woods SL, Worthley DL, Hatakeyama M, Han YW, Wang TC, Kawai T, Fujishiro M. Non- Helicobacter pylori Gastric Microbiome Modulates Prooncogenic Responses and Is Associated With Gastric Cancer Risk. GASTRO HEP ADVANCES 2023; 2:684-700. [PMID: 39129877 PMCID: PMC11307406 DOI: 10.1016/j.gastha.2023.03.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/03/2022] [Accepted: 03/08/2023] [Indexed: 08/13/2024]
Abstract
Background and Aims Although Helicobacter pylori is the most important bacterial carcinogen in gastric cancer (GC), GC can emerge even after H. pylori eradication. Studies suggest that various constituents of the gastric microbiome may influence GC development, but the role of individual pathogens is unclear. Methods Human gastric mucosal samples were analyzed by 16SrRNA sequencing to investigate microbiome composition and its association with clinical parameters, including GC risk. Identified bacteria in the stomach were cocultured with gastric epithelial cells or inoculated into mice, and transcriptomic changes, DNA damage, and inflammation were analyzed. Bacterial reads in GC tissues were examined together with transcriptomic and genetic sequencing data in the cancer genome atlas dataset. Results Patients after Helicobacter pylori eradication formed 3 subgroups based on the microbial composition revealed by 16SrRNA sequencing. One dysbiotic group enriched with Fusobacterium and Neisseria species was associated with a significantly higher GC incidence. These species activated prooncogenic pathways in gastric epithelial cells and promoted inflammation in mouse stomachs. Sugar chains that constitute gastric mucin attenuate host-bacteria interactions. Metabolites from Fusobacterium species were genotoxic, and the presence of the bacteria was associated with an inflammatory signature and a higher tumor mutation burden. Conclusion Gastric microbiota in the dysbiotic stomach is associated with GC development after H. pylori eradication and plays a pathogenic role through direct host-bacteria interaction.
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Affiliation(s)
- Ryota Niikura
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
- Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Yoku Hayakawa
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Naoyoshi Nagata
- Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Tohru Miyoshi-Akiayama
- Pathogenic Microbe Laboratory, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan
| | - Koji Miyabayashi
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Mayo Tsuboi
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Nobumi Suzuki
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Masahiro Hata
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Junya Arai
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Ken Kurokawa
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Sohei Abe
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Chie Uekura
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Kotaro Miyoshi
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Sozaburo Ihara
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Yoshihiro Hirata
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Atsuo Yamada
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Hiroaki Fujiwara
- Department of Gastroenterology, The Institute for Medical Science, Asahi-life Foundation, Tokyo, Japan
| | - Tetsuo Ushiku
- Department of Pathology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
| | - Susan L. Woods
- Cancer Theme, SAHMRI, Adelaide, South Australia, Australia
- Medical Specialties, Medical School, The University of Adelaide, Adelaide, South Australia, Australia
| | | | - Masanori Hatakeyama
- Department of Microbiology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan
| | - Yiping W. Han
- Division of Digestive and Liver Disease, Department of Medicine, Columbia University, New York, New York
- Department of Microbiology and Immunology, Vagelos College of Physicians & Surgeons, Columbia University, New York, New York
- Section of Oral, Diagnostic and Rehabilitation Sciences, College of Dental Medicine, Columbia University, New York, New York
| | - Timothy C. Wang
- Division of Digestive and Liver Disease, Department of Medicine, Columbia University, New York, New York
| | - Takashi Kawai
- Gastroenterological Endoscopy, Tokyo Medical University, Tokyo, Japan
| | - Mitsuhiro Fujishiro
- Department of Gastroenterology, Graduate school of medicine, The University of Tokyo, Tokyo, Japan
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Ser HL, Au Yong SJ, Shafiee MN, Mokhtar NM, Ali RAR. Current Updates on the Role of Microbiome in Endometriosis: A Narrative Review. Microorganisms 2023; 11:360. [PMID: 36838325 PMCID: PMC9962481 DOI: 10.3390/microorganisms11020360] [Citation(s) in RCA: 13] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2022] [Revised: 01/16/2023] [Accepted: 01/25/2023] [Indexed: 02/04/2023] Open
Abstract
Endometriosis affects approximately 6 to 10% of reproductive-age women globally. Despite much effort invested, the pathogenesis that promotes the development, as well as the progression of this chronic inflammatory disease, is poorly understood. The imbalance in the microbiome or dysbiosis has been implicated in a variety of human diseases, especially the gut microbiome. In the case of endometriosis, emerging evidence suggests that there may be urogenital-gastrointestinal crosstalk that leads to the development of endometriosis. Researchers may now exploit important information from microbiome studies to design endometriosis treatment strategies and disease biomarkers with the use of advanced molecular technologies and increased computational capacity. Future studies into the functional profile of the microbiome would greatly assist in the development of microbiome-based therapies to alleviate endometriosis symptoms and improve the quality of life of women suffering from endometriosis.
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Affiliation(s)
- Hooi-Leng Ser
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia
| | - Siu-Jung Au Yong
- Department of Biological Sciences, School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia
| | - Mohamad Nasir Shafiee
- Department of Obstetrics and Gynaecology, Faculty of Medicine, Universiti Kebangsan Malaysia, Cheras 56000, Malaysia
| | - Norfilza Mohd Mokhtar
- Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia
| | - Raja Affendi Raja Ali
- School of Medical and Life Sciences, Sunway University, Bandar Sunway 47500, Malaysia
- Gut Research Group, Faculty of Medicine, Universiti Kebangsan Malaysia, Cheras 56000, Malaysia
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Guo Y, Cao XS, Zhou MG, Yu B. Gastric microbiota in gastric cancer: Different roles of Helicobacter pylori and other microbes. Front Cell Infect Microbiol 2023; 12:1105811. [PMID: 36704105 PMCID: PMC9871904 DOI: 10.3389/fcimb.2022.1105811] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 12/21/2022] [Indexed: 01/12/2023] Open
Abstract
Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. The gastric microbiota plays a critical role in the development of GC. First, Helicobacter pylori (H. pylori) infection is considered a major risk factor for GC. However, recent studies based on microbiota sequencing technology have found that non-H. pylori microbes also exert effects on gastric carcinogenesis. Following the infection of H. pylori, gastric microbiota dysbiosis could be observed; the stomach is dominated by H. pylori and the abundances of non-H. pylori microbes reduce substantially. Additionally, decreased microbial diversity, alterations in the microbial community structure, negative interactions between H. pylori and other microbes, etc. occur, as well. With the progression of gastric lesions, the number of H. pylori decreases and the number of non-H. pylori microbes increases correspondingly. Notably, H. pylori and non-H. pylori microbes show different roles in different stages of gastric carcinogenesis. In the present mini-review, we provide an overview of the recent findings regarding the role of the gastric microbiota, including the H. pylori and non-H. pylori microbes, in the development of GC.
