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Clyne M, Ó Cróinín T. Pathogenicity and virulence of Helicobacter pylori: A paradigm of chronic infection. Virulence 2025; 16:2438735. [PMID: 39725863 DOI: 10.1080/21505594.2024.2438735] [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: 05/13/2024] [Revised: 11/18/2024] [Accepted: 12/02/2024] [Indexed: 12/28/2024] Open
Abstract
Infection with Helicobacter pylori is one of the most common infections of mankind. Infection typically occurs in childhood and persists for the lifetime of the host unless eradicated with antimicrobials. The organism colonizes the stomach and causes gastritis. Most infected individuals are asymptomatic, but infection also causes gastric and duodenal ulceration, and gastric cancer. H. pylori possesses an arsenal of virulence factors, including a potent urease enzyme for protection from acid, flagella that mediate motility, an abundance of outer membrane proteins that can mediate attachment, several immunomodulatory proteins, and an ability to adapt to specific conditions in individual human stomachs. The presence of a type 4 secretion system that injects effector molecules into gastric cells and subverts host cell signalling is associated with virulence. In this review we discuss the interplay of H. pylori colonization and virulence factors with host and environmental factors to determine disease outcome in infected individuals.
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Affiliation(s)
- Marguerite Clyne
- School of Medicine, University College Dublin, Dublin, Ireland
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
| | - Tadhg Ó Cróinín
- The Conway Institute of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
- School of Biomolecular and Biomedical Science, University College Dublin, Dublin, Ireland
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Fei X, Li N, Xu X, Zhu Y. Macrophage biology in the pathogenesis of Helicobacter pylori infection. Crit Rev Microbiol 2025; 51:399-416. [PMID: 39086061 DOI: 10.1080/1040841x.2024.2366944] [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: 08/03/2023] [Revised: 05/31/2024] [Accepted: 06/04/2024] [Indexed: 08/02/2024]
Abstract
Infection with H. pylori induces chronic gastric inflammation, progressing to peptic ulcer and stomach adenocarcinoma. Macrophages function as innate immune cells and play a vital role in host immune defense against bacterial infection. However, the distinctive mechanism by which H. pylori evades phagocytosis allows it to colonize the stomach and further aggravate gastric preneoplastic pathology. H. pylori exacerbates gastric inflammation by promoting oxidative stress, resisting macrophage phagocytosis, and inducing M1 macrophage polarization. M2 macrophages facilitate the proliferation, invasion, and migration of gastric cancer cells. Various molecular mechanisms governing macrophage function in the pathogenesis of H. pylori infection have been identified. In this review, we summarize recent findings of macrophage interactions with H. pylori infection, with an emphasis on the regulatory mechanisms that determine the clinical outcome of bacterial infection.
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Affiliation(s)
- Xiao Fei
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Nianshuang Li
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Xinbo Xu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
| | - Yin Zhu
- Department of Gastroenterology, Digestive Disease Hospital, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- Jiangxi Provincial Key Laboratory of Digestive Diseases, Department of Gastroenterology, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, China
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Chen D, Wang W, Chen X, Liang N, Li J, Ding W, Zhang H, Yang Z, Zhao H, Liu Z. Plant-derived extracts or compounds for Helicobacter-associated gastritis: a systematic review of their anti-Helicobacter activity and anti-inflammatory effect in animal experiments. Chin Med 2025; 20:53. [PMID: 40264171 PMCID: PMC12013188 DOI: 10.1186/s13020-025-01093-2] [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: 06/21/2024] [Accepted: 03/10/2025] [Indexed: 04/24/2025] Open
Abstract
BACKGROUND Helicobacter infection, which is the leading cause of gastritis and stomach cancer, has become common worldwide. Almost all Helicobacter-infected patients have chronic active gastritis, also known as Helicobacter-associated gastritis (HAG). However, the eradication rate of Helicobacter is decreasing due to the poor efficacy of current medications, which causes infection to recur, inflammation to persist, and stomach cancer to develop. Natural components have robust antibacterial activity and anti-inflammatory capacity, as confirmed by many studies of alternative natural medicines. PURPOSE This article aimed to conduct a comprehensive search and meta-analysis to evaluate the efficacy of anti-Helicobacter and anti-inflammatory activities of plant-derived extracts or compounds that can treat HAG in animal experiments. We intended to provide detailed preclinical-research foundation including plant and compound information, as well as the mechanisms by which these plant-derived substances inhibit the progression of Helicobacter infection, gastritis and neoplasms for future study. METHODS The systematic review is aligned with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, and the protocol was registered in PROSPERO (CRD42024527889). An extensive search was performed across multiple databases, including PubMed, Scopus, Web of Science, Embase, China National Knowledge Infrastructure (CNKI), the Chinese Scientific Journal database (VIP), the Wanfang database, and the China biomedical literature service system (SinoMed), up until November 2023. Meta-analysis on Review Manager software (RevMan 5.4) estimating anti-Helicobacter and anti-inflammatory activity was performed. We used the Systematic Review Center for Laboratory Animal Experimentation (SYRCLE) risk of bias tool to evaluate the risk of bias of each study included. RESULTS Our study encompassed 61 researches, comprised 36 extracts and 37 compounds improving HAG by inhibiting Helicobacter infection, the inflammatory response, oxidative stress, and regulating apoptosis and proliferation. Sixteen families especially Asteraceae, Fabaceae and Rosaceae and nine classes including Terpenoids, Alkaloids, Phenols, and Flavonoids may be promising directions for valuable new drugs. The Meta-analyse demonstrated the plant-base substance treatments possess significant anti-Helicobacter and anti-inflammation activity comparing to control groups. The included plants and compounds confirmed that signaling pathways NF-κB, JAK2/STAT3, MAPK, TLR4/MyD88, PI3K/AKT, NLRP3/Caspase-1 and NRF2/HO-1 play a key role in the progression of HAG. CONCLUSION Plant-derived extracts or compounds actively improve HAG by modulating relevant mechanisms and signaling pathways, particularly through the anti-Helicobacter and inflammatory regulation ways. Further researches to apply these treatments in humans are needed, which will provide direction for the future development of therapeutic drugs to increase eradication rate and alleviate gastritis.
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Affiliation(s)
- Danni Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wenlai Wang
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China
| | - Xiangyun Chen
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Ning Liang
- Institute of Basic Research in Clinical Medicine, China Academy of Chinese Medical Sciences, Beijing, 100700, China
| | - Jiawang Li
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Wei Ding
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China
| | - Hongrui Zhang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China
| | - Zhen Yang
- College of Traditional Chinese Medicine, Beijing University of Chinese Medicine, No. 11 Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, China.
| | - Hongxia Zhao
- Institute of Basic Theory for Chinese Medicine, China Academy of Chinese Medical Sciences, No. 16 Nanxiaojie, Dongzhimen Nei, Dongcheng District, Beijing, 100700, China.
| | - Zhenhong Liu
- Dongzhimen Hospital, Beijing University of Chinese Medicine, No. 5 Haiyuncang, Dongcheng District, Beijing, 100700, China.
- Institute for Brain Disorders, Beijing University of Chinese Medicine, Beijing, 100700, China.
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Zheng Y, Zhang T, Shao J, Du Y, Li Z, Zhang L, Gao J. Antibiotic-free responsive biomaterials for specific and targeted Helicobacter pylori eradication. J Control Release 2025; 379:708-729. [PMID: 39863021 DOI: 10.1016/j.jconrel.2025.01.054] [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: 08/03/2024] [Revised: 12/17/2024] [Accepted: 01/20/2025] [Indexed: 01/27/2025]
Abstract
Gastric cancer is highly correlated with Helicobacter pylori (H. pylori) infection. Approximately 50 % of the population worldwide is infected with H. pylori. However, current treatment regimens face severe challenges including drug resistance and gut microbiota disruption. An integrative treatment with slight negative influences on intestinal flora, conforming with concepts of integrative prevention of gastric cancer, is urgently needed. Non-antibiotic responsive biomaterials can respond to different stimuli, including pH, enzymes, light, ultrasound and magnetism, under which biomaterials are specifically activated to perform antibacterial capabilities, while neutral intestinal microenvironments differ from gastric microenvironments or inflammatory sites and have no or minimal irradiation via precisely controlled exogenous stimuli, which may not only overcome antibiotic resistance but also avoid gut microbiota disorders. First, the latest progress in responsive biomaterials against H. pylori without gut microbiome disturbance and their anti-H. pylori performances are profoundly summarized. Second, the mechanisms against planktonic bacteria, biofilms and intracellular bacteria are discussed respectively. Finally, the strategies of specific and targeted H. pylori elimination by responsive biomaterials are introduced. Additionally, the challenges and the focus of future research on translation into clinical application are fully proposed. Antibiotic-free responsive biomaterials for specific and targeted H. pylori eradication represent an innovative approach.
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Affiliation(s)
- Yating Zheng
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Yangzhou Branch of Jiangsu Provincial Corps of Chinese People's Armed Police Force, Yangzhou 225007, Jiangsu, China
| | - Tinglin Zhang
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, China
| | - Juan Shao
- Yangzhou Branch of Jiangsu Provincial Corps of Chinese People's Armed Police Force, Yangzhou 225007, Jiangsu, China
| | - Yiqi Du
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, China
| | - Zhaoshen Li
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, China
| | - Li Zhang
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, China.
| | - Jie Gao
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai 200433, China; Shanghai Key Laboratory of Nautical Medicine and Translation of Drugs and Medical Devices, Shanghai, China.
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Turocy T, Crawford JM. Bacterial small molecule metabolites implicated in gastrointestinal cancer development. Nat Rev Microbiol 2025; 23:106-121. [PMID: 39375475 DOI: 10.1038/s41579-024-01103-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/28/2024] [Indexed: 10/09/2024]
Abstract
Numerous associations have been identified between cancer and the composition and function of the human microbiome. As cancer remains the second leading global cause of mortality, investigating the carcinogenic contributions of microbiome members could advance our understanding of cancer risk and support potential therapeutic interventions. Although fluctuations in bacterial species have been associated with cancer progression, studying their small molecule metabolites offers one avenue to establish support for causal relationships and the molecular mechanisms governing host-microorganism interactions. In this Review, we explore the expanding repertoire of small molecule metabolites and their mechanisms implicated in the risk of developing gastrointestinal cancers.
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Affiliation(s)
- Tayah Turocy
- Department of Chemistry, Yale University, New Haven, CT, USA
- Institute of Biomolecular Design and Discovery, Yale University, West Haven, CT, USA
| | - Jason M Crawford
- Department of Chemistry, Yale University, New Haven, CT, USA.
- Institute of Biomolecular Design and Discovery, Yale University, West Haven, CT, USA.
- Department of Microbial Pathogenesis, Yale University School of Medicine, New Haven, CT, USA.
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Duan Y, Xu Y, Dou Y, Xu D. Helicobacter pylori and gastric cancer: mechanisms and new perspectives. J Hematol Oncol 2025; 18:10. [PMID: 39849657 PMCID: PMC11756206 DOI: 10.1186/s13045-024-01654-2] [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: 08/20/2024] [Accepted: 12/23/2024] [Indexed: 01/25/2025] Open
Abstract
Gastric cancer remains a significant global health challenge, with Helicobacter pylori (H. pylori) recognized as a major etiological agent, affecting an estimated 50% of the world's population. There has been a rapidly expanding knowledge of the molecular and pathogenetic mechanisms of H. pylori over the decades. This review summarizes the latest research advances to elucidate the molecular mechanisms underlying the H. pylori infection in gastric carcinogenesis. Our investigation of the molecular mechanisms reveals a complex network involving STAT3, NF-κB, Hippo, and Wnt/β-catenin pathways, which are dysregulated in gastric cancer caused by H. pylori. Furthermore, we highlight the role of H. pylori in inducing oxidative stress, DNA damage, chronic inflammation, and cell apoptosis-key cellular events that pave the way for carcinogenesis. Emerging evidence also suggests the effect of H. pylori on the tumor microenvironment and its possible implications for cancer immunotherapy. This review synthesizes the current knowledge and identifies gaps that warrant further investigation. Despite the progress in our previous knowledge of the development in H. pylori-induced gastric cancer, a comprehensive investigation of H. pylori's role in gastric cancer is crucial for the advancement of prevention and treatment strategies. By elucidating these mechanisms, we aim to provide a more in-depth insights for the study and prevention of H. pylori-related gastric cancer.
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Affiliation(s)
- Yantao Duan
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yonghu Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Yi Dou
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China
| | - Dazhi Xu
- Department of Gastric Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
- Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
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Choi S, Shin M, Kim WY. Targeting the DNA damage response (DDR) of cancer cells with natural compounds derived from Panax ginseng and other plants. J Ginseng Res 2025; 49:1-11. [PMID: 39872282 PMCID: PMC11764321 DOI: 10.1016/j.jgr.2024.04.001] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2024] [Revised: 03/30/2024] [Accepted: 04/01/2024] [Indexed: 01/30/2025] Open
Abstract
DNA damage is a driver of cancer formation, leading to the impairment of repair mechanisms in cancer cells and rendering them susceptible to DNA-damaging therapeutic approaches. The concept of "synthetic lethality" in cancer clinics has emerged, particularly with the use of PARP inhibitors and the identification of DNA damage response (DDR) mutation biomarkers, emphasizing the significance of targeting DDR in cancer therapy. Novel approaches aimed at genome maintenance machinery are under development to further enhance the efficacy of cancer treatments. Natural compounds from traditional medicine, renowned for their anti-aging and anticarcinogenic properties, have garnered attention. Ginseng-derived compounds, in particular, exhibit anti-carcinogenic effects by suppressing reactive oxygen species (ROS) and protecting cells from DNA damage-induced carcinogenesis. However, the anticancer therapeutic effect of ginseng compounds has also been demonstrated by inducing DNA damage and blocking DDR. This review concentrates on the biphasic effects of ginseng compounds on DNA mutations-both inhibiting mutation accumulation and impairing DNA repair. Additionally, it explores other natural compounds targeting DDR directly, providing potential insights into enhancing cancer therapy efficacy.
