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Pu S, Zhuang Z, Liu N, Luo Q, Zhang D. Research progress on the relationship between Helicobacter pylori infection and iron deficiency anemia. Front Microbiol 2025; 16:1552630. [PMID: 40201441 PMCID: PMC11975960 DOI: 10.3389/fmicb.2025.1552630] [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: 12/28/2024] [Accepted: 03/11/2025] [Indexed: 04/10/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection affects around half of the global population and is a globally highly prevalent pathogen that is closely linked not only to gastrointestinal diseases such as chronic atrophic gastritis, functional dyspepsia and peptic ulcer but also to the development and progression of a variety of extra-gastrointestinal diseases. Numerous studies have shown the correlation between H. pylori infection and iron-deficiency anemia (IDA). The prevalence of H. pylori infection is higher in individuals with IDA, and the hemoglobin level of patients with IDA can be increased to different degrees or even returned to normal following active H. pylori eradication. However, this conclusion is still controversial. In this paper, a comprehensive literature search was conducted using the PubMed/MEDLINE/Web of Science database, combining the following terms: "Helicobacter pylori," "Helicobacter pylori infection," "iron deficiency anemia," "iron deficiency," "iron absorption," "iron malabsorption," "serum iron," "hemoglobin," "pathogenesis," "mechanism," and "eradication therapy." Through extensive literature searches, the correlation between H. pylori infection and IDA, its potential mechanism, and the efficacy of H. pylori eradication therapy in IDA patients have been comprehensively discussed. We conclude that the majority of existing studies have confirmed the correlation between H. pylori infection and IDA, indicating that patients with H. pylori infection are more likely to develop IDA and that the prevalence of H. pylori infection is higher in individuals with IDA. Compared with iron supplementation alone, combining H. pylori eradication with iron supplementation is more effective in treating IDA, particularly in unexplained or refractory IDA cases. These findings provide valuable insights for clinicians managing patients with unexplained or refractory IDA.
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Affiliation(s)
- Sugui Pu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, China
| | - Ze Zhuang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, China
| | - Na Liu
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, China
| | - Qian Luo
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, China
| | - Dekui Zhang
- Department of Gastroenterology, The Second Clinical Medical College of Lanzhou University, Lanzhou University Second Hospital, Lanzhou, China
- Key Laboratory of Digestive Diseases, Lanzhou University Second Hospital, Lanzhou, China
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Zhang S, Huang J, Jiang Z, Tong H, Ma X, Liu Y. Tumor microbiome: roles in tumor initiation, progression, and therapy. MOLECULAR BIOMEDICINE 2025; 6:9. [PMID: 39921821 PMCID: PMC11807048 DOI: 10.1186/s43556-025-00248-9] [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: 08/02/2024] [Revised: 01/06/2025] [Accepted: 01/21/2025] [Indexed: 02/10/2025] Open
Abstract
Over the past few years, the tumor microbiome is increasingly recognized for its multifaceted involvement in cancer initiation, progression, and metastasis. With the application of 16S ribosomal ribonucleic acid (16S rRNA) sequencing, the intratumoral microbiome, also referred to as tumor-intrinsic or tumor-resident microbiome, has also been found to play a significant role in the tumor microenvironment (TME). Understanding their complex functions is critical for identifying new therapeutic avenues and improving treatment outcomes. This review first summarizes the origins and composition of these microbial communities, emphasizing their adapted diversity across a diverse range of tumor types and stages. Moreover, we outline the general mechanisms by which specific microbes induce tumor initiation, including the activation of carcinogenic pathways, deoxyribonucleic acid (DNA) damage, epigenetic modifications, and chronic inflammation. We further propose the tumor microbiome may evade immunity and promote angiogenesis to support tumor progression, while uncovering specific microbial influences on each step of the metastatic cascade, such as invasion, circulation, and seeding in secondary sites. Additionally, tumor microbiome is closely associated with drug resistance and influences therapeutic efficacy by modulating immune responses, drug metabolism, and apoptotic pathways. Furthermore, we explore innovative microbe-based therapeutic strategies, such as engineered bacteria, oncolytic virotherapy, and other modalities aimed at enhancing immunotherapeutic efficacy, paving the way for microbiome-centered cancer treatment frameworks.