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Affiliation(s)
- Yang Guo
- Department of Dermatology, Institute of Dermatology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
| | - Xue-Shan Cao
- College of Life Science and Oceanography, Shenzhen University, Shenzhen, China
| | - Meng-Ge Zhou
- Department of Epidemiology and Biostatistics, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, China
| | - Bo Yu
- Department of Dermatology, Institute of Dermatology, Peking University Shenzhen Hospital, Shenzhen Peking University-The Hong Kong University of Science and Technology Medical Center, Shenzhen, China
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Wang Z, Shao SL, Xu XH, Zhao X, Wang MY, Chen A, Cong HY. Helicobacter pylori and gastric microbiota homeostasis: progress and prospects. Future Microbiol 2023; 18:137-157. [PMID: 36688318 DOI: 10.2217/fmb-2022-0102] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/24/2023] Open
Abstract
Helicobacter pylori, a Gram-negative microaerobic bacteria belonging to the phylum Proteobacteria, can colonize in the stomach and duodenum, and cause a series of gastrointestinal diseases such as gastritis, gastric ulcer and even gastric cancer. At present, the high diversity of the microorganisms in the stomach has been confirmed with culture-independent methods; some researchers have also studied the stomach microbiota composition at different stages of H. pylori carcinogenesis. Here, we mainly review the possible role of H. pylori-mediated microbiota changes in the occurrence and development of gastric cancer to provide new ideas for preventing H. pylori infection and regulating microecological imbalance.
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Affiliation(s)
- Zan Wang
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China
| | - Shu-Li Shao
- Department of Central Lab, Weihai Municipal Hospital. Weihai, Shandong, 264200, People's Republic of China
| | - Xiao-Han Xu
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China
| | - Xue Zhao
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China
| | - Ming-Yi Wang
- Department of Central Lab, Weihai Municipal Hospital. Weihai, Shandong, 264200, People's Republic of China
| | - Ai Chen
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China.,Department of Central Lab, Weihai Municipal Hospital. Weihai, Shandong, 264200, People's Republic of China
| | - Hai-Yan Cong
- School of Medical Laboratory, Weifang Medical University, Weifang, Shandong, 261053, People's Republic of China.,Department of Central Lab, Weihai Municipal Hospital. Weihai, Shandong, 264200, People's Republic of China
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Mannion A, Sheh A, Shen Z, Dzink-Fox J, Piazuelo MB, Wilson KT, Peek R, Fox JG. Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America. Gut Microbes 2023; 15:2186677. [PMID: 36907988 PMCID: PMC10026914 DOI: 10.1080/19490976.2023.2186677] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 02/27/2023] [Indexed: 03/14/2023] Open
Abstract
Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.
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Affiliation(s)
- Anthony Mannion
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Alexander Sheh
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Zeli Shen
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - JoAnn Dzink-Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - M. Blanca Piazuelo
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Keith T Wilson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Richard Peek
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - James G. Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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Yu C, Qiu J, Xiong M, Ou C, Zeng M, Song H. Trends in Helicobacter pylori-related gastric ulcer research from 2012 to 2022: A bibliometric and visual analysis. Front Med (Lausanne) 2022; 9:1027534. [PMID: 36507534 PMCID: PMC9726869 DOI: 10.3389/fmed.2022.1027534] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2022] [Accepted: 11/03/2022] [Indexed: 11/24/2022] Open
Abstract
Background Helicobacter pylori-related gastric ulcer (H. pylori-related GU) is one of the most common digestive system diseases that have received widespread attention from researchers. The purpose of this article was to analyze the research status and hotspots of H. pylori-related GU and to predict its future research directions. Methods The article and review papers associated with H. pylori-related GU published from 2012 to 2022 were retrieved from the Web of Science Core Collection (WoSCC). The analysis of knowledge maps and bibliometrics was done with CiteSpace 6.1.R2 Basic and VOSviewer 1.6.18. Results A total of 2,971 articles were included in the study. Between 2012 and 2022, the number of papers published showed an increasing trend. China was the most prolific country, and the United States was the most influential country. Baylor College of Medicine had the largest number of publications and citations among publishing agencies. World Journal of Gastroenterology published the most articles on the H. pylori-related GU field, and GUT was the journal with the most cited articles. Yamaoka Y from Japan was the most productive author, and Graham DY from the USA was the most influential author. A keyword and reference analysis showed that the hot topics of research were the mechanism of H. pylori and the treatment of H. pylori-related GU. The keywords that emerged in the recent 5 years were oxidative stress, probiotics, competitive acid blocker, vonoprazan, gut microbiota, and neutrophil-activating protein. Conclusion Over the recent 10 years, research on H. pylori-related GU has generally shown an increasing trend. The treatment and pathogenesis of H. pylori-related GU remain a hot topic of research. The treatment of H. pylori by oxidative stress and competitive acid inhibitor mechanisms, the influence of gastrointestinal flora on H. pylori, probiotic adjuvant therapy of H. pylori-related GU, and the immunoprotective effect of neutrophil activator protein could be popular research directions and trends in the future.