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Affiliation(s)
- SeokGyeong Choi
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
| | - Minwook Shin
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
| | - Woo-Young Kim
- College of Pharmacy, Sookmyung Women's University, Seoul, Republic of Korea
- Muscle Physiome Research Center, Sookmyung Women's University, Seoul, Republic of Korea
- Research Institute of Pharmaceutical Sciences, Sookmyung Women's University, Seoul, Republic of Korea
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Chen A, Huang H, Fang S, Hang Q. ROS: A "booster" for chronic inflammation and tumor metastasis. Biochim Biophys Acta Rev Cancer 2024; 1879:189175. [PMID: 39218404 DOI: 10.1016/j.bbcan.2024.189175] [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: 05/09/2024] [Revised: 08/22/2024] [Accepted: 08/26/2024] [Indexed: 09/04/2024]
Abstract
Reactive oxygen species (ROS) are a group of highly active molecules produced by normal cellular metabolism and play a crucial role in the human body. In recent years, researchers have increasingly discovered that ROS plays a vital role in the progression of chronic inflammation and tumor metastasis. The inflammatory tumor microenvironment established by chronic inflammation can induce ROS production through inflammatory cells. ROS can then directly damage DNA or indirectly activate cellular signaling pathways to promote tumor metastasis and development, including breast cancer, lung cancer, liver cancer, colorectal cancer, and so on. This review aims to elucidate the relationship between ROS, chronic inflammation, and tumor metastasis, explaining how chronic inflammation can induce tumor metastasis and how ROS can contribute to the evolution of chronic inflammation toward tumor metastasis. Interestingly, ROS can have a "double-edged sword" effect, promoting tumor metastasis in some cases and inhibiting it in others. This article also highlights the potential applications of ROS in inhibiting tumor metastasis and enhancing the precision of tumor-targeted therapy. Combining ROS with nanomaterials strategies may be a promising approach to enhance the efficacy of tumor treatment.
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Affiliation(s)
- Anqi Chen
- Medical College, Yangzhou University, Yangzhou 225009, China
| | - Haifeng Huang
- Department of Laboratory Medicine, The First People's Hospital of Yancheng, Yancheng 224006, China; Department of Laboratory Medicine, Yancheng Clinical Medical College of Jiangsu University, Yancheng 224006, China
| | - Sumeng Fang
- School of Mathematics, Tianjin University, Tianjin 300350, China
| | - Qinglei Hang
- Jiangsu Provincial Innovation and Practice Base for Postdoctors, Suining People's Hospital, Affiliated Hospital of Xuzhou Medical University, Suining 221200, China; Key Laboratory of Jiangsu Province University for Nucleic Acid & Cell Fate Manipulation, Yangzhou University, Yangzhou 225009, China; Department of Laboratory Medicine, Medical College, Yangzhou University, Yangzhou 225009, China.
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Kolahi Sadeghi L, Vahidian F, Eterafi M, Safarzadeh E. Gastrointestinal cancer resistance to treatment: the role of microbiota. Infect Agent Cancer 2024; 19:50. [PMID: 39369252 PMCID: PMC11453072 DOI: 10.1186/s13027-024-00605-3] [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: 06/15/2024] [Accepted: 08/20/2024] [Indexed: 10/07/2024] Open
Abstract
The most common illnesses that adversely influence human health globally are gastrointestinal malignancies. The prevalence of gastrointestinal cancers (GICs) is relatively high, and the majority of patients receive ineffective care since they are discovered at an advanced stage of the disease. A major component of the human body is thought to be the microbiota of the gastrointestinal tract and the genes that make up the microbiome. The gut microbiota includes more than 3000 diverse species and billions of microbes. Each of them has benefits and drawbacks and been demonstrated to alter anticancer medication efficacy. Treatment of GIC with the help of the gut bacteria is effective while changes in the gut microbiome which is linked to resistance immunotherapy or chemotherapy. Despite significant studies and findings in this field, more research on the interactions between microbiota and response to treatment in GIC are needed to help researchers provide more effective therapeutic strategies with fewer treatment complication. In this review, we examine the effect of the human microbiota on anti-cancer management, including chemotherapy, immunotherapy, and radiotherapy.
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Affiliation(s)
- Leila Kolahi Sadeghi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Fatemeh Vahidian
- Faculty of Medicine, Laval University, Quebec, Canada
- Centre de Recherche de I'Institut Universitaire de Cardiologie et de Pneumologie de Québec (IUCPQ), Quebec, Canada
| | - Majid Eterafi
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran
- Students' Research Committee, Ardabil University of Medical Sciences, Ardabil, Iran
| | - Elham Safarzadeh
- Cancer Immunology and Immunotherapy Research Center, Ardabil University of Medical Sciences, Ardabil, Iran.
- Department of Microbiology, Parasitology, and Immunology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran.
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Moe KT, Tan KSW. Mechanistic Insights on Microbiota-Mediated Development and Progression of Esophageal Cancer. Cancers (Basel) 2024; 16:3305. [PMID: 39409925 PMCID: PMC11475040 DOI: 10.3390/cancers16193305] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2024] [Revised: 09/18/2024] [Accepted: 09/24/2024] [Indexed: 10/20/2024] Open
Abstract
Esophageal cancer (EC) is one of the most common malignant tumors worldwide, and its two major types, esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC), present a severe global public health problem with an increasing incidence and mortality. Established risk factors include smoking, alcohol consumption, and dietary habits, but recent research has highlighted the substantial role of oral microbiota in EC pathogenesis. This review explores the intricate relationship between the microbiome and esophageal carcinogenesis, focusing on the following eight significant mechanisms: chronic inflammation, microbial dysbiosis, production of carcinogenic metabolites, direct interaction with epithelial cells, epigenetic modifications, interaction with gastroesophageal reflux disease (GERD), metabolic changes, and angiogenesis. Certain harmful bacteria, such as Porphyromonas gingivalis and Fusobacterium nucleatum, are specifically implicated in sustaining irritation and tumor progression through pathways including NF-κB and NLRP3 inflammasome. Additionally, the review explores how microbial byproducts, including short-chain fatty acids (SCFAs) and reactive oxygen species (ROS), contribute to DNA harm and disease advancement. Furthermore, the impact of reflux on microbiota composition and its role in esophageal carcinogenesis is evaluated. By combining epidemiological data with mechanistic understanding, this review underscores the potential to target the microbiota-immune system interplay for novel therapeutic and diagnostic strategies to prevent and treat esophageal cancer.
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Affiliation(s)
- Kyaw Thu Moe
- Biomedical Sciences, Newcastle University Medicine Malaysia, Iskandar Puteri 79200, Johor, Malaysia
| | - Kevin Shyong-Wei Tan
- Laboratory of Molecular and Cellular Parasitology, Health Longevity Translational Research Programme, Department of Microbiology and Immunology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive, Singapore 117545, Singapore
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Shao G, Liu Y, Lu L, Wang L, Ji G, Xu H. Therapeutic potential of traditional Chinese medicine in the prevention and treatment of digestive inflammatory cancer transformation: Portulaca oleracea L. as a promising drug. JOURNAL OF ETHNOPHARMACOLOGY 2024; 327:117999. [PMID: 38447616 DOI: 10.1016/j.jep.2024.117999] [Citation(s) in RCA: 13] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/10/2024] [Revised: 02/19/2024] [Accepted: 02/28/2024] [Indexed: 03/08/2024]
Abstract
ETHNOPHARMACOLOGICAL RELEVANCE Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. AIM OF STUDY In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. METHODS The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. RESULTS Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. CONCLUSION The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.
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Affiliation(s)
- Gaoxuan Shao
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Ying Liu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Lu Lu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China
| | - Lei Wang
- Department of Hepatology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China
| | - Guang Ji
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China.
| | - Hanchen Xu
- Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, China; Shanghai Frontiers Science Center of Disease and Syndrome Biology of Inflammatory Cancer Transformation, China.
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12
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Shu C, Zhang W, Zhang Y, Li Y, Xu X, Zhou Y, Zhang Y, Zhong Q, He C, Zhu Y, Wang X. Copper-Bearing Metal-Organic Framework with Mucus-Penetrating Function for the Multi-Effective Clearance of Mucosal Colonized Helicobacter pylori. RESEARCH (WASHINGTON, D.C.) 2024; 7:0358. [PMID: 38779487 PMCID: PMC11109517 DOI: 10.34133/research.0358] [Citation(s) in RCA: 6] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 01/23/2024] [Accepted: 03/28/2024] [Indexed: 05/25/2024]
Abstract
Helicobacter pylori colonizes over 50% of people worldwide. Biofilm formation through penetrating gastric mucus and resistance acquired by H. pylori markedly reduces the efficacy of traditional antibiotics. The present triple therapy and bismuth-based quadruple therapy inevitably causes intestinal flora disturbance and fails to address the excessive H. pylori-triggered inflammatory response. Herein, a mucus-permeable therapeutic platform (Cu-MOF@NF) that consists of copper-bearing metal-organic framework (Cu-MOF) loaded with nitrogen-doped carbon dots and naturally active polysaccharide fucoidan is developed. The experimental results demonstrate that Cu-MOF@NF can penetrate the mucus layer and hinder H. pylori from adhering on gastric epithelial cells of the stomach. Notably, released Cu2+ can degrade the polysaccharides in the biofilm and interfere with the cyclic growing mode of "bacterioplankton ↔ biofilm", thereby preventing recurrent and persistent infection. Compared with traditional triple therapy, the Cu-MOF@NF not only possesses impressive antibacterial effect (even include multidrug-resistant strains), but also improves the inflammatory microenvironment without disrupting the balance of intestinal flora, providing a more efficient, safe, and antibiotic-free new approach to eradicating H. pylori.
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Affiliation(s)
- Chunxi Shu
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
| | - Wei Zhang
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
- Postdoctoral Innovation Practice Base, The First Affiliated Hospital, Jiangxi Medical College,
Nanchang University, Nanchang 330006, China
| | - Yiwei Zhang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine,
Nanchang University, Nanchang 330088, China
| | - Yu Li
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine,
Nanchang University, Nanchang 330088, China
| | - Xinbo Xu
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
| | - Yanan Zhou
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
| | - Yue Zhang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine,
Nanchang University, Nanchang 330088, China
| | - Qin Zhong
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine,
Nanchang University, Nanchang 330088, China
| | - Cong He
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
| | - Yin Zhu
- Department of Gastroenterology, The First Affiliated Hospital,
Jiangxi Medical College Nanchang University, Nanchang 330006, China
| | - Xiaolei Wang
- The National Engineering Research Center for Bioengineering Drugs and the Technologies, Institute of Translational Medicine,
Nanchang University, Nanchang 330088, China
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13
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Zhang C, Chen Y, Long Y, Zheng H, Jing J, Pan W. Helicobacter pylori and Gastrointestinal Cancers: Recent Advances and Controversies. Clin Med Insights Oncol 2024; 18:11795549241234637. [PMID: 38558880 PMCID: PMC10979532 DOI: 10.1177/11795549241234637] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2023] [Accepted: 02/01/2024] [Indexed: 04/04/2024] Open
Abstract
Helicobacter pylori (H pylori), a gastric bacterium, has been extensively studied for its association with gastritis, peptic ulcers, and gastric cancer. However, recent evidence suggests its potential implications beyond the stomach, linking it to other gastrointestinal malignancies, such as esophageal cancer, liver cancer, pancreatic cancer, gallbladder cancer, and colorectal cancer. In light of the expanding research landscape and the increasing interest in exploring H pylori broader role in gastrointestinal tumorigenesis, this comprehensive review aims to elucidate the relationship between H pylori and gastrointestinal tumors. This review encompasses recent epidemiological studies, research progress, and emerging perspectives, providing a comprehensive assessment of the relationship between H pylori and gastrointestinal tumors. The findings highlight the captivating world of H pylori and its intricate involvement in gastrointestinal malignancies.
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Affiliation(s)
- Chuandong Zhang
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Clinical Medicine, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Yuqi Chen
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Clinical Medicine, Qingdao Medical College, Qingdao University, Qingdao, China
| | - Yan Long
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Huimin Zheng
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Department of Clinical Medicine, Bengbu Medical College, Bengbu, China
| | - Jiyong Jing
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
| | - Wensheng Pan
- Cancer Center, Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, China
- Zhejiang Provincial Engineering Laboratory of Diagnosis, Treatment and Pharmaceutical Development of Gastrointestinal Tract Tumors, Hangzhou, China
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14
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Shi L, Shangguan J, Lu Y, Rong J, Yang Q, Yang Y, Xie C, Shu X. ROS-mediated up-regulation of SAE1 by Helicobacter pylori promotes human gastric tumor genesis and progression. J Transl Med 2024; 22:148. [PMID: 38351014 PMCID: PMC10863176 DOI: 10.1186/s12967-024-04913-5] [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: 08/28/2023] [Accepted: 01/19/2024] [Indexed: 02/16/2024] Open
Abstract
Helicobacter pylori (H. pylori) is a major risk factor of gastric cancer (GC). The SUMO-activating enzyme SAE1(SUMO-activating enzyme subunit 1), which is indispensable for protein SUMOylation, involves in human tumorigenesis. In this study, we used the TIMER and TCGA database to explore the SAE1 expression in GC and normal tissues and Kaplan-Meier Plotter platform for survival analysis of GC patients. GC tissue microarray and gastric samples from patients who underwent endoscopic treatment were employed to detect the SAE1expression. Our results showed that SAE1 was overexpressed in GC tissues and higher SAE1 expression was associated with worse clinical characteristics of GC patients. Cell and animal models showed that H. pylori infection upregulated SAE1, SUMO1, and SUMO2/3 protein expression. Functional assays suggested that suppression of SAE1 attenuated epithelial-mesenchymal transition (EMT) biomarkers and cell proliferation abilities induced by H. pylori. Cell and animal models of ROS inhibition in H. pylori showed that ROS could mediate the H. pylori-induced upregulation of SAE1, SUMO1, and SUMO2/3 protein. RNA sequencing was performed and suggested that knockdown of SAE1 could exert an impact on IGF-1 expression. General, increased SUMOylation modification is involved in H. pylori-induced GC.