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Affiliation(s)
- Shengxin Zhang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Jing Huang
- Department of Medical Ultrasound, West China Hospital of Sichuan University, 37 Guoxue Lane, Wuhou District, Chengdu, 610041, Sichuan Province, China
| | - Zedong Jiang
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Huan Tong
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China
| | - Xuelei Ma
- Department of Biotherapy, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan Province, China.
| | - Yang Liu
- Day Surgery Center, General Practice Medical Center, West China Hospital, Sichuan University, Chengdu, Sichuan, 610041, P. R. China.
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Wang Y, Cao X, Shan B, Chen S, Li S, Fei S, Pang X. Hp eradication decreased the expression level of PG II in patients of Hp negative with gastric intestinal metaplasia: a retrospective cross-sectional study. JOURNAL OF HEALTH, POPULATION, AND NUTRITION 2025; 44:20. [PMID: 39856761 PMCID: PMC11762886 DOI: 10.1186/s41043-025-00756-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/10/2024] [Accepted: 01/15/2025] [Indexed: 01/27/2025]
Abstract
AIMS This study aims to assess the serum levels of pepsinogen (PG)I, PG II, and gastrin (G17) in patients with gastric intestinal metaplasia (GIM) and evaluate their correlation with demographic characteristics. METHODS A total of 247 normal controls (NC) and 240 patients diagnosed with GIM were enrolled in this study. All participants underwent a gastroscopy procedure followed by pathological examination for diagnosis confirmation. The expression level of PGI, PG II, and G 17 was detected by fluorescence immunochromatography and Hp infection was detected by 13-carbon breath test. The demographic characteristics of the subjects were obtained through questionnaires. RESULTS Compared to the NC group, the GIM group showed a reduction in PG II expression level [10.71(6.40,16.89) VS 9.21(6.14,14.55), p = 0.010]. GIM patients had a higher prevalence of previous Hp eradication history (14.98% VS 23.75%, p = 0.014). The low PG II group exhibited a higher incidence rate of GIM compared to the high PG II group (54.10% VS 44.44%, p = 0 0.020). In the Hp-negative(Hp-) group, there was a decrease in both PGI and PG II expression levels when compared to the Hp-positive(Hp+) group [146.73 ± 78.53 VS 125.61 ± 68.75 and 10.19(7.27, 16.58) VS 7.36(5.62,12.53), p = 0.036 and p < 0.001]. Among patients without Hp eradication history, those with low PG II levels had a higher proportion of individuals with a history of Hp eradication than those with high PG II levels (29.31% VS 3.13%, p = 0.003). Additionally, within the subgroup that underwent Hp eradication, there was a decrease in PG II expression level compared to the subgroup without Hp eradication (6.16(5.13, 7.52) VS 8.73(5.67, 13.35), p = 0.041). CONCLUSION The prevalence of GIM was significantly associated with low levels of PG II. There was a significant association between HP eradication history and the prevalence of GIM. Hp eradication history resulted in reduced expression levels of PG II in Hp- GIM patients.
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Affiliation(s)
- Yanhong Wang
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road, Xuzhou, Jiang Su, 221004, China
| | - Xixiang Cao
- Graduate school, Xuzhou Medical University, Xuzhou, 221009, China
| | - Baodong Shan
- Graduate school, Xuzhou Medical University, Xuzhou, 221009, China
| | - Song Chen
- Graduate school, Xuzhou Medical University, Xuzhou, 221009, China
| | - Shengnan Li
- Graduate school, Xuzhou Medical University, Xuzhou, 221009, China
| | - Sujuan Fei
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road, Xuzhou, Jiang Su, 221004, China.
| | - Xunlei Pang
- Department of Gastroenterology, The Affiliated Hospital of Xuzhou Medical University, Huaihai West Road, Xuzhou, Jiang Su, 221004, China.
- College of Pharmacy, Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy, Xuzhou, 221009, China.