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Affiliation(s)
- Chang Yu
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Jingyue Qiu
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meng Xiong
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Chen Ou
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Meiyan Zeng
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China
| | - Houpan Song
- Hunan Provincial Key Laboratory of Diagnostic Research in Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,College of Traditional Chinese Medicine, Hunan University of Chinese Medicine, Changsha, Hunan, China,*Correspondence: Houpan Song,
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35
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Gut Microbiota Host-Gene Interaction. Int J Mol Sci 2022; 23:ijms232213717. [PMID: 36430197 PMCID: PMC9698405 DOI: 10.3390/ijms232213717] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2022] [Revised: 10/28/2022] [Accepted: 11/07/2022] [Indexed: 11/09/2022] Open
Abstract
Studies carried out in the last ten years have shown that the metabolites made up from the gut microbiota are essential for multiple functions, such as the correct development of the immune system of newborns, interception of pathogens, and nutritional enrichment of the diet. Therefore, it is not surprising that alteration of the gut microbiota is the starting point of gastrointestinal infection, obesity, type 2 diabetes, inflammatory bowel disease, colorectal cancer, and lung cancer. Diet changes and antibiotics are the major factors damaging the gut microbiota. Early exposure of the newborns to antibiotics may prevent their correct development of the immune system, exposing them to pathogen infections, allergies, and chronic inflammatory diseases. We already know much on how host genes, microbiota, and the environment interact, owing to experiments in several model animals, especially in mice; advances in molecular technology; microbiota transplantation; and comparative metagenomic analysis. However, much more remains to be known. Longitudinal studies on patients undergoing to therapy, along with the identification of bacteria prevalent in responding patients may provide valuable data for improving therapies.
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36
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Zhang J, Xie Q, Huo X, Liu Z, Da M, Yuan M, Zhao Y, Shen G. Impact of intestinal dysbiosis on breast cancer metastasis and progression. Front Oncol 2022; 12:1037831. [PMID: 36419880 PMCID: PMC9678367 DOI: 10.3389/fonc.2022.1037831] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2022] [Accepted: 10/19/2022] [Indexed: 07/30/2023] Open
Abstract
Breast cancer has a high mortality rate among malignant tumors, with metastases identified as the main cause of the high mortality. Dysbiosis of the gut microbiota has become a key factor in the development, treatment, and prognosis of breast cancer. The many microorganisms that make up the gut flora have a symbiotic relationship with their host and, through the regulation of host immune responses and metabolic pathways, are involved in important physiologic activities in the human body, posing a significant risk to health. In this review, we build on the interactions between breast tissue (including tumor tissue, tissue adjacent to the tumor, and samples from healthy women) and the microbiota, then explore factors associated with metastatic breast cancer and dysbiosis of the gut flora from multiple perspectives, including enterotoxigenic Bacteroides fragilis, antibiotic use, changes in gut microbial metabolites, changes in the balance of the probiotic environment and diet. These factors highlight the existence of a complex relationship between host-breast cancer progression-gut flora. Suggesting that gut flora dysbiosis may be a host-intrinsic factor affecting breast cancer metastasis and progression not only informs our understanding of the role of microbiota dysbiosis in breast cancer development and metastasis, but also the importance of balancing gut flora dysbiosis and clinical practice.
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Affiliation(s)
| | | | | | | | | | | | | | - Guoshuang Shen
- Affiliated Hospital of Qinghai University, Affiliated Cancer Hospital of Qinghai University, Xining, China
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Navashenaq JG, Shabgah AG, Banach M, Jamialahmadi T, Penson PE, Johnston TP, Sahebkar A. The interaction of Helicobacter pylori with cancer immunomodulatory stromal cells: New insight into gastric cancer pathogenesis. Semin Cancer Biol 2022; 86:951-959. [PMID: 34600095 DOI: 10.1016/j.semcancer.2021.09.014] [Citation(s) in RCA: 34] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Revised: 09/20/2021] [Accepted: 09/26/2021] [Indexed: 01/27/2023]
Abstract
Gastric cancer is the fourth most common cause of cancer-linked deaths in the world. Gastric tumor cells have biological characteristics such as rapid proliferation, high invasiveness, and drug resistance, which result in recurrence and poor survival. Helicobacter pylori (H. pylori) has been proposed as a first-class carcinogen for gastric cancer according to the 1994 world health organization (WHO) classification. One of the important mechanisms by which H. pylori affects the gastric environment and promotes carcinogenesis is triggering inflammation. H. pylori induces an inflammatory response and a plethora of different signal transduction processes, leading to gastric mucosal disturbance, chronic gastritis, and a multi-step complex pathway that initiates carcinogenesis. It seems undeniable that the interaction between various cell types, including immune cells, gastric epithelium, glands, and stem cells, is vital for the progression and development of carcinogenesis concerning H. pylori. The interactions of H. pylori with surrounding cells play a key role in cancer progression. In this review, we discuss the interplay between H. pylori and tumor-supportive cells, including mesenchymal stem cells (MSCs), cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), and myeloid derived-suppressor cells (MDSCs) in gastric cancer. It is hoped that clarifying the specific mechanisms for 'cross-talk' between H. pylori and these cells will provide promising strategies for developing new treatments.
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Affiliation(s)
| | | | - Maciej Banach
- Department of Hypertension, Chair of Nephrology and Hypertension, Medical University of Lodz, Poland; Polish Mother's Memorial Hospital Research Institute (PMMHRI), Lodz, Poland.