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Affiliation(s)
- Liu Shi
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
- Department of Gastroenterology, The Affiliated Ganzhou Hospital of Nanchang University, No.16, Meiguan Avenue, Ganzhou, 341000, Jiangxi, China
| | - Jianfang Shangguan
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Ying Lu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Jianfang Rong
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Qinyu Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Yihan Yang
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China
| | - Chuan Xie
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
| | - Xu Shu
- Department of Gastroenterology, The First Affiliated Hospital of Nanchang University, NO. 17 Yongwaizheng Street, Nanchang, 330006, Jiangxi, China.
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15
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Soutto M, Zhang X, Bhat N, Chen Z, Zhu S, Maacha S, Genoula M, El-Gazzaz O, Peng D, Lu H, McDonald OG, Chen XS, Cao L, Xu Z, El-Rifai W. Fibroblast growth factor receptor-4 mediates activation of Nuclear Factor Erythroid 2-Related Factor-2 in gastric tumorigenesis. Redox Biol 2024; 69:102998. [PMID: 38154380 PMCID: PMC10787301 DOI: 10.1016/j.redox.2023.102998] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/13/2023] [Indexed: 12/30/2023] Open
Abstract
Helicobacter pylori (H. pylori) is the leading risk factor for gastric carcinogenesis. Fibroblast growth factor receptor 4 (FGFR4) is a member of transmembrane tyrosine kinase receptors that are activated in cancer. We investigated the role of FGFR4 in regulating the cellular response to H. pylori infection in gastric cancer. High levels of oxidative stress signature and FGFR4 expression were detected in gastric cancer samples. Gene set enrichment analysis (GSEA) demonstrated enrichment of NRF2 signature in samples with high FGFR4 levels. H. pylori infection induced reactive oxygen species (ROS) with a cellular response manifested by an increase in FGFR4 with accumulation and nuclear localization NRF2. Knocking down FGFR4 significantly reduced NRF2 protein and transcription activity levels, leading to higher levels of ROS and DNA damage following H. pylori infection. We confirmed the induction of FGFR4 and NRF2 levels using mouse models following infection with a mouse-adapted H. pyloristrain. Pharmacologic inhibition of FGFR4 using H3B-6527, or its knockdown, remarkably reduced the level of NRF2 with a reduction in the size and number of gastric cancer spheroids. Mechanistically, we detected binding between FGFR4 and P62 proteins, competing with NRF2-KEAP1 interaction, allowing NRF2 to escape KEAP1-dependent degradation with subsequent accumulation and translocation to the nucleus. These findings demonstrate a novel functional role of FGFR4 in cellular homeostasis via regulating the NRF2 levels in response to H. pylori infection in gastric carcinogenesis, calling for testing the therapeutic efficacy of FGFR4 inhibitors in gastric cancer models.
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Affiliation(s)
- Mohammed Soutto
- Department of Veterans Affairs, Miami Healthcare System, Miami, FL, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Xing Zhang
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210009, China
| | - Nadeem Bhat
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Zheng Chen
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Shoumin Zhu
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Selma Maacha
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Melanie Genoula
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Omar El-Gazzaz
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Dunfa Peng
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Heng Lu
- Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Oliver G McDonald
- Department of Pathology, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Xi Steven Chen
- Division of Biostatistics, Department of Public Health Science, Sylvester Comprehensive Cancer Center, University of Miami Miller School of Medicine, Miami, FL, 33136, USA
| | - Longlong Cao
- Department of Gastric Surgery, Fujian Medical University Union Hospital, Fuzhou, China
| | - Zekuan Xu
- Department of General Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210029, China; Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Jiangsu Collaborative Innovation Center for Cancer Personalized Medicine, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, 211166, China
| | - Wael El-Rifai
- Department of Veterans Affairs, Miami Healthcare System, Miami, FL, USA; Department of Surgery, University of Miami Miller School of Medicine, Miami, FL, 33136, USA.
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16
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Engin AB, Engin A. Tryptophan Metabolism in Obesity: The Indoleamine 2,3-Dioxygenase-1 Activity and Therapeutic Options. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2024; 1460:629-655. [PMID: 39287867 DOI: 10.1007/978-3-031-63657-8_21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 09/19/2024]
Abstract
Obesity activates both innate and adaptive immune responses in adipose tissue. Adipose tissue macrophages are functional antigen-presenting cells that promote the proliferation of interferon-gamma (IFN-γ)-producing cluster of differentiation (CD)4+ T cells in adipose tissue of obese subjects. The increased formation of neopterin and degradation of tryptophan may result in decreased T-cell responsiveness and lead to immunodeficiency. The activity of inducible indoleamine 2,3-dioxygenase-1 (IDO1) plays a major role in pro-inflammatory, IFN-γ-dominated settings. The expression of several kynurenine pathway enzyme genes is significantly increased in obesity. IDO1 in obesity shifts tryptophan metabolism from serotonin and melatonin synthesis to the formation of kynurenines and increases the ratio of kynurenine to tryptophan as well as with neopterin production. Reduction in serotonin (5-hydroxytryptamine; 5-HT) production provokes satiety dysregulation that leads to increased caloric uptake and obesity. According to the monoamine-deficiency hypothesis, a deficiency of cerebral serotonin is involved in neuropsychiatric symptomatology of depression, mania, and psychosis. Indeed, bipolar disorder (BD) and related cognitive deficits are accompanied by a higher prevalence of overweight and obesity. Furthermore, the accumulation of amyloid-β in Alzheimer's disease brains has several toxic effects as well as IDO induction. Hence, abdominal obesity is associated with vascular endothelial dysfunction. kynurenines and their ratios are prognostic parameters in coronary artery disease. Increased kynurenine/tryptophan ratio correlates with increased intima-media thickness and represents advanced atherosclerosis. However, after bariatric surgery, weight reduction does not lead to the normalization of IDO1 activity and atherosclerosis. IDO1 is involved in the mechanisms of immune tolerance and in the concept of tumor immuno-editing process in cancer development. Serum IDO1 activity is still used as a parameter in cancer development and growth. IDO-producing tumors show a high total IDO immunostaining score, and thus, using IDO inhibitors, such as Epacadostat, Navoximod, and L isomer of 1-methyl-tryptophan, seems an important modality for cancer treatment. There is an inverse correlation between serum folate concentration and body mass index, thus folate deficiency leads to hyperhomocysteinemia-induced oxidative stress. Immune checkpoint blockade targeting cytotoxic T-lymphocyte-associated protein-4 synergizes with imatinib, which is an inhibitor of mitochondrial folate-mediated one-carbon (1C) metabolism. Antitumor effects of imatinib are enhanced by increasing T-cell effector function in the presence of IDO inhibition. Combining IDO targeting with chemotherapy, radiotherapy and/or immunotherapy, may be an effective tool against a wide range of malignancies. However, there are some controversial results regarding the efficacy of IDO1 inhibitors in cancer treatment.
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Affiliation(s)
- Ayse Basak Engin
- Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey.
| | - Atilla Engin
- Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey
- Mustafa Kemal Mah. 2137. Sok. 8/14, 06520, Cankaya, Ankara, Turkey
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17
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Wu S, Chen Y, Chen Z, Wei F, Zhou Q, Li P, Gu Q. Reactive oxygen species and gastric carcinogenesis: The complex interaction between Helicobacter pylori and host. Helicobacter 2023; 28:e13024. [PMID: 37798959 DOI: 10.1111/hel.13024] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 09/10/2023] [Accepted: 09/21/2023] [Indexed: 10/07/2023]
Abstract
Helicobacter pylori (H. pylori) is a highly successful human pathogen that colonizes stomach in around 50% of the global population. The colonization of bacterium induces an inflammatory response and a substantial rise in the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS), mostly derived from host neutrophils and gastric epithelial cells, which play a crucial role in combating bacterial infections. However, H. pylori has developed various strategies to quench the deleterious effects of ROS, including the production of antioxidant enzymes, antioxidant proteins as well as blocking the generation of oxidants. The host's inability to eliminate H. pylori infection results in persistent ROS production. Notably, excessive ROS can disrupt the intracellular signal transduction and biological processes of the host, incurring chronic inflammation and cellular damage, such as DNA damage, lipid peroxidation, and protein oxidation. Markedly, the sustained inflammatory response and oxidative stress during H. pylori infection are major risk factor for gastric carcinogenesis. In this context, we summarize the literature on H. pylori infection-induced ROS production, the strategies used by H. pylori to counteract the host response, and subsequent host damage and gastric carcinogenesis.
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Affiliation(s)
- Shiying Wu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Yongqiang Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Ziqi Chen
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Fangtong Wei
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Qingqing Zhou
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Ping Li
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
| | - Qing Gu
- Key Laboratory for Food Microbial Technology of Zhejiang Province, College of Food Science and Biotechnology, Zhejiang Gongshang University, Hangzhou, China
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18
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Chattopadhyay I, Gundamaraju R, Rajeev A. Diversification and deleterious role of microbiome in gastric cancer. Cancer Rep (Hoboken) 2023; 6:e1878. [PMID: 37530125 PMCID: PMC10644335 DOI: 10.1002/cnr2.1878] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/07/2023] [Revised: 06/20/2023] [Accepted: 07/22/2023] [Indexed: 08/03/2023] Open
Abstract
Gut microbiota dictates the fate of several diseases, including cancer. Most gastric cancers (GC) belong to gastric adenocarcinomas (GAC). Helicobacter pylori colonizes the gastric epithelium and is the causative agent of 75% of all stomach malignancies globally. This bacterium has several virulence factors, including cytotoxin-associated gene A (CagA), vacuolating cytotoxin (VacA), and outer membrane proteins (OMPs), all of which have been linked to the development of gastric cancer. In addition, bacteria such as Escherichia coli, Streptococcus, Clostridium, Haemophilus, Veillonella, Staphylococcus, and Lactobacillus play an important role in the development of gastric cancer. Besides, lactic acid bacteria (LAB) such as Bifidobacterium, Lactobacillus, Lactococcus, and Streptococcus were found in greater abundance in GAC patients. To identify potential diagnostic and therapeutic interventions for GC, it is essential to understand the mechanistic role of H. pylori and other bacteria that contribute to gastric carcinogenesis. Furthermore, understanding bacteria-host interactions and bacteria-induced inflammatory pathways in the host is critical for developing treatment targets for gastric cancer.
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Affiliation(s)
| | - Rohit Gundamaraju
- ER stress and Mucosal Immunology TeamSchool of Health Sciences, University of TasmaniaLauncestonTasmaniaAustralia
| | - Ashwin Rajeev
- Department of BiotechnologyCentral University of Tamil NaduThiruvarurIndia
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19
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Reyes A, Ortiz G, Duarte LF, Fernández C, Hernández-Armengol R, Palacios PA, Prado Y, Andrade CA, Rodriguez-Guilarte L, Kalergis AM, Simon F, Carreño LJ, Riedel CA, Cáceres M, González PA. Contribution of viral and bacterial infections to senescence and immunosenescence. Front Cell Infect Microbiol 2023; 13:1229098. [PMID: 37753486 PMCID: PMC10518457 DOI: 10.3389/fcimb.2023.1229098] [Citation(s) in RCA: 14] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2023] [Accepted: 08/24/2023] [Indexed: 09/28/2023] Open
Abstract
Cellular senescence is a key biological process characterized by irreversible cell cycle arrest. The accumulation of senescent cells creates a pro-inflammatory environment that can negatively affect tissue functions and may promote the development of aging-related diseases. Typical biomarkers related to senescence include senescence-associated β-galactosidase activity, histone H2A.X phosphorylation at serine139 (γH2A.X), and senescence-associated heterochromatin foci (SAHF) with heterochromatin protein 1γ (HP-1γ protein) Moreover, immune cells undergoing senescence, which is known as immunosenescence, can affect innate and adaptative immune functions and may elicit detrimental effects over the host's susceptibility to infectious diseases. Although associations between senescence and pathogens have been reported, clear links between both, and the related molecular mechanisms involved remain to be determined. Furthermore, it remains to be determined whether infections effectively induce senescence, the impact of senescence and immunosenescence over infections, or if both events coincidently share common molecular markers, such as γH2A.X and p53. Here, we review and discuss the most recent reports that describe cellular hallmarks and biomarkers related to senescence in immune and non-immune cells in the context of infections, seeking to better understand their relationships. Related literature was searched in Pubmed and Google Scholar databases with search terms related to the sections and subsections of this review.