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Zhong L, Yang Q, Shao Y, Hu S, Guo L. Helicobacter pylori promotes intestinal flora imbalance and hepatic metabolic disorders under arsenic stress. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2025; 290:117512. [PMID: 39671763 DOI: 10.1016/j.ecoenv.2024.117512] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/16/2024] [Revised: 10/21/2024] [Accepted: 12/08/2024] [Indexed: 12/15/2024]
Abstract
Environmental arsenic contamination is a serious issue that cannot be ignored, since arsenic levels in drinking water frequently exceed safety standards, and there is an increased prevalence of Helicobacter pylori (H. pylori) infection. This results in an increasing population at risk of simultaneous exposure to both harmful agents, yet whether a synergistic interaction exists between them remains unclear. Therefore, this study aims to investigate the combined effects and underlying pathogenic mechanisms of concurrent exposure to these two hazardous factors by establishing a mouse model that is infected with H. pylori and exposed to inorganic arsenic through drinking water. Analysis of intestinal flora revealed significant alterations in the composition, relative abundance (Akkermansia, Faecalibaculum, Ilieibacterium, etc.), and metabolic potential of the intestinal microflora (amino acid metabolism and energy metabolism) in the combinatory exposure group. Non-targeted metabolomics analysis identified that the combinatory exposure group exhibited greater fluctuations in metabolite content, particularly in triacylglycerol, fatty-acid, peptide and amino acid. Moreover, H. pylori infection and arsenic exposure had increased levels of metabolites associated with the intestinal microbiota in their livers (4-Ethylphenyl sulfate and Phenylacetylglycine). Further analysis revealed significant correlations between changes in the intestinal flora and alterations in liver metabolic profiles. Herein, we hypothesize that H. pylori infection may exacerbate the intestinal flora imbalance and hepatic metabolic disturbances caused by arsenic exposure, which may disrupt enterohepatic homeostasis and potentially increase biological susceptibility to heavy metal toxicity.
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Affiliation(s)
- Linmin Zhong
- Dongguan Key Laboratory of Public Health Laboratory Science, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University, Dongguan 523808, China
| | - Qiling Yang
- Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Yiming Shao
- Dongguan Key Laboratory of Sepsis Translational Medicine, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan 523808, China
| | - Shanwen Hu
- Department of Health Inspection and Quarantine, School of Public Health, Fujian Medical University, Fuzhou 350122, China
| | - Lianxian Guo
- Dongguan Key Laboratory of Public Health Laboratory Science, The First Dongguan Affiliated Hospital, School of Public Health, Guangdong Medical University, Dongguan 523808, China.
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Heidary M, Akrami S, Madanipour T, Shakib NH, Mahdizade Ari M, Beig M, Khoshnood S, Ghanavati R, Bazdar M. Effect of Helicobacter pylori-induced gastric cancer on gastrointestinal microbiota: a narrative review. Front Oncol 2025; 14:1495596. [PMID: 39868371 PMCID: PMC11757270 DOI: 10.3389/fonc.2024.1495596] [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: 09/12/2024] [Accepted: 12/12/2024] [Indexed: 01/28/2025] Open
Abstract
Helicobacter pylori (H. pylori) infection is a typical microbial agent that interferes with the complex mechanisms of gastric homeostasis by disrupting the balance between the host gastric microbiota and mucosa-related factors, ultimately leading to inflammatory changes, dysbiosis, and gastric cancer (GC). We searched this field on the basis of PubMed, Google Scholar, Web of Science, and Scopus databases. Most studies show that H. pylori inhibits the colonization of other bacteria, resulting in a less variety of bacteria in the gastrointestinal (GI) tract. When comparing the patients with H. pylori-positive and H. pylori-negative GC, the composition of the gastric microbiome changes with increasing abundance of H. pylori (where present) in the gastritis stage, whereas, as the gastric carcinogenesis cascade progresses to GC, oral and intestinal-type pathogenic microbial strains predominate. H. pylori infection induces a premalignant milieu of atrophy and intestinal metaplasia, and the resulting change in gastric microbiota appears to play an important role in gastric carcinogenesis. The effect of H. pylori-induced GC on GI microbiota is discussed in this review.