| | - Tannaz Jamialahmadi
- Department of Food Science and Technology, Quchan Branch, Islamic Azad University, Quchan, Iran; Department of Nutrition, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Peter E Penson
- School of Pharmacy and Biomolecular Sciences, Liverpool John Moores University, Liverpool, UK; Liverpool Centre for Cardiovascular Science, Liverpool, UK
| | - Thomas P Johnston
- Division of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, Kansas City, MO, USA
| | - Amirhossein Sahebkar
- Biotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran; Applied Biomedical Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; School of Medicine, The University of Western Australia, Perth, Australia; School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
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Kashyap S, Pal S, Chandan G, Saini V, Chakrabarti S, Saini NK, Mittal A, Thakur VK, Saini AK, Saini RV. Understanding the cross-talk between human microbiota and gastrointestinal cancer for developing potential diagnostic and prognostic biomarkers. Semin Cancer Biol 2022; 86:643-651. [PMID: 33971261 DOI: 10.1016/j.semcancer.2021.04.020] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/31/2021] [Revised: 04/19/2021] [Accepted: 04/29/2021] [Indexed: 02/07/2023]
Abstract
The interaction between gut microbes and gastrointestinal (GI) tract carcinogenesis has always attracted researchers' attention to identify therapeutic targets or potential prognostic biomarkers. Various studies have suggested that the microbiota do show inflammation and immune dysregulation, which led to carcinogenesis in GI tract. In this review, we have focused on the role of microbes present in the gut, intestine, or faeces in GI tract cancers, including esophageal cancer, gastric cancer, and colorectal cancer. Herein, we have discussed the importance of the microbes and their metabolites, which could serve as diagnostic biomarkers for cancer detection, especially in the early stage, and prognostic markers. To maximize the effect of the treatment strategies, an accurate evaluation of the prognosis is imperative for clinicians. There is a vast difference in the microbiota profiles within a population and across the populations depending upon age, diet, lifestyle, genetic makeup, use of antibiotics, and environmental factors. Therefore, the diagnostic efficiency of the microbial markers needs to be further validated. A deeper understanding of the GI cancer and the host microbiota is needed to acquire pivotal information about disease status.
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Affiliation(s)
- Sheetal Kashyap
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India
| | - Soumya Pal
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India
| | - Gourav Chandan
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Vipin Saini
- Maharishi Markandeshwar University, Solan, 173229, Himachal Pradesh, India
| | - Sasanka Chakrabarti
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Neeraj K Saini
- Department of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India
| | - Amit Mittal
- Central Research Cell, MM Institute of Medical Sciences & Research, Maharishi Markandeshwar (Deemed to be University), Mullana, 133207, Haryana, India
| | - Vijay Kumar Thakur
- Biorefining and Advanced Materials Research Center, Scotland's Rural College (SRUC), Kings Buildings, Edinburgh, EH9 3JG, UK
| | - Adesh K Saini
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India.
| | - Reena V Saini
- Department of Biotechnology, MMEC, Maharishi Markandeshwar (Deemed to be University), Mullana-Ambala, 133207, Haryana, India.
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Gut Microbiota Dysbiosis in the Development and Progression of Gastric Cancer. JOURNAL OF ONCOLOGY 2022; 2022:9971619. [PMID: 36072968 PMCID: PMC9441395 DOI: 10.1155/2022/9971619] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/04/2022] [Accepted: 07/29/2022] [Indexed: 12/12/2022]
Abstract
Objectives This study aims to explore gut microbiota dysbiosis in the histological stages of gastric cancer (GC). Methods Feces samples and clinical characteristics were collected from patients with different stages of GC, including 15 superficial gastritis (SG), 13 atrophic gastritis (AG), 8 gastric mucosal atypical hyperplasia (GMAH), and 15 advanced GC cases. The diversity and composition of gut microbiota among the four groups were determined by sequencing the V4 region of bacterial 16S rRNA genes. Results Reduced gut microbial alpha diversity and altered dissimilarity of the microbial community structure were found among the four groups. In addition, 18 species, 6 species, 6 species, and 16 species of bacteria were enriched in the SG, AG, GMAH, and GC groups, respectively, using the linear discriminant analysis (LDA) effect size (LEfSe) analyses. Besides, we found that two new genera, Scardovia and Halomonas, are associated with GC and the metabolic pathways of Genetic information processing and Circulatory System were more abundant in the GC group compared with noncancer groups. Conclusions We identified differences in microbial compositional changes across stages of GC. Six genera and two metabolic pathways were more abundant in the GC group than noncancer groups, suggesting that these findings may contribute to the therapy strategies in GC in the near feature.
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40
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Aziz S, Rasheed F, Akhter TS, Zahra R, König S. Microbial Proteins in Stomach Biopsies Associated with Gastritis, Ulcer, and Gastric Cancer. Molecules 2022; 27:molecules27175410. [PMID: 36080177 PMCID: PMC9458002 DOI: 10.3390/molecules27175410] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/23/2022] [Revised: 08/12/2022] [Accepted: 08/20/2022] [Indexed: 11/24/2022] Open
Abstract
(1) Background: Gastric cancer (GC) is the fourth leading cause of cancer-related deaths worldwide. Helicobacter pylori infection is a major risk factor, but other microbial species may also be involved. In the context of an earlier proteomics study of serum and biopsies of patients with gastroduodenal diseases, we explored here a simplified microbiome in these biopsies (H. pylori, Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Bacteroides fragilis) on the protein level. (2) Methods: A cohort of 75 patients was divided into groups with respect to the findings of the normal gastric mucosa (NGM) and gastroduodenal disorders such as gastritis, ulcer, and gastric cancer (GC). The H. pylori infection status was determined. The protein expression analysis of the biopsy samples was carried out using high-definition mass spectrometry of the tryptic digest (label-free data-independent quantification and statistical analysis). (3) Results: The total of 304 bacterial protein matches were detected based on two or more peptide hits. Significantly regulated microbial proteins like virulence factor type IV secretion system protein CagE from H. pylori were found with more abundance in gastritis than in GC or NGM. This finding could reflect the increased microbial involvement in mucosa inflammation in line with current hypotheses. Abundant proteins across species were heat shock proteins and elongation factors. (4) Conclusions: Next to the bulk of human proteins, a number of species-specific bacterial proteins were detected in stomach biopsies of patients with gastroduodenal diseases, some of which, like those expressed by the cag pathogenicity island, may provide gateways to disease prevention without antibacterial intervention in order to reduce antibiotic resistance.