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Affiliation(s)
- Antonia Reyes
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Gerardo Ortiz
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Luisa F. Duarte
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
- Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Christian Fernández
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago, Chile
| | - Rosario Hernández-Armengol
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Pablo A. Palacios
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Yolanda Prado
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Catalina A. Andrade
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Linmar Rodriguez-Guilarte
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Alexis M. Kalergis
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
- Departamento de Endocrinología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile
| | - Felipe Simon
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Leandro J. Carreño
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Programa de Inmunología, Instituto de Ciencias Biomédicas, Facultad de Medicina, Universidad de Chile, Santiago, Chile
| | - Claudia A. Riedel
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias de la Vida, Universidad Andres Bello, Santiago, Chile
| | - Mónica Cáceres
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Program of Cellular and Molecular Biology, Institute of Biomedical Sciences, Faculty of Medicine, Universidad de Chile, Millennium Nucleus of Ion Channel-Associated Diseases (MiNICAD), Santiago, Chile
| | - Pablo A. González
- Millennium Institute on Immunology and Immunotherapy, Santiago, Chile
- Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile
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20
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Li B, Lv X, Xu Z, He J, Liu S, Zhang X, Tong X, Li J, Zhang Y. Helicobacter pylori infection induces autophagy via ILK regulation of NOXs-ROS-Nrf2/HO-1-ROS loop. World J Microbiol Biotechnol 2023; 39:284. [PMID: 37599292 DOI: 10.1007/s11274-023-03710-4] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/04/2022] [Accepted: 07/21/2023] [Indexed: 08/22/2023]
Abstract
Reactive oxygen species (ROS) can regulate the occurrence of autophagy, and effective control of the balance between ROS and autophagy may be an important strategy for Helicobacter pylori induced gastric-related diseases. In this study, infection with H. pylori led to a lower level of ILK phosphorylation and increased ROS generation. Knockdown of ILK enhanced total ROS generation, and upregulated NADPH oxidase (NOX) subunit p22-phox levels. Inhibition of NOXs affected total ROS generation. The inhibition of NOX and ROS generation reduced Nrf2 and HO-1 levels, and knockdown of ILK significantly enhanced Nrf2 levels in H. pylori-infected GES-1 cells. Activation of Nrf2 by DMF decreased ROS levels. Therefore, NOX-dependent ROS production regulated by ILK was essential for activation of Nrf2/HO-1 signaling pathways in H. pylori-infected GES-1 cells. Beclin1, ATG5 and LC3B-II levels were higher both in H. pylori-infected and ILK-knockdown GES-1 cells. In NAC-pretreated GES-1 cells infected with H. pylori, the LC3B-II level was decreased compared to that in cells after H. pylori infection alone. Stable low expression of ILK with further knockdown of Beclin1 or ATG5 significantly reduced LC3B-II levels in GES-1 cells, while with the addition of the autophagy inhibitor chloroquine (CQ), LC3B-II and p62 protein levels were both remarkably upregulated. H. pylori accelerated the accumulation of ROS and further led to the induction of ROS-mediated autophagy by inhibiting ILK levels. Together, these results indicate that H. pylori infection manipulates the NOX-ROS-Nrf2/HO-1-ROS loop to control intracellular oxygen stress and further induced ROS-mediated autophagy by inhibiting ILK levels.
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Affiliation(s)
- Boqing Li
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Xin Lv
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Zheng Xu
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Jing He
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - SiSi Liu
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Xiaolin Zhang
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Xiaohan Tong
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Jing Li
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China
| | - Ying Zhang
- School of Basic Medical Sciences, Binzhou Medical University, 346# Guanhai Road, Yantai, 264003, China.
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21
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Zarezadeh M, Mahmoudinezhad M, Hosseini B, Khorraminezhad L, Razaghi M, Alvandi E, Saedisomeolia A. Dietary pattern in autism increases the need for probiotic supplementation: A comprehensive narrative and systematic review on oxidative stress hypothesis. Clin Nutr 2023; 42:1330-1358. [PMID: 37418842 DOI: 10.1016/j.clnu.2023.06.014] [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: 02/28/2023] [Revised: 05/15/2023] [Accepted: 06/11/2023] [Indexed: 07/09/2023]
Abstract
Autism spectrum disorders (ASDs) are associated with specific dietary habits, including limited food selection and gastrointestinal problems, resulting in an altered gut microbiota. Autistic patients have an elevated abundance of certain gut bacteria associated with increased oxidative stress in the gastrointestinal tract. Probiotic supplementation has been shown to decrease oxidative stress in a simulated gut model, but the antioxidant effects of probiotics on the oxidative stress of the gut in autistic patients have not been directly studied. However, it is speculated that probiotic supplementation may help decrease oxidative stress in the gastrointestinal tract of autistic patients due to their specific dietary habits altering the microbiota. PubMed, Scopus and Web of Science databases and Google Scholar were searched up to May 2023. This systematic-narrative review aims to present the latest evidence regarding the changes in eating habits of autistic children which may further increase the gut microbiota induced oxidative stress. Additionally, this review will assess the available literature on the effects of probiotic supplementation on oxidative stress parameters.
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Affiliation(s)
- Meysam Zarezadeh
- Student Research Committee, Tabriz University of Medical Sciences, Tabriz, Iran
| | | | - Banafshe Hosseini
- Clinical Research and Knowledge Transfer Unit on Childhood Asthma, Research Centre, Sainte-Justine University Health Centre, Montreal, QC H3T 1C5, Canada
| | - Leila Khorraminezhad
- School of Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada
| | - Maryam Razaghi
- Department of Nutritional Sciences, Faculty of Medicine, University of Toronto, Toronto, ON, Canada
| | - Ehsan Alvandi
- School of Medicine, Western Sydney University, NSW, Australia
| | - Ahmad Saedisomeolia
- School of Human Nutrition, McGill University, Ste-Anne-de-Bellevue, Québec, Canada.
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22
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Yin X, Lai Y, Du Y, Zhang T, Gao J, Li Z. Metal-Based Nanoparticles: A Prospective Strategy for Helicobacter pylori Treatment. Int J Nanomedicine 2023; 18:2413-2429. [PMID: 37192898 PMCID: PMC10182771 DOI: 10.2147/ijn.s405052] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2023] [Accepted: 03/24/2023] [Indexed: 05/18/2023] Open
Abstract
Helicobacter pylori (H. pylori) is an infectious pathogen and the leading cause of gastrointestinal diseases, including gastric adenocarcinoma. Currently, bismuth quadruple therapy is the recommended first-line treatment, and it is reported to be highly effective, with >90% eradication rates on a consistent basis. However, the overuse of antibiotics causes H. pylori to become increasingly resistant to antibiotics, making its eradication unlikely in the foreseeable future. Besides, the effect of antibiotic treatments on the gut microbiota also needs to be considered. Therefore, effective, selective, antibiotic-free antibacterial strategies are urgently required. Due to their unique physiochemical properties, such as the release of metal ions, the generation of reactive oxygen species, and photothermal/photodynamic effects, metal-based nanoparticles have attracted a great deal of interest. In this article, we review recent advances in the design, antimicrobial mechanisms and applications of metal-based nanoparticles for the eradication of H. pylori. Additionally, we discuss current challenges in this field and future perspectives that may be used in anti-H. pylori strategies.
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Affiliation(s)
- Xiaojing Yin
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Yongkang Lai
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
- Department of Gastroenterology, Ganzhou People’s Hospital Affiliated to Nanchang University, Ganzhou, Jiangxi, 341000, People’s Republic of China
| | - Yiqi Du
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Tinglin Zhang
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Jie Gao
- Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
| | - Zhaoshen Li
- Department of Gastroenterology, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China
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23
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Duizer C, de Zoete MR. The Role of Microbiota-Derived Metabolites in Colorectal Cancer. Int J Mol Sci 2023; 24:8024. [PMID: 37175726 PMCID: PMC10178193 DOI: 10.3390/ijms24098024] [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: 03/19/2023] [Revised: 04/25/2023] [Accepted: 04/25/2023] [Indexed: 05/15/2023] Open
Abstract
The impact of bacterial members of the microbiota on the development of colorectal cancer (CRC) has become clear in recent years. However, exactly how bacteria contribute to the development of cancer is often still up for debate. The impact of bacteria-derived metabolites, which can influence the development of CRC either in a promoting or inhibiting manner, is undeniable. Here, we discuss the effects of the most well-studied bacteria-derived metabolites associated with CRC, including secondary bile acids, short-chain fatty acids, trimethylamine-N-oxide and indoles. We show that the effects of individual metabolites on CRC development are often nuanced and dose- and location-dependent. In the coming years, the array of metabolites involved in CRC development will undoubtedly increase further, which will emphasize the need to focus on causation and mechanisms and the clearly defined roles of bacterial species within the microbiota.
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Affiliation(s)
| | - Marcel R. de Zoete
- Department of Medical Microbiology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
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24
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Kouidhi S, Zidi O, Belkhiria Z, Rais H, Ayadi A, Ben Ayed F, Mosbah A, Cherif A, El Gaaied ABA. Gut microbiota, an emergent target to shape the efficiency of cancer therapy. EXPLORATION OF TARGETED ANTI-TUMOR THERAPY 2023; 4:240-265. [PMID: 37205307 PMCID: PMC10185446 DOI: 10.37349/etat.2023.00132] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/04/2022] [Accepted: 01/04/2023] [Indexed: 05/21/2023] Open
Abstract
It is now well-acknowledged that microbiota has a profound influence on both human health and illness. The gut microbiota has recently come to light as a crucial element that influences cancer through a variety of mechanisms. The connections between the microbiome and cancer therapy are further highlighted by a number of preclinical and clinical evidence, suggesting that these complicated interactions may vary by cancer type, treatment, or even by tumor stage. The paradoxical relationship between gut microbiota and cancer therapies is that in some cancers, the gut microbiota may be necessary to maintain therapeutic efficacy, whereas, in other cancers, gut microbiota depletion significantly increases efficacy. Actually, mounting research has shown that the gut microbiota plays a crucial role in regulating the host immune response and boosting the efficacy of anticancer medications like chemotherapy and immunotherapy. Therefore, gut microbiota modulation, which aims to restore gut microbial balance, is a viable technique for cancer prevention and therapy given the expanding understanding of how the gut microbiome regulates treatment response and contributes to carcinogenesis. This review will provide an outline of the gut microbiota's role in health and disease, along with a summary of the most recent research on how it may influence the effectiveness of various anticancer medicines and affect the growth of cancer. This study will next cover the newly developed microbiota-targeting strategies including prebiotics, probiotics, and fecal microbiota transplantation (FMT) to enhance anticancer therapy effectiveness, given its significance.
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Affiliation(s)
- Soumaya Kouidhi
- Laboratory BVBGR-LR11ES31, Biotechnopole Sidi Thabet, University Manouba, ISBST, Ariana 2020, Tunisia
- Association Tunisienne de Lutte contre le Cancer (ATCC), Tunis, Tunisia
| | - Oumaima Zidi
- Laboratory BVBGR-LR11ES31, Biotechnopole Sidi Thabet, University Manouba, ISBST, Ariana 2020, Tunisia
- Department of Biologu, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 1068, Tunisia
| | | | - Henda Rais
- Association Tunisienne de Lutte contre le Cancer (ATCC), Tunis, Tunisia
- Service d’Oncologie Médicale, Hôpital Salah-Azaïz, Tunis 1006, Tunisia
| | - Aida Ayadi
- Department of Pathology, Abderrahman Mami Hospital, University of Tunis El Manar, Ariana 2080, Tunisia
| | - Farhat Ben Ayed
- Association Tunisienne de Lutte contre le Cancer (ATCC), Tunis, Tunisia
| | - Amor Mosbah
- Laboratory BVBGR-LR11ES31, Biotechnopole Sidi Thabet, University Manouba, ISBST, Ariana 2020, Tunisia
| | - Ameur Cherif
- Laboratory BVBGR-LR11ES31, Biotechnopole Sidi Thabet, University Manouba, ISBST, Ariana 2020, Tunisia
| | - Amel Ben Ammar El Gaaied
- Laboratory of Genetics, Immunology and Human Pathology, Department of Biology, Faculty of Sciences of Tunis, University of Tunis El Manar, Tunis 1068, Tunisia
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25
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Jarmakiewicz-Czaja S, Ferenc K, Filip R. Antioxidants as Protection against Reactive Oxidative Stress in Inflammatory Bowel Disease. Metabolites 2023; 13:metabo13040573. [PMID: 37110231 PMCID: PMC10146410 DOI: 10.3390/metabo13040573] [Citation(s) in RCA: 28] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/27/2023] [Revised: 04/13/2023] [Accepted: 04/16/2023] [Indexed: 04/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) belongs to a group of chronic diseases characterised by periods of exacerbation and remission. Despite many studies and observations, its aetiopathogenesis is still not fully understood. The interactions of genetic, immunological, microbiological, and environmental factors can induce disease development and progression, but there is still a lack of information on these mechanisms. One of the components that can increase the risk of occurrence of IBD, as well as disease progression, is oxidative stress. Oxidative stress occurs when there is an imbalance between reactive oxygen species (ROS) and antioxidants. The endogenous and exogenous components that make up the body's antioxidant defence can significantly affect IBD prophylaxis and reduce the risk of exacerbation by neutralising and removing ROS, as well as influencing the inflammatory state.