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Affiliation(s)
- Mohsen Heidary
- Leishmaniasis Research Center, Sabzevar University of Medical Sciences, Sabzevar, Iran
| | - Sousan Akrami
- Department of Microbiology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
| | - Tohid Madanipour
- Department of Microbiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Nafiseh Hosseinzadeh Shakib
- Department of Bacteriology and Virology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Marzie Mahdizade Ari
- Department of Microbiology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran
| | - Masoumeh Beig
- Department of Bacteriology, Pasteur Institute of Iran, Tehran, Iran
| | - Saeed Khoshnood
- Clinical Microbiology Research Center, Ilam University of Medical Sciences, Ilam, Iran
| | - Roya Ghanavati
- School of Medicine, Behbahan Faculty of Medical Sciences, Behbahan, Iran
| | - Monireh Bazdar
- School of Medicine, Razi Hospital, Ilam University of Medical Sciences, Ilam, Iran
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Ye C, Liu X, Liu Z, Pan C, Zhang X, Zhao Z, Sun H. Fusobacterium nucleatum in tumors: from tumorigenesis to tumor metastasis and tumor resistance. Cancer Biol Ther 2024; 25:2306676. [PMID: 38289287 PMCID: PMC10829845 DOI: 10.1080/15384047.2024.2306676] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 01/13/2024] [Indexed: 02/01/2024] Open
Abstract
Fusobacterium nucleatum, an anaerobic Gram-negative bacterium primarily residing in the oral cavity, has garnered significant attention for its emerging role in cancer progression and prognosis. While extensive research has revealed mechanistic links between Fusobacterium nucleatum and colorectal cancer, a comprehensive review spanning its presence and metastatic implications in cancers beyond colorectal origin is conspicuously absent. This paper broadens our perspective from colorectal cancer to various malignancies associated with Fusobacterium nucleatum, including oral, pancreatic, esophageal, breast, and gastric cancers. Our central focus is to unravel the mechanisms governing Fusobacterium nucleatum colonization, initiation, and promotion of metastasis across diverse cancer types. Additionally, we explore Fusobacterium nucleatum's adverse impacts on cancer therapies, particularly within the domains of immunotherapy and chemotherapy. Furthermore, this paper underscores the clinical research significance of Fusobacterium nucleatum as a potential tumor biomarker and therapeutic target, offering a novel outlook on its applicability in cancer detection and prognostic assessment.
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Affiliation(s)
- Chun Ye
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiao Liu
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zilun Liu
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Chuxuan Pan
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Xiaowei Zhang
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Zhanyi Zhao
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
| | - Haitao Sun
- Clinical Biobank Center, Microbiome Medicine Center, Department of Laboratory Medicine, Zhujiang Hospital, The Second School of Clinical Medicine, Southern Medical University, Guangzhou, China
- Department of Laboratory Medicine, Central People’s Hospital of Ji’an, Shanghai East Hospital of Ji’an, Ji’an, China
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Xie L, Liu GW, Liu YN, Li PY, Hu XN, He XY, Huan RB, Zhao TL, Guo HJ. Prevalence of Helicobacter pylori infection in China from 2014-2023: A systematic review and meta-analysis. World J Gastroenterol 2024; 30:4636-4656. [PMID: 39575409 PMCID: PMC11572641 DOI: 10.3748/wjg.v30.i43.4636] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/03/2024] [Revised: 09/19/2024] [Accepted: 10/16/2024] [Indexed: 10/31/2024] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) stands as the predominant infectious agent linked to the onset of gastritis, peptic ulcer diseases, and gastric cancer (GC). Identified as the exclusive bacterial factor associated with the onset of GC, it is classified as a group 1 carcinogen by the World Health Organization. The elimination of H. pylori plays a crucial role in the primary prevention of GC. While the prevalence has declined in recent decades, H. pylori infection is still highly prevalent in China, accounting for a significant part of the disease burden of GC. Therefore, updated prevalence information for H. pylori infection, especially regional and demographic variations in China, is an important basis for the design of targeted strategies that will be effective for the prevention of GC and application of policies for H. pylori control. AIM To methodically evaluate the occurrence of H. pylori infection throughout China and establish a reference point for subsequent investigations. METHODS A systematic review and meta-analysis was conducted following established guidelines, as detailed in our methodology section. RESULTS Our review synthesized data from 152 studies, covering a sample of 763827 individuals, 314423 of whom were infected with H. pylori. We evaluated infection rates in mainland China and the combined prevalence of H. pylori was 42.8% (95%CI: 40.7-44.9). Subgroup analysis indicated the highest prevalence in Northwest China at 51.3% (95%CI: 45.6-56.9), and in Qinghai Province, the prevalence reached 60.2% (95%CI: 46.5-73.9). The urea breath test, which recorded the highest infection rate, showed a prevalence of 43.7% (95%CI: 41.4-46.0). No notable differences in infection rates were observed between genders. Notably, the prevalence among the elderly was significantly higher at 44.5% (95%CI: 41.9-47.1), compared to children, who showed a prevalence of 27.5% (95%CI: 19.58-34.7). CONCLUSION Between 2014 and 2023, the prevalence of H. pylori infection in China decreased to 42.8%, down from the previous decade. However, the infection rates vary considerably across different geographical areas, among various populations, and by detection methods employed.