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Affiliation(s)
- Shahid Aziz
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad 44000, Pakistan
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
- IZKF Core Unit Proteomics, University of Münster, 48149 Münster, Germany
- Correspondence: or
| | - Faisal Rasheed
- Patients Diagnostic Lab, Isotope Application Division, Pakistan Institute of Nuclear Science and Technology (PINSTECH), Islamabad 44000, Pakistan
| | - Tayyab Saeed Akhter
- The Centre for Liver and Digestive Diseases, Holy Family Hospital, Rawalpindi 46300, Pakistan
| | - Rabaab Zahra
- Department of Microbiology, Faculty of Biological Sciences, Quaid-i-Azam University, Islamabad 45320, Pakistan
| | - Simone König
- IZKF Core Unit Proteomics, University of Münster, 48149 Münster, Germany
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Fakharian F, Asgari B, Nabavi-Rad A, Sadeghi A, Soleimani N, Yadegar A, Zali MR. The interplay between Helicobacter pylori and the gut microbiota: An emerging driver influencing the immune system homeostasis and gastric carcinogenesis. Front Cell Infect Microbiol 2022; 12:953718. [PMID: 36046747 PMCID: PMC9423097 DOI: 10.3389/fcimb.2022.953718] [Citation(s) in RCA: 25] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2022] [Accepted: 07/25/2022] [Indexed: 01/06/2023] Open
Abstract
The human gut microbiota are critical for preserving the health status because they are required for digestion and nutrient acquisition, the development of the immune system, and energy metabolism. The gut microbial composition is greatly influenced by the colonization of the recalcitrant pathogen Helicobacter pylori (H. pylori) and the conventional antibiotic regimens that follow. H. pylori is considered to be the main microorganism in gastric carcinogenesis, and it appears to be required for the early stages of the process. However, a non-H. pylori microbiota profile is also suggested, primarily in the later stages of tumorigenesis. On the other hand, specific groups of gut microbes may produce beneficial byproducts such as short-chain fatty acids (acetate, butyrate, and propionate) that can modulate inflammation and tumorigenesis pathways. In this review, we aim to present how H. pylori influences the population of the gut microbiota to modify the host immunity and trigger the development of gastric carcinogenesis. We will also highlight the effect of the gut microbiota on immunotherapeutic approaches such as immune checkpoint blockade in cancer treatment to present a perspective for further development of innovative therapeutic paradigms to prevent the progression of H. pylori-induced stomach cancer.
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Affiliation(s)
- Farzaneh Fakharian
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Behnoush Asgari
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Amir Sadeghi
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Neda Soleimani
- Department of Microbiology, Faculty of Biological Sciences and Technology, Shahid Beheshti University, Tehran, Iran
| | - Abbas Yadegar
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mohammad Reza Zali
- Gastroenterology and Liver Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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42
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Sheng S, Zhao S, Zhang F. Insights into the roles of bacterial infection and antibiotics in Parkinson’s disease. Front Cell Infect Microbiol 2022; 12:939085. [PMID: 35967873 PMCID: PMC9366083 DOI: 10.3389/fcimb.2022.939085] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2022] [Accepted: 07/11/2022] [Indexed: 11/25/2022] Open
Abstract
Parkinson’s disease (PD) is one of the most common neurodegenerative disorders, which is accompanied with the classical motor symptoms and a range of non-motor symptoms. Bacterial infection affects the neuroinflammation associated with the pathology of PD and various antibiotics have also been confirmed to play an important role not only in bacterial infection, but also in the PD progression. This mini-review summarized the role of common bacterial infection in PD and introduced several antibiotics that had anti-PD effects.
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Affiliation(s)
- Shuo Sheng
- Key Laboratory of Basic Pharmacology of the Ministry of Education, Zunyi Medical University, Zunyi, China
- Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, Zunyi Medical University, Zunyi, China
- Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi, China
| | - Shuo Zhao
- Electron Microscopy Room of School of Basic Medicine, Zunyi Medical University, Zunyi, China
| | - Feng Zhang
- Key Laboratory of Basic Pharmacology of the Ministry of Education, Zunyi Medical University, Zunyi, China
- Joint International Research Laboratory of Ethnomedicine of the Ministry of Education, Zunyi Medical University, Zunyi, China
- Key Laboratory of Basic Pharmacology of Guizhou Province, Zunyi Medical University, Zunyi, China
- Laboratory Animal Center, Zunyi Medical University, Zunyi, China
- *Correspondence: Feng Zhang,
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43
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Kwon SK, Park JC, Kim KH, Yoon J, Cho Y, Lee B, Lee JJ, Jeong H, Oh Y, Kim SH, Lee SD, Hwang BR, Chung Y, Kim JF, Nam KT, Lee YC. Human gastric microbiota transplantation recapitulates premalignant lesions in germ-free mice. Gut 2022; 71:1266-1276. [PMID: 34389621 DOI: 10.1136/gutjnl-2021-324489] [Citation(s) in RCA: 37] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Accepted: 07/28/2021] [Indexed: 12/26/2022]
Abstract
OBJECTIVE Gastric cancer (GC) is a leading cause of cancer-related mortality. Although microbes besides Helicobacter pylori may also contribute to gastric carcinogenesis, wild-type germ-free (GF) mouse models investigating the role of human gastric microbiota in the process are not yet available. We aimed to evaluate the histopathological features of GF mouse stomachs transplanted with gastric microbiota from patients with different gastric disease states and their relationships with the microbiota. DESIGN Microbiota profiles in corpus and antrum tissues and gastric fluid from 12 patients with gastric dysplasia or GC were analysed. Thereafter, biopsied corpus and antrum tissues and gastric fluid from patients (n=15 and n=12, respectively) with chronic superficial gastritis, intestinal metaplasia or GC were inoculated into 42 GF C57BL/6 mice. The gastric microbiota was analysed by amplicon sequencing. Histopathological features of mouse stomachs were analysed immunohistochemically at 1 month after inoculation. An independent set of an additional 15 GF mice was also analysed at 1 year. RESULTS The microbial community structures of patients with dysplasia or GC in the corpus and antrum were similar. The gastric microbiota from patients with intestinal metaplasia or GC selectively colonised the mouse stomachs and induced premalignant lesions: loss of parietal cells and increases in inflammation foci, in F4/80 and Ki-67 expression, and in CD44v9/GSII lectin expression. Marked dysplastic changes were noted at 1 year post inoculation. CONCLUSION Major histopathological features of premalignant changes are reproducible in GF mice transplanted with gastric microbiota from patients with intestinal metaplasia or GC. Our results suggest that GF mice are useful for analysing the causality of associations reported in human gastric microbiome studies.