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Affiliation(s)
| | - Katarzyna Ferenc
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
| | - Rafał Filip
- Institute of Medicine, Medical College of Rzeszow University, 35-959 Rzeszow, Poland
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland
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26
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Zhao T, Wang H, Liu Z, Liu Y, Li B, Huang X. Recent Perspective of Lactobacillus in Reducing Oxidative Stress to Prevent Disease. Antioxidants (Basel) 2023; 12:antiox12030769. [PMID: 36979017 PMCID: PMC10044891 DOI: 10.3390/antiox12030769] [Citation(s) in RCA: 24] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/16/2023] [Revised: 03/19/2023] [Accepted: 03/20/2023] [Indexed: 03/30/2023] Open
Abstract
During oxidative stress, an important factor in the development of many diseases, cellular oxidative and antioxidant activities are imbalanced due to various internal and external factors such as inflammation or diet. The administration of probiotic Lactobacillus strains has been shown to confer a range of antibacterial, anti-inflammatory, antioxidant, and immunomodulatory effects in the host. This review focuses on the potential role of oxidative stress in inflammatory bowel diseases (IBD), cancer, and liver-related diseases in the context of preventive and therapeutic effects associated with Lactobacillus. This article reviews studies in cell lines and animal models as well as some clinical population reports that suggest that Lactobacillus could alleviate basic symptoms and related abnormal indicators of IBD, cancers, and liver damage, and covers evidence supporting a role for the Nrf2, NF-κB, and MAPK signaling pathways in the effects of Lactobacillus in alleviating inflammation, oxidative stress, aberrant cell proliferation, and apoptosis. This review also discusses the unmet needs and future directions in probiotic Lactobacillus research including more extensive mechanistic analyses and more clinical trials for Lactobacillus-based treatments.
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Affiliation(s)
- Tingting Zhao
- School of Public Health, Lanzhou University, Lanzhou 730033, China
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850000, China
| | - Haoran Wang
- School of Public Health, Lanzhou University, Lanzhou 730033, China
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850000, China
| | - Zhenjiang Liu
- National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun 130012, China
| | - Yang Liu
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850000, China
| | - Bin Li
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850000, China
| | - Xiaodan Huang
- School of Public Health, Lanzhou University, Lanzhou 730033, China
- Institute of Animal Husbandry and Veterinary, Tibet Academy of Agricultural and Animal Husbandry Sciences, Lhasa 850000, China
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27
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Pandey H, Tang DWT, Wong SH, Lal D. Gut Microbiota in Colorectal Cancer: Biological Role and Therapeutic Opportunities. Cancers (Basel) 2023; 15:cancers15030866. [PMID: 36765824 PMCID: PMC9913759 DOI: 10.3390/cancers15030866] [Citation(s) in RCA: 58] [Impact Index Per Article: 29.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/23/2023] [Accepted: 01/24/2023] [Indexed: 02/03/2023] Open
Abstract
Colorectal cancer (CRC) is the second-leading cause of cancer-related deaths worldwide. While CRC is thought to be an interplay between genetic and environmental factors, several lines of evidence suggest the involvement of gut microbiota in promoting inflammation and tumor progression. Gut microbiota refer to the ~40 trillion microorganisms that inhabit the human gut. Advances in next-generation sequencing technologies and metagenomics have provided new insights into the gut microbial ecology and have helped in linking gut microbiota to CRC. Many studies carried out in humans and animal models have emphasized the role of certain gut bacteria, such as Fusobacterium nucleatum, enterotoxigenic Bacteroides fragilis, and colibactin-producing Escherichia coli, in the onset and progression of CRC. Metagenomic studies have opened up new avenues for the application of gut microbiota in the diagnosis, prevention, and treatment of CRC. This review article summarizes the role of gut microbiota in CRC development and its use as a biomarker to predict the disease and its potential therapeutic applications.
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Affiliation(s)
- Himani Pandey
- Redcliffe Labs, Electronic City, Noida 201301, India
| | - Daryl W. T. Tang
- School of Biological Sciences, Nanyang Technological University, Singapore 308232, Singapore
| | - Sunny H. Wong
- Centre for Microbiome Medicine, Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore 308232, Singapore
- Correspondence: (S.H.W.); (D.L.)
| | - Devi Lal
- Department of Zoology, Ramjas College, University of Delhi, Delhi 110007, India
- Correspondence: (S.H.W.); (D.L.)
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28
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Liu Y, Shi Y, Han R, Liu C, Qin X, Li P, Gu R. Signaling pathways of oxidative stress response: the potential therapeutic targets in gastric cancer. Front Immunol 2023; 14:1139589. [PMID: 37143652 PMCID: PMC10151477 DOI: 10.3389/fimmu.2023.1139589] [Citation(s) in RCA: 26] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Accepted: 03/20/2023] [Indexed: 05/06/2023] Open
Abstract
Gastric cancer is one of the top causes of cancer-related death globally. Although novel treatment strategies have been developed, attempts to eradicate gastric cancer have been proven insufficient. Oxidative stress is continually produced and continually present in the human body. Increasing evidences show that oxidative stress contributes significantly to the development of gastric cancer, either through initiation, promotion, and progression of cancer cells or causing cell death. As a result, the purpose of this article is to review the role of oxidative stress response and the subsequent signaling pathways as well as potential oxidative stress-related therapeutic targets in gastric cancer. Understanding the pathophysiology of gastric cancer and developing new therapies for gastric cancer depends on more researches focusing on the potential contributors to oxidative stress and gastric carcinogenesis.
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Affiliation(s)
- Yingying Liu
- School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- Institute for Immunology and School of Medicine, Tsinghua University, Beijing, China
| | - Yu Shi
- Shanghai East Hospital, Tongji University School of Medicine, Shanghai, China
| | - Ruiqin Han
- State Key Laboratory of Medical Molecular Biology, Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Chaoge Liu
- Department of Oromaxillofacial - Head and Neck Surgery, Tianjin Stomatological Hospital, School of Medicine, Nankai University, Tianjin, China
- Tianjin Key Laboratory of Oral and Maxillofacial Function Reconstruction, Tianjin, China
| | - Xiaogang Qin
- Traditional Chinese Medicine Hospital of Tongzhou District, Nantong, Jiangsu, China
- *Correspondence: Renjun Gu, ; Pengfei Li, ; Xiaogang Qin,
| | - Pengfei Li
- Department of Clinical Laboratory, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
- *Correspondence: Renjun Gu, ; Pengfei Li, ; Xiaogang Qin,
| | - Renjun Gu
- School of Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, China
- *Correspondence: Renjun Gu, ; Pengfei Li, ; Xiaogang Qin,
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29
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Kang JH, Park S, Rho J, Hong EJ, Cho YE, Won YS, Kwon HJ. IL-17A promotes Helicobacter pylori-induced gastric carcinogenesis via interactions with IL-17RC. Gastric Cancer 2023; 26:82-94. [PMID: 36125689 PMCID: PMC9813207 DOI: 10.1007/s10120-022-01342-5] [Citation(s) in RCA: 18] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/27/2022] [Accepted: 09/11/2022] [Indexed: 02/07/2023]
Abstract
BACKGROUND Gastric cancer (GC) is a common malignancy worldwide, with a major attribution to Helicobacter pylori. Interleukin (IL)-17A has been reported to be up-regulated in serum and tumor of GC patients, but the precise mechanisms underlying its involvement in gastric tumorigenesis are yet to be established. Here, we investigated the roles of IL-17A in the pathogenesis of H. pylori-induced GC. METHODS GC was induced in IL-17A knockout (KO) and wild-type (WT) mice via N-methyl-N-nitrosourea (MNU) treatment and H. pylori infection. At 50 weeks after treatment, gastric tissues were examined by histopathology, immunohistochemistry, and immunoblot analyses. In vitro experiments on the human GC cell lines were additionally performed to elucidate the underlying mechanisms. RESULTS Deletion of IL-17A suppressed MNU and H. pylori-induced gastric tumor development accompanied by a decrease in gastric epithelial cell growth, oxidative stress, and expression of gastric epithelial stem cells markers. In AGS cells, recombinant human IL-17A (rhIL-17A) inhibited apoptosis and G1/S phase transition arrest while promoting reactive oxygen species production, sphere formation ability of cancer stem cells (CSC), and expression of stemness-related genes. In addition, rhIL-17A induced expression of IL-17RC, leading to NF-κB activation and increased NADPH oxidase 1 (NOX1) levels. Inhibition of NOX1 with GKT136901 attenuated rhIL-17A-mediated elevation of GC cell growth, ROS generation, and CSC stemness. Clinically, IL-17RC expressions were significantly upregulated in human GC compared with normal gastric tissues. CONCLUSION Our results suggest that IL-17A promotes gastric carcinogenesis, in part, by regulating IL-17RC/NF-κB/NOX1 pathway, supporting its potential as a target in human GC therapy.
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Affiliation(s)
- Jee Hyun Kang
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Suyoung Park
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Jinhyung Rho
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Eun-Ju Hong
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea
| | - Young-Eun Cho
- Department of Food and Nutrition, Andong National University, Andong, Korea
| | - Young-Suk Won
- Laboratory Animal Resource Center, Korea Research Institute of Bioscience and Biotechnology, Chungbuk, Korea
| | - Hyo-Jung Kwon
- Department of Veterinary Pathology, College of Veterinary Medicine, Chungnam National University, 99 Daehak-ro, Yuseong-gu, Daejeon, 34134, Korea.
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30
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Chi M, Jiang T, He X, Peng H, Li Y, Zhang J, Wang L, Nian Q, Ma K, Liu C. Role of Gut Microbiota and Oxidative Stress in the Progression of Transplant-Related Complications following Hematopoietic Stem Cell Transplantation. OXIDATIVE MEDICINE AND CELLULAR LONGEVITY 2023; 2023:3532756. [PMID: 37113743 PMCID: PMC10129428 DOI: 10.1155/2023/3532756] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 08/17/2022] [Revised: 10/12/2022] [Accepted: 11/24/2022] [Indexed: 04/29/2023]
Abstract
Hematopoietic stem cell transplantation (HSCT), also known as bone marrow transplantation, has curative potential for various hematologic malignancies but is associated with risks such as graft-versus-host disease (GvHD), severe bloodstream infection, viral pneumonia, idiopathic pneumonia syndrome (IPS), lung fibrosis, and sinusoidal obstruction syndrome (SOS), which severely deteriorate clinical outcomes and limit the wide application of HSCT. Recent research has provided important insights into the effects of gut microbiota and oxidative stress (OS) on HSCT complications. Therefore, based on recent studies, we describe intestinal dysbiosis and OS in patients with HSCT and review recent molecular findings underlying the causal relationships of gut microbiota, OS, and transplant-related complications, focusing particularly on the involvement of gut microbiota-mediated OS in postengraftment complications. Also, we discuss the use of antioxidative and anti-inflammatory probiotics to manipulate gut microbiota and OS, which have been associated with promising effects in improving HSCT outcomes.
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Affiliation(s)
- Mingxuan Chi
- Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
| | - Tao Jiang
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
- Department of Hematology, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan Province 610072, China
| | - Xing He
- School of Clinical Medicine, Chengdu Medical College, China
| | - Haoyu Peng
- School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Yunlong Li
- Department of Urology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
| | - Jiong Zhang
- Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
| | - Li Wang
- Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
| | - Qing Nian
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
- Department of Blood Transfusion, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, China
| | - Kuai Ma
- Department of Nephrology, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Chi Liu
- Department of Nephrology, Sichuan Provincial People's Hospital, Sichuan Renal Disease Clinical Research Center, University of Electronic Science and Technology of China, Chengdu, China
- Chinese Academy of Sciences Sichuan Translational Medicine Research Hospital, Chengdu 610072, China
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Shichiri M, Suzuki H, Isegawa Y, Tamai H. Application of regulation of reactive oxygen species and lipid peroxidation to disease treatment. J Clin Biochem Nutr 2023; 72:13-22. [PMID: 36777080 PMCID: PMC9899923 DOI: 10.3164/jcbn.22-61] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/30/2022] [Accepted: 07/02/2022] [Indexed: 11/05/2022] Open
Abstract
Although many diseases in which reactive oxygen species (ROS) and free radicals are involved in their pathogenesis are known, and antioxidants that effectively capture ROS have been identified and developed, there are only a few diseases for which antioxidants have been used for treatment. Here, we discuss on the following four concepts regarding the development of applications for disease treatment by regulating ROS, free radicals, and lipid oxidation with the findings of our research and previous reports. Concept 1) Utilization of antioxidants for disease treatment. In particular, the importance of the timing of starting antioxidant will be discussed. Concept 2) Therapeutic strategies using ROS and free radicals. Methods of inducing ferroptosis, which has been advocated as an iron-dependent cell death, are mentioned. Concept 3) Treatment with drugs that inhibit the synthesis of lipid mediators. In addition to the reduction of inflammatory lipid mediators by inhibiting cyclooxygenase and leukotriene synthesis, we will introduce the possibility of disease treatment with lipoxygenase inhibitors. Concept 4) Disease treatment by inducing the production of useful lipid mediators for disease control. We describe the treatment of inflammatory diseases utilizing pro-resolving mediators and propose potential compounds that activate lipoxygenase to produce these beneficial mediators.