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Affiliation(s)
- Soon-Kyeong Kwon
- Department of Systems Biology, Division of Life Sciences, and Institute for Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea.,Division of Applied Life Science (Brain Korea 21), Gyeongsang National University, Jinju, Republic of Korea
| | - Jun Chul Park
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Kwang H Kim
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jaekyung Yoon
- Department of Systems Biology, Division of Life Sciences, and Institute for Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Yejin Cho
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Buhyun Lee
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Jin-Jae Lee
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea.,Department of Life Science, Hallym University, Chuncheon, Republic of Korea
| | - Haengdueng Jeong
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yeseul Oh
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Sung-Hee Kim
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - So Dam Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Bo Ram Hwang
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yusook Chung
- Department of Systems Biology, Division of Life Sciences, and Institute for Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea
| | - Jihyun F Kim
- Department of Systems Biology, Division of Life Sciences, and Institute for Life Science and Biotechnology, Yonsei University, Seoul, Republic of Korea .,Strategic Initiative for Microbiomes in Agriculture and Food, Yonsei University, Seoul, Republic of Korea
| | - Ki Taek Nam
- Severance Biomedical Science Institute, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea
| | - Yong Chan Lee
- Department of Internal Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, Republic of Korea
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Mazumder S, Bindu S, De R, Debsharma S, Pramanik S, Bandyopadhyay U. Emerging role of mitochondrial DAMPs, aberrant mitochondrial dynamics and anomalous mitophagy in gut mucosal pathogenesis. Life Sci 2022; 305:120753. [PMID: 35787999 DOI: 10.1016/j.lfs.2022.120753] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/13/2022] [Accepted: 06/27/2022] [Indexed: 12/22/2022]
Abstract
Gastroduodenal inflammation and ulcerative injuries are increasing due to expanding socio-economic stress, unhealthy food habits-lifestyle, smoking, alcoholism and usage of medicines like non-steroidal anti-inflammatory drugs. In fact, gastrointestinal (GI) complications, associated with the prevailing COVID-19 pandemic, further, poses a challenge to global healthcare towards safeguarding the GI tract. Emerging evidences have discretely identified mitochondrial dysfunctions as common etiological denominators in diseases. However, it is worth realizing that mitochondrial dysfunctions are not just consequences of diseases. Rather, damaged mitochondria severely aggravate the pathogenesis thereby qualifying as perpetrable factors worth of prophylactic and therapeutic targeting. Oxidative and nitrosative stress due to endogenous and exogenous stimuli triggers mitochondrial injury causing production of mitochondrial damage associated molecular patterns (mtDAMPs), which, in a feed-forward loop, inflicts inflammatory tissue damage. Mitochondrial structural dynamics and mitophagy are crucial quality control parameters determining the extent of mitopathology and disease outcomes. Interestingly, apart from endogenous factors, mitochondria also crosstalk and in turn get detrimentally affected by gut pathobionts colonized during luminal dysbiosis. Although mitopathology is documented in various pre-clinical/clinical studies, a comprehensive account appreciating the mitochondrial basis of GI mucosal pathologies is largely lacking. Here we critically discuss the molecular events impinging on mitochondria along with the interplay of mitochondria-derived factors in fueling mucosal pathogenesis. We specifically emphasize on the potential role of aberrant mitochondrial dynamics, anomalous mitophagy, mitochondrial lipoxidation and ferroptosis as emerging regulators of GI mucosal pathogenesis. We finally discuss about the prospect of mitochondrial targeting for next-generation drug discovery against GI disorders.
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Affiliation(s)
- Somnath Mazumder
- Department of Zoology, Raja Peary Mohan College, 1 Acharya Dhruba Pal Road, Uttarpara, West Bengal 712258, India
| | - Samik Bindu
- Department of Zoology, Cooch Behar Panchanan Barma University, Cooch Behar, West Bengal 736101, India
| | - Rudranil De
- Amity Institute of Biotechnology, Amity University, Kolkata, Plot No: 36, 37 & 38, Major Arterial Road, Action Area II, Kadampukur Village, Newtown, Kolkata, West Bengal 700135, India
| | - Subhashis Debsharma
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Saikat Pramanik
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India
| | - Uday Bandyopadhyay
- Division of Infectious Diseases and Immunology, CSIR-Indian Institute of Chemical Biology, 4 Raja S.C. Mullick Road, Kolkata, West Bengal 700032, India; Division of Molecular Medicine, Bose Institute, EN 80, Sector V, Bidhan Nagar, Kolkata, West Bengal 700091, India.
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45
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Caldwell B, Meyer AR, Weis JA, Engevik AC, Choi E. Chief cell plasticity is the origin of metaplasia following acute injury in the stomach mucosa. Gut 2022; 71:1068-1077. [PMID: 34497145 PMCID: PMC8901801 DOI: 10.1136/gutjnl-2021-325310] [Citation(s) in RCA: 36] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/03/2021] [Accepted: 08/31/2021] [Indexed: 12/12/2022]
Abstract
OBJECTIVE Metaplasia arises from differentiated cell types in response to injury and is considered a precursor in many cancers. Heterogeneous cell lineages are present in the reparative metaplastic mucosa with response to injury, including foveolar cells, proliferating cells and spasmolytic polypeptide-expressing metaplasia (SPEM) cells, a key metaplastic cell population. Zymogen-secreting chief cells are long-lived cells in the stomach mucosa and have been considered the origin of SPEM cells; however, a conflicting paradigm has proposed isthmal progenitor cells as an origin for SPEM. DESIGN Gastric intrinsic factor (GIF) is a stomach tissue-specific gene and exhibits protein expression unique to mature mouse chief cells. We generated a novel chief cell-specific driver mouse allele, GIF-rtTA. GIF-GFP reporter mice were used to validate specificity of GIF-rtTA driver in chief cells. GIF-Cre-RnTnG mice were used to perform lineage tracing during homoeostasis and acute metaplasia development. L635 treatment was used to induce acute mucosal injury and coimmunofluorescence staining was performed for various gastric lineage markers. RESULTS We demonstrated that mature chief cells, rather than isthmal progenitor cells, serve as the predominant origin of SPEM cells during the metaplastic process after acute mucosal injury. Furthermore, we observed long-term label-retaining chief cells at 1 year after the GFP labelling in chief cells. However, only a very small subset of the long-term label-retaining chief cells displayed the reprogramming ability in homoeostasis. In contrast, we identified chief cell-originating SPEM cells as contributing to lineages within foveolar cell hyperplasia in response to the acute mucosal injury. CONCLUSION Our study provides pivotal evidence for cell plasticity and lineage contributions from differentiated gastric chief cells during acute metaplasia development.
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Affiliation(s)
- Brianna Caldwell
- Section of Surgical Sciences and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Anne R Meyer
- Section of Surgical Sciences and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Jared A Weis
- Department of Biomedical Engineering, Wake Forest School of Medicine, Winston-Salem, North Carolina, USA
| | - Amy C Engevik
- Section of Surgical Sciences and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Eunyoung Choi
- Section of Surgical Sciences and Epithelial Biology Center, Vanderbilt University Medical Center, Nashville, Tennessee, USA
- Department of Cell and Developmental Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, USA
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46
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Dey P, Ray Chaudhuri S. Cancer-Associated Microbiota: From Mechanisms of Disease Causation to Microbiota-Centric Anti-Cancer Approaches. BIOLOGY 2022; 11:757. [PMID: 35625485 PMCID: PMC9138768 DOI: 10.3390/biology11050757] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 04/10/2022] [Revised: 05/08/2022] [Accepted: 05/12/2022] [Indexed: 02/07/2023]
Abstract
Helicobacter pylori infection is the only well-established bacterial cause of cancer. However, due to the integral role of tissue-resident commensals in maintaining tissue-specific immunometabolic homeostasis, accumulated evidence suggests that an imbalance of tissue-resident microbiota that are otherwise considered as commensals, can also promote various types of cancers. Therefore, the present review discusses compelling evidence linking tissue-resident microbiota (especially gut bacteria) with cancer initiation and progression. Experimental evidence supporting the cancer-causing role of gut commensal through the modulation of host-specific processes (e.g., bile acid metabolism, hormonal effects) or by direct DNA damage and toxicity has been discussed. The opportunistic role of commensal through pathoadaptive mutation and overcoming colonization resistance is discussed, and how chronic inflammation triggered by microbiota could be an intermediate in cancer-causing infections has been discussed. Finally, we discuss microbiota-centric strategies, including fecal microbiota transplantation, proven to be beneficial in preventing and treating cancers. Collectively, this review provides a comprehensive understanding of the role of tissue-resident microbiota, their cancer-promoting potentials, and how beneficial bacteria can be used against cancers.
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Affiliation(s)
- Priyankar Dey
- Department of Biotechnology, Thapar Institute of Engineering and Technology, Patiala 147004, India
| | - Saumya Ray Chaudhuri
- Council of Scientific and Industrial Research (CSIR), Institute of Microbial Technology, Chandigarh 160036, India;
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Liatsos C, Papaefthymiou A, Kyriakos N, Galanopoulos M, Doulberis M, Giakoumis M, Petridou E, Mavrogiannis C, Rokkas T, Kountouras J. Helicobacter pylori, gastric microbiota and gastric cancer relationship: Unrolling the tangle. World J Gastrointest Oncol 2022; 14:959-972. [PMID: 35646287 PMCID: PMC9124990 DOI: 10.4251/wjgo.v14.i5.959] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 05/12/2021] [Accepted: 04/09/2022] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori infection (Hp-I) represents a typical microbial agent intervening in the complex mechanisms of gastric homeostasis by disturbing the balance between the host gastric microbiota and mucosa-related factors, leading to inflammatory changes, dysbiosis and eventually gastric cancer. The normal gastric microbiota shows diversity, with Proteobacteria [Helicobacter pylori (H. pylori) belongs to this family], Firmicutes, Actinobacteria, Bacteroides and Fusobacteria being the most abundant phyla. Most studies indicate that H. pylori has inhibitory effects on the colonization of other bacteria, harboring a lower diversity of them in the stomach. When comparing the healthy with the diseased stomach, there is a change in the composition of the gastric microbiome with increasing abundance of H. pylori (where present) in the gastritis stage, while as the gastric carcinogenesis cascade progresses to gastric cancer, the oral and intestinal-type pathogenic microbial strains predominate. Hp-I creates a premalignant environment of atrophy and intestinal metaplasia and the subsequent alteration in gastric microbiota seems to play a crucial role in gastric tumorigenesis itself. Successful H. pylori eradication is suggested to restore gastric microbiota, at least in primary stages. It is more than clear that Hp-I, gastric microbiota and gastric cancer constitute a challenging tangle and the strong interaction between them makes it difficult to unroll. Future studies are considered of crucial importance to test the complex interaction on the modulation of the gastric microbiota by H. pylori as well as on the relationships between the gastric microbiota and gastric carcinogenesis.