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Affiliation(s)
- Mototada Shichiri
- Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), 1-8-31 Midorigaoka, Ikeda, Osaka 563-8577, Japan
| | - Hiroshi Suzuki
- National Research Center for Protozoan Diseases, Obihiro University of Agriculture and Veterinary Medicine, Nishi 2-13, Inada-cho, Obihiro, Hokkaido 080-8555, Japan
| | - Yuji Isegawa
- Department of Food Sciences and Nutrition, Mukogawa Women’s University, 6-46 Ikebiraki, Nishinomiya, Hyogo 663-8558, Japan
| | - Hiroshi Tamai
- Department of Pediatrics, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki, Osaka 569-8686, Japan
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32
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Palikova YA, Palikov VA, Novikova NI, Slashcheva GA, Rasskazova EA, Tukhovskaya EA, Danilkovich AV, Dyachenko IA, Belogurov Jr. AA, Kudriaeva AA, Bugrimov DY, Krasnorutskaya ON, Murashev AN. Derinat ® has an immunomodulatory and anti-inflammatory effect on the model of acute lung injury in male SD rats. Front Pharmacol 2022; 13:1111340. [PMID: 36642990 PMCID: PMC9837527 DOI: 10.3389/fphar.2022.1111340] [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: 11/29/2022] [Accepted: 12/16/2022] [Indexed: 12/31/2022] Open
Abstract
To simulate acute lung injury (ALI) in SD male rats they we administered intratracheally with lipopolysaccharide (LPS) followed by hyperventilation of the lungs (HVL), which lead to functional changes in the respiratory system and an increase in the blood serum concentration of inflammatory cytokines. LPS + HVL after 4 h lead to pronounced histological signs of lung damage. We have studied the effectiveness of Derinat® when administered intramuscularly at dose of 7.5 mg/kg for 8 days in the ALI model. Derinat® administration lead to an increase in the concentration of most of the studied cytokines in a day. In the ALI model the administration of Derinat® returned the concentration of cytokines to its original values already 48 h after LPS + HVL, and also normalized the parameters of pulmonary respiration in comparison with animals without treatment. By the eighth day after LPS + HVL, respiratory parameters and cytokine levels, as well as biochemical and hematological parameters did not differ between groups, while histological signs of residual effects of lung damage were found in all animals, and were more pronounced in Derinat® group, which may indicate stimulation of the local immune response. Thus, the administration of Derinat® stimulates the immune response, has a pronounced protective effect against cytokinemia and respiratory failure caused by ALI, has immunomodulatory effect, and also stimulates a local immune response in lung tissues. Thus, Derinat® is a promising treatment for ALI.
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Affiliation(s)
- Yulia A. Palikova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Victor A. Palikov
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Nadezhda I. Novikova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Gulsara A. Slashcheva
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Ekaterina A. Rasskazova
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Elena A. Tukhovskaya
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia,*Correspondence: Elena A. Tukhovskaya,
| | - Alexey V. Danilkovich
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Igor A. Dyachenko
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia
| | - Alexey A. Belogurov Jr.
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (IBCh RAS), 16/10 Miklukho-Maklay Str, Moscow, Russia,Department of Biological Chemistry, Evdokimov Moscow State University of Medicine and Dentistry, Moscow, Russia
| | - Anna A. Kudriaeva
- Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (IBCh RAS), 16/10 Miklukho-Maklay Str, Moscow, Russia
| | - Daniil Y Bugrimov
- Voronezh State Medical University Named After N. N. Burdenko, 10 Studencheskaya Str, Voronezh, Russia
| | - Olga N. Krasnorutskaya
- Voronezh State Medical University Named After N. N. Burdenko, 10 Studencheskaya Str, Voronezh, Russia
| | - Arkady N. Murashev
- Branch of Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences (BIBCh RAS), 6 Prospekt Nauki, Pushchino, Russia,*Correspondence: Elena A. Tukhovskaya,
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Lee J, Kim MH, Kim H. Anti-Oxidant and Anti-Inflammatory Effects of Astaxanthin on Gastrointestinal Diseases. Int J Mol Sci 2022; 23:ijms232415471. [PMID: 36555112 PMCID: PMC9779521 DOI: 10.3390/ijms232415471] [Citation(s) in RCA: 24] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/24/2022] [Revised: 12/02/2022] [Accepted: 12/05/2022] [Indexed: 12/12/2022] Open
Abstract
A moderate amount of reactive oxygen species (ROS) is produced under normal conditions, where they play an important role in cell signaling and are involved in many aspects of the immune response to pathogens. On the other hand, the excessive production of ROS destructs macromolecules, cell membranes, and DNA, and activates pro-inflammatory signaling pathways, which may lead to various pathologic conditions. Gastrointestinal (GI) mucosa is constantly exposed to ROS due to the presence of bacteria and other infectious pathogens in food, as well as alcohol consumption, smoking, and the use of non-steroidal anti-inflammatory drugs (NSAID). Prolonged excessive oxidative stress and inflammation are two major risk factors for GI disorders such as ulcers and cancers. Bioactive food compounds with potent anti-oxidant and anti-inflammatory activity have been tested in experimental GI disease models to evaluate their therapeutic potential. Astaxanthin (AST) is a fat-soluble xanthophyll carotenoid that is naturally present in algae, yeast, salmon, shrimp, and krill. It has been shown that AST exhibits protective effects against GI diseases via multiple mechanisms. Residing at the surface and inside of cell membranes, AST directly neutralizes ROS and lipid peroxyl radicals, enhances the activity of anti-oxidant enzymes, and suppresses pro-inflammatory transcription factors and cytokines. In addition, AST has been shown to inhibit cancer cell growth and metastasis via modulating cell proliferation-related pathways, apoptosis, and autophagy. Considering the potential benefits of AST in GI diseases, this review paper aims to summarize recent advances in AST research, focusing on its anti-oxidant and anti-inflammatory effects against gastric and intestinal ulcers and cancers.
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Affiliation(s)
- Jaeeun Lee
- Department of Food and Nutrition, BK21 FOUR, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
| | - Min-Hyun Kim
- College of Health Solutions, Arizona State University, Phoenix, AZ 85004, USA
- Correspondence: (M.-H.K.); (H.K.); Tel.: +1-602-496-4163 (M.-H.K.); +82-2-2123-3125 (H.K.)
| | - Hyeyoung Kim
- Department of Food and Nutrition, BK21 FOUR, College of Human Ecology, Yonsei University, Seoul 03722, Republic of Korea
- Correspondence: (M.-H.K.); (H.K.); Tel.: +1-602-496-4163 (M.-H.K.); +82-2-2123-3125 (H.K.)
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Zhao Y, Li Z, Zhao L, Wang J, Wang F, Zhang Q, Wang X, Sang Y, Zhan J, He J, Li N, Kang X, Chen J, Wang R. Two novel lactic acid bacteria, Limosilactobacillus fermentum MN-LF23 and Lactobacillus gasseri MN-LG80, inhibited Helicobacter pylori infection in C57BL/6 mice. Food Funct 2022; 13:11061-11069. [PMID: 36197065 DOI: 10.1039/d2fo02034c] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/22/2024]
Abstract
Helicobacter pylori (H. pylori) is one of the most prevalent pathogens globally, and long-term infection causes various gastrointestinal diseases such as gastritis and even cancer. In the present study, we screened dozens of lactic acid bacteria for the efficacy to inhibit H. pylori growth in vitro, and tested the therapeutic effects of candidate strains in vivo. The results showed that Limosilactobacillus fermentum MN-LF23 (LF23) and Lactobacillus gasseri MN-LG80 (LG80) significantly reduced the abundance of Helicobacter by 90% and 83% in the infected mice, respectively, and decreased the levels of serum urease and H. pylori-specific IgG. Both bacterial strains tended to ameliorate H. pylori infection-induced gastric mucosa damage and lymphocyte infiltration, and reduced levels of serum inflammatory cytokines such as TNF-α, IL-1β, and IL-6. In addition, their culture supernatants also showed a therapeutic effect, as efficient as the bacterial cells. Furthermore, both strains significantly regulated gastric microbiota profile, and their supernatants restored the diversity of gastric microbiota. LF23 increased the abundance of Lactobacillus murinus and reduced the abundance of Desulfovibrio, whereas LG80 increased the abundance of Lactobacillus reuteri and reduced the abundance of Bilophila. Both LF23 and LG80 enriched beneficial commensals such as Faecalibaculum rodentium, and reduced detrimental bacteria such as H. pylori and Lachnoclostridium. In conclusion, we identified two novel lactic acid bacteria L. fermentum MN-LF23 and L. gasseri MN-LG80 that can remarkably inhibit H. pylori infection.
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Affiliation(s)
- Yuyang Zhao
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China
| | - Zhipeng Li
- R&D Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd., Huhhot, 011500, Inner Mongolia, China.
- Shanghai Mengniu Biotechnology R&D Co., Ltd., 201210, Shanghai, China
| | - Liang Zhao
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China
| | - Jian Wang
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China
| | - Fan Wang
- R&D Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd., Huhhot, 011500, Inner Mongolia, China.
- Shanghai Mengniu Biotechnology R&D Co., Ltd., 201210, Shanghai, China
| | - Qi Zhang
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China
| | - Xiaoyu Wang
- College of Food Science and Nutritional Engineering, Key Laboratory of Functional Dairy, Co-constructed by Ministry of Education and Beijing Government, China Agricultural University, Beijing 100083, China
| | - Yue Sang
- Hebei Engineering Research Center of Animal Product, Sanhe 065200, China
| | - Jing Zhan
- Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
| | - Jingjing He
- Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
| | - Ning Li
- R&D Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd., Huhhot, 011500, Inner Mongolia, China.
| | - Xiaohong Kang
- R&D Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd., Huhhot, 011500, Inner Mongolia, China.
- Shanghai Mengniu Biotechnology R&D Co., Ltd., 201210, Shanghai, China
| | - Jianguo Chen
- R&D Center, Inner Mongolia Mengniu Dairy (Group) Co. Ltd., Huhhot, 011500, Inner Mongolia, China.
- Shanghai Mengniu Biotechnology R&D Co., Ltd., 201210, Shanghai, China
| | - Ran Wang
- Department of Nutrition and Health, China Agricultural University, Beijing 100190, China.
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Zhang Y, Wang M, Zhang K, Zhang J, Yuan X, Zou G, Cao Z, Zhang C. 6'-O-Galloylpaeoniflorin attenuates Helicobacter pylori-associated gastritis via modulating Nrf2 pathway. Int Immunopharmacol 2022; 111:109122. [PMID: 35964411 DOI: 10.1016/j.intimp.2022.109122] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Revised: 07/27/2022] [Accepted: 07/31/2022] [Indexed: 12/14/2022]
Abstract
As a common disease of the digestive system, chronic gastritis is inflammation of the gastric mucosa caused by various factors. Helicobacter pylori (H. pylori) is one of the main causes of chronic gastritis, which can lead to gastric mucosal damage and gland atrophy, thereby promoting gastrocarcinogenesis. Oxidative stress and the inflammatory response are important mechanisms of H. pylori-induced gastritis. 6'-O-Galloylpaeoniflorin (GPF) is a substance isolated from peony root with antioxidant and anti-inflammatory activities. However, its role and mechanism in the pathogenesis of H. pylori-induced chronic gastritis remain unclear. This study explored the effects of GPF on H. pylori-induced gastric mucosal oxidative stress and inflammation using flow cytometry, western blotting, real-time quantitative PCR, and immunohistochemistry. We found that H. pylori infection increased oxidative stress and expression of inflammatory cytokines in vitro and in vivo and that these outcomes were inhibited by GPF. Furthermore, GPF activated nuclear factor erythroid-related factor-2 (Nrf2) and its downstream target genes in H. pylori-infected GES-1 cells and mice. The anti-inflammatory and antioxidant effects of GPF on H. pylori-infected cells were attenuated by an Nrf2 inhibitor. Taken together, these data suggest that GPF reduces H. pylori-induced gastric mucosa injury by activating Nrf2 signaling and that GPF is a potential candidate for the treatment of H. pylori-associated gastritis.
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Affiliation(s)
- Yun Zhang
- Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 510006, China; Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
| | - Maihuan Wang
- Department of General Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China
| | - Kebin Zhang
- Clinical Medical Research Center, Xinqiao Hospital, Army Medical University, Chongqing 400037, China
| | - Junze Zhang
- The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China
| | - Xinpu Yuan
- Department of General Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China
| | - Guijun Zou
- Department of General Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China
| | - Zhen Cao
- Department of General Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China.
| | - Chaojun Zhang
- Department of General Surgery, School of Medicine, South China University of Technology, Guangzhou 510006, China; Department of General Surgery, The First Medical Center of Chinese, PLA General Hospital, Beijing 100853, China; The Second School of Clinical Medicine, Southern Medical University, Guangzhou 510515, China; Department of General Surgery, The Sixth Medical Center of Chinese PLA General Hospital, Beijing 100048, China.
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36
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Astaxanthin Inhibits Matrix Metalloproteinase Expression by Suppressing PI3K/AKT/mTOR Activation in Helicobacter pylori-Infected Gastric Epithelial Cells. Nutrients 2022; 14:nu14163427. [PMID: 36014933 PMCID: PMC9412703 DOI: 10.3390/nu14163427] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/16/2022] [Accepted: 08/18/2022] [Indexed: 12/13/2022] Open
Abstract
Helicobacter pylori (H. pylori) increases production of reactive oxygen species (ROS) and activates signaling pathways associated with gastric cell invasion, which are mediated by matrix metalloproteinases (MMPs). We previously demonstrated that H. pylori activated mitogen-activated protein kinase (MAPK) and increased expression of MMP-10 in gastric epithelial cells. MMPs degrade the extracellular matrix, enhancing tumor invasion and cancer progression. The signaling pathway of phosphatidylinositol 3-kinase (PI3K)/serine/threonine protein kinase B (AKT)/mammalian target of rapamycin (mTOR) is associated with MMP expression. ROS activates PIK3/AKT/mTOR signaling in cancer. Astaxanthin, a xanthophyll carotenoid, shows antioxidant activity by reducing ROS levels in gastric epithelial cells infected with H. pylori. This study aimed to determine whether astaxanthin inhibits MMP expression, cell invasion, and migration by reducing the PI3K/AKT/mTOR signaling in H. pylori-infected gastric epithelial AGS cells. H. pylori induced PIK3/AKT/mTOR and NF-κB activation, decreased IκBα, and induced MMP (MMP-7 and -10) expression, the invasive phenotype, and migration in AGS cells. Astaxanthin suppressed these H. pylori-induced alterations in AGS cells. Specific inhibitors of PI3K, AKT, and mTOR reversed the H. pylori-stimulated NF-κB activation and decreased IκBα levels in the cells. In conclusion, astaxanthin suppressed MMP expression, cell invasion, and migration via inhibition of PI3K/AKT/mTOR/NF-κB signaling in H. pylori-stimulated gastric epithelial AGS cells.
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α-Lipoic Acid Inhibits Apoptosis by Suppressing the Loss of Ku Proteins in Helicobacter pylori-Infected Human Gastric Epithelial Cells. Nutrients 2022; 14:nu14153206. [PMID: 35956382 PMCID: PMC9370604 DOI: 10.3390/nu14153206] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2022] [Revised: 08/02/2022] [Accepted: 08/03/2022] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a Gram-negative bacterium that colonizes the gastric mucosa and triggers various stomach diseases. H. pylori induces reactive oxygen species (ROS) production and DNA damage. The heterodimeric Ku70/Ku80 protein plays an essential role in the repair of DNA double-strand breaks (DSB). Oxidative stress stimulate apoptosis and DNA damage that can be repaired by Ku70/80. However, excessive reactive oxygen species (ROS) can cause Ku protein degradation, resulting in DNA fragmentation and apoptosis. α-lipoic acid (α-LA), which is found in organ meats such as liver and heart, spinach, broccoli, and potatoes, quenches free radicals, chelates metal ions, and reduces intracellular DNA damage induced by oxidative stress. Here, we investigated whether H. pylori decreases Ku70/80 and induces apoptosis, and whether α-LA inhibits changes induced by H. pylori. We analyzed ROS, DNA damage markers (γ-H2AX, DNA fragmentation), levels of Ku70/80, Ku-DNA binding activity, Ku80 ubiquitination, apoptosis indices (Bcl-2, Bax, apoptosis-inducing factor (AIF), and caspase-3), and viability in a human gastric epithelial adenocarcinoma cell line (AGS). H. pylori increased ROS, DNA damage markers, Ku80 ubiquitination, and consequently induced apoptosis. It also decreased nuclear Ku70/80 levels and Ku-DNA-binding activity; increased Bax expression, caspase-3 cleavage, and truncated AIF; but decreased Bcl-2 expression. These H. pylori-induced alterations were inhibited by α-LA. The antioxidant N-acetylcysteine and proteasome inhibitor MG-132 suppressed H. pylori-induced cell death and decreased nuclear Ku70/80 levels. The results show that oxidative stress induced Ku70/80 degradation via the ubiquitin-proteasome system, leading to its nuclear loss and apoptosis in H. pylori-infected cells. In conclusion, α-LA inhibited apoptosis induced by H. pylori by reducing ROS levels and suppressing the loss of Ku70/80 proteins in AGS cells.
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Anipindi M, Bitetto D. Diagnostic and Therapeutic Uses of the Microbiome in the Field of Oncology. Cureus 2022; 14:e24890. [PMID: 35698690 PMCID: PMC9184241 DOI: 10.7759/cureus.24890] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/08/2022] [Indexed: 11/21/2022] Open
Abstract
Cancer is a leading cause of death worldwide and it can affect almost every part of the human body. Effective screening and early diagnosis of cancers is extremely difficult due to the multifactorial etiology of the disease and delayed presentation of the patients. The available treatments are usually not specific to the affected organ system, leading to intolerable systemic side effects and early withdrawal from therapies. In vivo and in vitro studies have revealed an association of specific microbiome signatures with individual cancers. The cancer-related human microbiome has also been shown to affect the response of tissues to chemotherapy, immunotherapy, and radiation. This is an excellent opportunity for us to design specific screening markers using the microbiome to prevent cancers and diagnose them early. We can also develop precise treatments that can target cancer-affected specific organ systems and probably use a lesser dose of chemotherapy or radiation for the same effect. This prevents adverse effects and early cessation of treatments. However, we need further studies to exactly clarify and characterize these associations. In this review article, we focus on the association of the microbiome with individual cancers and highlight its future role in cancer screenings, diagnosis, prognosis, and treatments.
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Affiliation(s)
- Manasa Anipindi
- Internal Medicine, Einstein Medical Center Philadelphia, East Norriton, USA
| | - Daniel Bitetto
- Internal Medicine, Einstein Medical Center Philadelphia, East Norriton, USA
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39
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Wang Y, Li H. Gut microbiota modulation: a tool for the management of colorectal cancer. J Transl Med 2022; 20:178. [PMID: 35449107 PMCID: PMC9022293 DOI: 10.1186/s12967-022-03378-8] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2022] [Accepted: 04/03/2022] [Indexed: 12/19/2022] Open
Abstract
Colorectal cancer (CRC) is the second cause of cancer death and the third most frequently diagnosed cancer. Besides the lifestyle, genetic and epigenetic alterations, and environmental factors, gut microbiota also plays a vital role in CRC development. The interruption of the commensal relationship between gut microbiota and the host could lead to an imbalance in the bacteria population, in which the pathogenic bacteria become the predominant population in the gut. Different therapeutic strategies have been developed to modify the gut immune system, prevent pathogen colonization, and alter the activity and composition of gut microbiota, such as prebiotics, probiotics, postbiotics, antibiotics, and fecal microbiota transplantation (FMT). Even though the employed strategies exhibit promising results, their translation into the clinic requires evaluating potential implications and risks, as well as assessment of their long-term effects. This study was set to review the gut microbiota imbalances and their relationship with CRC and their effects on CRC therapy, including chemotherapy and immunotherapy. More importantly, we reviewed the strategies that have been used to modulate gut microbiota, their impact on the treatment of CRC, and the challenges of each strategy.
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Affiliation(s)
- Yan Wang
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110004, China
| | - Hui Li
- Department of Gastroenterology, Shengjing Hospital of China Medical University, Shenyang, 110004, China.
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40
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Nabavi-Rad A, Azizi M, Jamshidizadeh S, Sadeghi A, Aghdaei HA, Yadegar A, Zali MR. The Effects of Vitamins and Micronutrients on Helicobacter pylori Pathogenicity, Survival, and Eradication: A Crosstalk between Micronutrients and Immune System. J Immunol Res 2022; 2022:4713684. [PMID: 35340586 PMCID: PMC8942682 DOI: 10.1155/2022/4713684] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2022] [Revised: 02/19/2022] [Accepted: 02/25/2022] [Indexed: 12/11/2022] Open
Abstract
Helicobacter pylori as a class I carcinogen is correlated with a variety of severe gastroduodenal diseases; therefore, H. pylori eradication has become a priority to prevent gastric carcinogenesis. However, due to the emergence and spread of multidrug and single drug resistance mechanisms in H. pylori, as well as serious side effects of currently used antibiotic interventions, achieving successful H. pylori eradication has become exceedingly difficult. Recent studies expressed the intention of seeking novel strategies to improve H. pylori management and reduce the risk of H. pylori-associated intestinal and extragastrointestinal disorders. For which, vitamin supplementation has been demonstrated in many studies to have a tight interaction with H. pylori infection, either directly through the regulation of the host inflammatory pathways or indirectly by promoting the host immune response. On the other hand, H. pylori infection is reported to result in micronutrient malabsorption or deficiency. Furthermore, serum levels of particular micronutrients, especially vitamin D, are inversely correlated to the risk of H. pylori infection and eradication failure. Accordingly, vitamin supplementation might increase the efficiency of H. pylori eradication and reduce the risk of drug-related adverse effects. Therefore, this review aims at highlighting the regulatory role of micronutrients in H. pylori-induced host immune response and their potential capacity, as intrinsic antioxidants, for reducing oxidative stress and inflammation. We also discuss the uncovered mechanisms underlying the molecular and serological interactions between micronutrients and H. pylori infection to present a perspective for innovative in vitro investigations, as well as novel clinical implications.
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Affiliation(s)
- Ali Nabavi-Rad
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahsa Azizi
- Foodborne and Waterborne Diseases Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Jamshidizadeh
- 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
| | - Hamid Asadzadeh Aghdaei
- Basic and Molecular Epidemiology of Gastrointestinal Disorders Research Center, Research Institute for Gastroenterology and Liver Diseases, Shahid Beheshti University of Medical Sciences, 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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41
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Yang H, Hu B. Immunological Perspective: Helicobacter pylori Infection and Gastritis. Mediators Inflamm 2022; 2022:2944156. [PMID: 35300405 PMCID: PMC8923794 DOI: 10.1155/2022/2944156] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2022] [Accepted: 03/02/2022] [Indexed: 02/07/2023] Open
Abstract
Helicobacter pylori is a spiral-shaped gram-negative bacterium. Its infection is mainly transmitted via oral-oral and fecal-oral routes usually during early childhood. It can achieve persistent colonization by manipulating the host immune responses, which also causes mucosal damage and inflammation. H. pylori gastritis is an infectious disease and results in chronic gastritis of different severity in near all patients with infection. It may develop from acute/chronic inflammation, chronic atrophic gastritis, intestinal metaplasia, dysplasia, and intraepithelial neoplasia, eventually to gastric cancer. This review attempts to cover recent studies which provide important insights into how H. pylori causes chronic inflammation and what the characteristic is, which will immunologically explain H. pylori gastritis.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
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Ariyoshi T, Hagihara M, Takahashi M, Mikamo H. Effect of Clostridium butyricum on Gastrointestinal Infections. Biomedicines 2022; 10:483. [PMID: 35203691 PMCID: PMC8962260 DOI: 10.3390/biomedicines10020483] [Citation(s) in RCA: 38] [Impact Index Per Article: 12.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/20/2022] [Revised: 02/13/2022] [Accepted: 02/15/2022] [Indexed: 02/01/2023] Open
Abstract
Clostridium butyricum is a human commensal bacterium with beneficial effects including butyrate production, spore formation, increasing levels of beneficial bacteria, and inhibition of pathogenic bacteria. Owing to its preventive and ameliorative effects on gastrointestinal infections, C. butyricum MIYAIRI 588 (CBM 588) has been used as a probiotic in clinical and veterinary medicine for decades. This review summarizes the effects of C. butyricum, including CBM 588, on bacterial gastrointestinal infections. Further, the characteristics of the causative bacteria, examples of clinical and veterinary use, and mechanisms exploited in basic research are presented. C. butyricum is widely effective against Clostoridioides difficile, the causative pathogen of nosocomial infections; Helicobacter pylori, the causative pathogen of gastric cancer; and antibiotic-resistant Escherichia coli. Accordingly, its mechanism is gradually being elucidated. As C. butyricum is effective against gastrointestinal infections caused by antibiotics-induced dysbiosis, it can inhibit the transmission of antibiotic-resistant genes and maintain homeostasis of the gut microbiome. Altogether, C. butyricum is expected to be one of the antimicrobial-resistance (AMR) countermeasures for the One-health approach.
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Affiliation(s)
- Tadashi Ariyoshi
- Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Aichi, Japan; (T.A.); (M.H.); (M.T.)
- Miyarisan Pharmaceutical Co., Ltd., Saitama City 331-0804, Saitama, Japan
| | - Mao Hagihara
- Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Aichi, Japan; (T.A.); (M.H.); (M.T.)
- Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute 480-1195, Aichi, Japan
| | - Motomichi Takahashi
- Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Aichi, Japan; (T.A.); (M.H.); (M.T.)
- Miyarisan Pharmaceutical Co., Ltd., Saitama City 331-0804, Saitama, Japan
| | - Hiroshige Mikamo
- Department of Clinical Infectious Diseases, Aichi Medical University, Nagakute 480-1195, Aichi, Japan; (T.A.); (M.H.); (M.T.)
- Department of Molecular Epidemiology and Biomedical Sciences, Aichi Medical University, Nagakute 480-1195, Aichi, Japan
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Tortora SC, Bodiwala VM, Quinn A, Martello LA, Vignesh S. Microbiome and colorectal carcinogenesis: Linked mechanisms and racial differences. World J Gastrointest Oncol 2022; 14:375-395. [PMID: 35317317 PMCID: PMC8918999 DOI: 10.4251/wjgo.v14.i2.375] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/26/2021] [Accepted: 01/14/2022] [Indexed: 02/06/2023] Open
Abstract
Various studies have shown the interplay between the intestinal microbiome, environmental factors, and genetic changes in colorectal cancer (CRC) development. In this review, we highlight the various gut and oral microbiota associated with CRC and colorectal adenomas, and their proposed molecular mechanisms in relation to the processes of “the hallmarks of cancer”, and differences in microbial diversity and abundance between race/ethnicity. Patients with CRC showed increased levels of Bacteroides, Prevotella, Escherichia coli, enterotoxigenic Bacteroides fragilis, Streptococcus gallolyticus, Enterococcus faecalis, Fusobacterium nucleatum (F. nucleatum) and Clostridium difficile. Higher levels of Bacteroides have been found in African American (AA) compared to Caucasian American (CA) patients. Pro-inflammatory bacteria such as F. nucleatum and Enterobacter species were significantly higher in AAs. Also, AA patients have been shown to have decreased microbial diversity compared to CA patients. Some studies have shown that using microbiome profiles in conjunction with certain risk factors such as age, race and body mass index may help predict healthy colon vs one with adenomas or carcinomas. Periodontitis is one of the most common bacterial infections in humans and is more prevalent in Non-Hispanic-Blacks as compared to Non-Hispanic Whites. This condition causes increased systemic inflammation, immune dysregulation, gut microbiota dysbiosis and thereby possibly influencing colorectal carcinogenesis. Periodontal-associated bacteria such as Fusobacterium, Prevotella, Bacteroides and Porphyromonas have been found in CRC tissues and in feces of CRC patients. Therefore, a deeper understanding of the association between oral and gastrointestinal bacterial profile, in addition to identifying prevalent bacteria in patients with CRC and the differences observed in ethnicity/race, may play a pivotal role in predicting incidence, prognosis, and lead to the development of new treatments.