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Affiliation(s)
- Christos Liatsos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Apostolis Papaefthymiou
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
- Gastroenterology, University Hospital of Larissa, Larissa 41336, Greece
| | - Nikolaos Kyriakos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michail Galanopoulos
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Michael Doulberis
- Division of Gastroenterology and Hepatology, Medical University Department, Kantonsspital Aarau, Aarau 1234, Switzerland
| | - Marios Giakoumis
- Department of Gastroenterology, 401 General Military Hospital of Athens, Athens 11525, Greece
| | - Evangelia Petridou
- Department of Microbiology, “Agia Sofia” Paediatric Hospital, Goudi, Athens 11527, Greece
| | - Christos Mavrogiannis
- Gastrointestinal and Liver Unit, Faculty of Nursing, Kifissia General and Oncology Hospital, Kaliftaki, N.Kifisia 14564, Greece
| | - Theodore Rokkas
- Gastroenterological Clinic, Henry Dunant Hospital, Athens 11525, Greece
| | - Jannis Kountouras
- Department of Internal Medicine, Second Medical Clinic, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki 41336, Macedonia, Greece
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48
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Zhao L, Liu Y, Zhang S, Wei L, Cheng H, Wang J, Wang J. Impacts and mechanisms of metabolic reprogramming of tumor microenvironment for immunotherapy in gastric cancer. Cell Death Dis 2022; 13:378. [PMID: 35444235 PMCID: PMC9021207 DOI: 10.1038/s41419-022-04821-w] [Citation(s) in RCA: 53] [Impact Index Per Article: 17.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2022] [Accepted: 04/04/2022] [Indexed: 02/07/2023]
Abstract
Metabolic disorders and abnormal immune function changes occur in tumor tissues and cells to varying degrees. There is increasing evidence that reprogrammed energy metabolism contributes to the development of tumor suppressive immune microenvironment and influences the course of gastric cancer (GC). Current studies have found that tumor microenvironment (TME) also has important clinicopathological significance in predicting prognosis and therapeutic efficacy. Novel approaches targeting TME therapy, such as immune checkpoint blockade (ICB), metabolic inhibitors and key enzymes of immune metabolism, have been involved in the treatment of GC. However, the interaction between GC cells metabolism and immune metabolism and how to make better use of these immunotherapy methods in the complex TME in GC are still being explored. Here, we discuss how metabolic reprogramming of GC cells and immune cells involved in GC immune responses modulate anti-tumor immune responses, as well as the effects of gastrointestinal flora in TME and GC. It is also proposed how to enhance anti-tumor immune response by understanding the targeted metabolism of these metabolic reprogramming to provide direction for the treatment and prognosis of GC.
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Affiliation(s)
- Lin Zhao
- The First Clinical College, Changzhi Medical College, Changzhi, Shanxi, 046000, China
| | - Yuanyuan Liu
- The First Clinical College, Changzhi Medical College, Changzhi, Shanxi, 046000, China
| | - Simiao Zhang
- The First Clinical College, Changzhi Medical College, Changzhi, Shanxi, 046000, China
| | - Lingyu Wei
- Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China.,Key Laboratory of Esophageal Cancer Basic Research and Clinical Transformation, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 046000, China
| | - Hongbing Cheng
- Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China.,Department of Microbiology, Changzhi Medical College, Changzhi, Shanxi, 046000, China
| | - Jinsheng Wang
- Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China. .,Key Laboratory of Esophageal Cancer Basic Research and Clinical Transformation, Heping Hospital Affiliated to Changzhi Medical College, Changzhi, Shanxi, 046000, China.
| | - Jia Wang
- Collaborative Innovation Center for Aging Mechanism Research and Transformation, Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China. .,Department of Immunology, Center for Healthy Aging, Changzhi Medical College, Changzhi, Shanxi, 046000, China.
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Yin J, Che G, Wang W, Chen S, Liu J. Investigating the Prognostic Significance of Pyroptosis-Related Genes in Gastric Cancer and Their Impact on Cells' Biological Functions. Front Oncol 2022; 12:861284. [PMID: 35419279 PMCID: PMC8995648 DOI: 10.3389/fonc.2022.861284] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/24/2022] [Accepted: 03/01/2022] [Indexed: 11/16/2022] Open
Abstract
Objective To probe into the role of pyroptosis-related genes in gastric cancer. Methods To establish pyroptosis-related genes, observe their expression in gastric cancer, and analyze the prognosis of pyroptosis-related genes in gastric cancer by single-factor COX, which showed that only GSDME had prognostic significance in gastric cancer. The mRNA expression profiles and lncRNA expression profiles of gastric cancer downloaded from the Cancer Genome Atlas were combined for weighted gene regulatory network analysis, after which the lncRNA nodes of the module to which GSDME belongs were extracted to obtain the lncRNAs−GSDME interactions, which were visualized with Cytoscape network plots. Finally, the effects of GSDME on the proliferation, migration, and apoptosis of gastric cancer cells were observed with CCK8, and flow cytometry. Results Our results show that only GSDME has prognostic significance in gastric cancer, and show that it has an important role in a variety of tumors. In addition, our results show that 16 lncRNAs have a significant interaction with GSDME. Finally, the experimental analysis showed that knocking down the expression level of GSDME could affect the growth as well as apoptosis of gastric cancer cells. Conclusion The significant prognostic significance of GSDME in gastric cancer and the fact that affecting GSDME expression inhibits gastric cancer cell growth suggest that GSDME can be used as a predictive biomarker.
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Affiliation(s)
- Jie Yin
- Department of Radiation Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Che
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Wankun Wang
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shitu Chen
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jian Liu
- Department of Surgical Oncology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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50
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Role of Gastric Microorganisms Other than Helicobacter pylori in the Development and Treatment of Gastric Diseases. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6263423. [PMID: 35321071 PMCID: PMC8938066 DOI: 10.1155/2022/6263423] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 09/17/2021] [Revised: 12/02/2021] [Accepted: 02/18/2022] [Indexed: 12/15/2022]
Abstract
The microenvironment in the stomach is different from other digestive tracts, mainly because of the secretion of gastric acid and digestive enzymes, bile reflux, special mucus barrier, gastric peristalsis, and so on, which all contribute to the formation of antibacterial environment. Microecological disorders can lead to gastric immune disorders or lead to the decrease of dominant bacteria and the increase of the abundance and virulence of pathogenic microorganisms and then promote the occurrence of diseases. The body performs its immune function through innate and adaptive immunity and maintains microbial balance through the mechanism of immune homeostasis. Microecological imbalance can lead to the invasion of pathogenic microorganisms and damage mucosal barrier and immune system. The coexistence of gastric microorganisms (including viruses and fungi) may play a synergistic or antagonistic role in the pathogenesis of gastric diseases. Probiotics have the ability to compete with intestinal pathogens, increase the secretion of immunoglobulin A (IgA), stimulate the production of mucin, bacteriocin, and lactic acid, regulate the expression and secretion of cytokines, and regulate the growth of microbiota, which all have beneficial effects on the host microbial environment. At present, most studies focused on Helicobacter pylori, ignoring other stomach microbes and the overall stomach microecology. So, in this article, we reviewed advances in human gastric microecology, the relationship between gastric microecology and immunity or gastric diseases, and the treatment of probiotics in gastric diseases, in order to explore new area for further study of gastric microorganisms and treatment of gastric diseases.
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