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Affiliation(s)
- Sofia C Tortora
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Vimal M Bodiwala
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Andrew Quinn
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Laura A Martello
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
| | - Shivakumar Vignesh
- Department of Medicine and Division of Gastroenterology & Hepatology, SUNY Downstate Health Sciences University, Brooklyn, NY 11203, United States
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Yang H, Wei B, Hu B. Chronic inflammation and long-lasting changes in the gastric mucosa after Helicobacter pylori infection involved in gastric cancer. Inflamm Res 2021; 70:1015-1026. [PMID: 34549319 DOI: 10.1007/s00011-021-01501-x] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2021] [Revised: 07/13/2021] [Accepted: 09/09/2021] [Indexed: 02/07/2023] Open
Abstract
OBJECTIVE Helicobacter pylori (H. pylori) infects approximately half of the world's population, as one of the most common chronic infections. H. pylori infection has been widely recognized as a major risk factor for gastric cancer (GC). METHODS Eradication treatment is considered to abolish the inflammatory response and prevent progression to GC. However, only 1-3% of H. pylori-infected patients develop GC, whereas GC can occur even after eradicating H. pylori. In addition, the incidence of GC following H. pylori infection is significantly higher compared to the gross incidence induced by all causes, although eradicating H. pylori reduces the risk of developing GC. RESULTS Therefore, it is reasonable to hypothesize that H. pylori infection results in changes that persist even after its eradication. Several of these changes may not be reversible within a short time, including the status of inflammation, the dysfunction of immunity and apoptosis, mitochondrial changes, aging and gastric dysbacteriosis. CONCLUSION The present review article aimed to discuss these potential long-lasting changes induced by H. pylori infection that may follow the eradication of H. pylori and contribute to the development of GC.
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Affiliation(s)
- Hang Yang
- Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China
| | - Bin Wei
- Department of Gastroenterology, The First Hospital of Xi'an City, Xi'an, 710002, Shanxi, People's Republic of China
| | - Bing Hu
- Department of Gastroenterology, West China Hospital, Sichuan University, 37 Guo Xue Xiang, Chengdu, 610041, Sichuan, People's Republic of China.
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Helicobacter pylori FabX contains a [4Fe-4S] cluster essential for unsaturated fatty acid synthesis. Nat Commun 2021; 12:6932. [PMID: 34836944 PMCID: PMC8626469 DOI: 10.1038/s41467-021-27148-0] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2021] [Accepted: 10/29/2021] [Indexed: 11/08/2022] Open
Abstract
Unsaturated fatty acids (UFAs) are essential for functional membrane phospholipids in most bacteria. The bifunctional dehydrogenase/isomerase FabX is an essential UFA biosynthesis enzyme in the widespread human pathogen Helicobacter pylori, a bacterium etiologically related to 95% of gastric cancers. Here, we present the crystal structures of FabX alone and in complexes with an octanoyl-acyl carrier protein (ACP) substrate or with holo-ACP. FabX belongs to the nitronate monooxygenase (NMO) flavoprotein family but contains an atypical [4Fe-4S] cluster absent in all other family members characterized to date. FabX binds ACP via its positively charged α7 helix that interacts with the negatively charged α2 and α3 helices of ACP. We demonstrate that the [4Fe-4S] cluster potentiates FMN oxidation during dehydrogenase catalysis, generating superoxide from an oxygen molecule that is locked in an oxyanion hole between the FMN and the active site residue His182. Both the [4Fe-4S] and FMN cofactors are essential for UFA synthesis, and the superoxide is subsequently excreted by H. pylori as a major resource of peroxide which may contribute to its pathogenic function in the corrosion of gastric mucosa.
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Alexander SM, Retnakumar RJ, Chouhan D, Devi TNB, Dharmaseelan S, Devadas K, Thapa N, Tamang JP, Lamtha SC, Chattopadhyay S. Helicobacter pylori in Human Stomach: The Inconsistencies in Clinical Outcomes and the Probable Causes. Front Microbiol 2021; 12:713955. [PMID: 34484153 PMCID: PMC8416104 DOI: 10.3389/fmicb.2021.713955] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2021] [Accepted: 07/20/2021] [Indexed: 12/11/2022] Open
Abstract
Pathogenic potentials of the gastric pathogen, Helicobacter pylori, have been proposed, evaluated, and confirmed by many laboratories for nearly 4 decades since its serendipitous discovery in 1983 by Barry James Marshall and John Robin Warren. Helicobacter pylori is the first bacterium to be categorized as a definite carcinogen by the International Agency for Research on Cancer (IARC) of the World Health Organization (WHO). Half of the world’s population carries H. pylori, which may be responsible for severe gastric diseases like peptic ulcer and gastric cancer. These two gastric diseases take more than a million lives every year. However, the role of H. pylori as sole pathogen in gastric diseases is heavily debated and remained controversial. It is still not convincingly understood, why most (80–90%) H. pylori infected individuals remain asymptomatic, while some (10–20%) develop such severe gastric diseases. Moreover, several reports indicated that colonization of H. pylori has positive and negative associations with several other gastrointestinal (GI) and non-GI diseases. In this review, we have discussed the state of the art knowledge on “H. pylori factors” and several “other factors,” which have been claimed to have links with severe gastric and duodenal diseases. We conclude that H. pylori infection alone does not satisfy the “necessary and sufficient” condition for developing aggressive clinical outcomes. Rather, the cumulative effect of a number of factors like the virulence proteins of H. pylori, local geography and climate, genetic background and immunity of the host, gastric and intestinal microbiota, and dietary habit and history of medicine usage together determine whether the H. pylori infected person will remain asymptomatic or will develop one of the severe gastric diseases.
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Affiliation(s)
| | | | - Deepak Chouhan
- Rajiv Gandhi Centre for Biotechnology, Trivandrum, India.,Centre for Doctoral Studies, Manipal Academy of Higher Education, Manipal, India
| | | | | | - Krishnadas Devadas
- Department of Gastroenterology, Government Medical College, Trivandrum, India
| | - Namrata Thapa
- Biotech Hub, Department of Zoology, Nar Bahadur Bhandari Degree College, Gangtok, India
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Non-Coding RNAs and Reactive Oxygen Species–Symmetric Players of the Pathogenesis Associated with Bacterial and Viral Infections. Symmetry (Basel) 2021. [DOI: 10.3390/sym13071307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022] Open
Abstract
Infections can be triggered by a wide range of pathogens. However, there are few strains of bacteria that cause illness, but some are quite life-threatening. Likewise, viral infections are responsible for many human diseases, usually characterized by high contagiousness. Hence, as bacterial and viral infections can both cause similar symptoms, it can be difficult to determine the exact cause of a specific infection, and this limitation is critical. However, recent scientific advances have geared us up with the proper tools required for better diagnoses. Recent discoveries have confirmed the involvement of non-coding RNAs (ncRNAs) in regulating the pathogenesis of certain bacterial or viral infections. Moreover, the presence of reactive oxygen species (ROS) is also known as a common infection trait that can be used to achieve a more complete description of such pathogen-driven conditions. Thus, this opens further research opportunities, allowing scientists to explore infection-associated genetic patterns and develop better diagnosis and treatment methods. Therefore, the aim of this review is to summarize the current knowledge of the implication of ncRNAs and ROS in bacterial and viral infections, with great emphasis on their symmetry but, also, on their main differences.
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Wang Z, Cong TD, Zhong W, Lau JW, Kwek G, Chan-Park MB, Xing B. Cyanine-Dyad Molecular Probe for the Simultaneous Profiling of the Evolution of Multiple Radical Species During Bacterial Infections. Angew Chem Int Ed Engl 2021; 60:16900-16905. [PMID: 34018295 DOI: 10.1002/anie.202104100] [Citation(s) in RCA: 48] [Impact Index Per Article: 12.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2021] [Revised: 05/12/2021] [Indexed: 12/16/2022]
Abstract
Real-time monitoring of the evolution of bacterial infection-associated multiple radical species is critical to accurately profile the pathogenesis and host-defense mechanisms. Here, we present a unique dual wavelength near-infrared (NIR) cyanine-dyad molecular probe (HCy5-Cy7) for simultaneous monitoring of reactive oxygen and nitrogen species (RONS) variations both in vitro and in vivo. HCy5-Cy7 specifically turns on its fluorescence at 660 nm via superoxide or hydroxyl radical (O2 .- , . OH)-mediated oxidation of reduced HCy5 moiety to Cy5, while peroxynitrite or hypochlorous species (ONOO- , ClO- )-induced Cy7 structural degradation causes the emission turn-off at 800 nm. Such multispectral but reverse signal responses allow multiplex manifestation of in situ oxidative and nitrosative stress events during the pathogenic and defensive processes in both bacteria-infected macrophage cells and living mice. Most importantly, this study may also provide new perspectives for understanding the bacterial pathogenesis and advancing the precision medicine against infectious diseases.
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Affiliation(s)
- Zhimin Wang
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang link, 637371, Singapore, Singapore
| | - Thang Do Cong
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang link, 637371, Singapore, Singapore
| | - Wenbin Zhong
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore, Singapore
| | - Jun Wei Lau
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang link, 637371, Singapore, Singapore
| | - Germain Kwek
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang link, 637371, Singapore, Singapore
| | - Mary B Chan-Park
- School of Chemical and Biomedical Engineering, Nanyang Technological University, 62 Nanyang Drive, 637459, Singapore, Singapore
| | - Bengang Xing
- Division of Chemistry and Biological Chemistry, School of Physical & Mathematical Sciences, Nanyang Technological University, 21 Nanyang link, 637371, Singapore, Singapore.,School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, 637459, Singapore, Singapore
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Wang Z, Cong TD, Zhong W, Lau JW, Kwek G, Chan‐Park MB, Xing B. Cyanine‐Dyad Molecular Probe for the Simultaneous Profiling of the Evolution of Multiple Radical Species During Bacterial Infections. Angew Chem Int Ed Engl 2021. [DOI: 10.1002/ange.202104100] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Affiliation(s)
- Zhimin Wang
- Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University 21 Nanyang link 637371 Singapore Singapore
| | - Thang Do Cong
- Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University 21 Nanyang link 637371 Singapore Singapore
| | - Wenbin Zhong
- School of Chemical and Biomedical Engineering Nanyang Technological University 62 Nanyang Drive 637459 Singapore Singapore
| | - Jun Wei Lau
- Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University 21 Nanyang link 637371 Singapore Singapore
| | - Germain Kwek
- Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University 21 Nanyang link 637371 Singapore Singapore
| | - Mary B. Chan‐Park
- School of Chemical and Biomedical Engineering Nanyang Technological University 62 Nanyang Drive 637459 Singapore Singapore
| | - Bengang Xing
- Division of Chemistry and Biological Chemistry School of Physical & Mathematical Sciences Nanyang Technological University 21 Nanyang link 637371 Singapore Singapore
- School of Chemical and Biomedical Engineering Nanyang Technological University 70 Nanyang Drive 637459 Singapore Singapore
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Yang J, Zhou X, Liu X, Ling Z, Ji F. Role of the Gastric Microbiome in Gastric Cancer: From Carcinogenesis to Treatment. Front Microbiol 2021; 12:641322. [PMID: 33790881 PMCID: PMC8005548 DOI: 10.3389/fmicb.2021.641322] [Citation(s) in RCA: 40] [Impact Index Per Article: 10.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 02/22/2021] [Indexed: 01/10/2023] Open
Abstract
The development of sequencing technology has expanded our knowledge of the human gastric microbiome, which is now known to play a critical role in the maintenance of homeostasis, while alterations in microbial community composition can promote the development of gastric diseases. Recently, carcinogenic effects of gastric microbiome have received increased attention. Gastric cancer (GC) is one of the most common malignancies worldwide with a high mortality rate. Helicobacter pylori is a well-recognized risk factor for GC. More than half of the global population is infected with H. pylori, which can modulate the acidity of the stomach to alter the gastric microbiome profile, leading to H. pylori-associated diseases. Moreover, there is increasing evidence that bacteria other than H. pylori and their metabolites also contribute to gastric carcinogenesis. Therefore, clarifying the contribution of the gastric microbiome to the development and progression of GC can lead to improvements in prevention, diagnosis, and treatment. In this review, we discuss the current state of knowledge regarding changes in the microbial composition of the stomach caused by H. pylori infection, the carcinogenic effects of H. pylori and non-H. pylori bacteria in GC, as well as the potential therapeutic role of gastric microbiome in H. pylori infection and GC.
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Affiliation(s)
- Jinpu Yang
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xinxin Zhou
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Xiaosun Liu
- Department of Gastrointestinal Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Zongxin Ling
- Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Feng Ji
- Department of Gastroenterology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, China
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