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Affiliation(s)
- Lu Xie
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Guang-Wei Liu
- Department of Spleen, Stomach, Liver and Gallbladder, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Ya-Nan Liu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Peng-Yu Li
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
| | - Xin-Ning Hu
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Xin-Yi He
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Rui-Bo Huan
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Tai-Long Zhao
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou 450046, Henan Province, China
| | - Hui-Jun Guo
- Department of Acquired Immune Deficiency Syndrome Treatment and Research Center, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
- Henan Key Laboratory of Viral Diseases Prevention and Treatment of Chinese Medicine, Henan University of Chinese Medicine, Zhengzhou 450000, Henan Province, China
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Bawali P, Brahma A, Rana SR, Pal A, Bhattacharyya A. Helicobacter pylori infection and inflammatory events: the extracellular vesicle-connect in driving gastrointestinal tract cancers. Front Med (Lausanne) 2024; 11:1444242. [PMID: 39610678 PMCID: PMC11602329 DOI: 10.3389/fmed.2024.1444242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2024] [Accepted: 10/28/2024] [Indexed: 11/30/2024] Open
Affiliation(s)
| | | | | | | | - Asima Bhattacharyya
- School of Biological Sciences, National Institute of Science Education and Research (NISER) Bhubaneswar, An OCC of Homi Bhabha National Institute, Khurda, Odisha, India
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Liu Y, Shang X, Du W, Shen W, Zhu Y. Helicobacter Pylori Infection as the Predominant High-Risk Factor for Gastric Cancer Recurrence Post-Gastrectomy: An 8-Year Multicenter Retrospective Study. Int J Gen Med 2024; 17:4999-5014. [PMID: 39494357 PMCID: PMC11531290 DOI: 10.2147/ijgm.s485347] [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: 07/03/2024] [Accepted: 10/24/2024] [Indexed: 11/05/2024] Open
Abstract
Purpose The reappearance of gastric cancer, a frequent postoperative complication following radical gastric cancer surgery, substantially impacts the near-term and far-reaching medical outlook of patients. The objective of this research was to create a machine learning algorithm that could recognize high-risk factors for gastric cancer recurrence and anticipate the correlation between gastric cancer recurrence and Helicobacter pylori (H. pylori) infection. Patients and Methods This investigation comprised 1234 patients diagnosed with gastric cancer, and 37 characteristic variables were obtained. Four machine learning algorithms, namely, extreme gradient boosting (XGBoost), random forest (RF), k-nearest neighbor algorithm (KNN), and multilayer perceptron (MLP), were implemented to develop the models. The k-fold cross-validation technique was utilized to perform internal validation of the four models, while independent datasets were employed for external validation of the models. Results In contrast to the other machine learning models, the XGBoost algorithm demonstrated superior predictive ability regarding high-risk factors for gastric cancer recurrence. The outcomes of Shapley additive explanation (SHAP) analysis revealed that tumor invasion depth, tumor lymph node metastasis, H. pylori infection, postoperative carcinoembryonic antigen (CEA), tumor size, and tumor number were risk elements for gastric cancer recurrence in patients, with H. pylori infection being the primary high-risk factor. Conclusion Out of the four machine learning models, the XGBoost algorithm exhibited superior performance in predicting the recurrence of gastric cancer. In addition, machine learning models can help clinicians identify key prognostic factors that are clinically meaningful for the application of personalized patient monitoring and immunotherapy.
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Affiliation(s)
- Yuan Liu
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
- Department of General Surgery, Tengzhou Central People’s Hospital, Jining Medical College, Shandong, People’s Republic of China
| | - Xingchen Shang
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Wenyi Du
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Wei Shen
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
| | - Yanfei Zhu
- Department of General Surgery, Wuxi Medical Center of Nanjing Medical University, Wuxi, People’s Republic of China
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Zeber-Lubecka N, Kulecka M, Dabrowska M, Kluska A, Piątkowska M, Turkot MH, Pilonis ND, Yusuf A, Nowicki-Osuch K, Mikula M, Ostrowski J. Dysbiosis of the Upper Gastrointestinal Tract in Head-and-Neck Cancer Survivors: A Pilot Study Using the Capsule Sponge Device. Cancers (Basel) 2024; 16:3528. [PMID: 39456621 PMCID: PMC11506215 DOI: 10.3390/cancers16203528] [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: 09/13/2024] [Revised: 10/15/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND A non-endoscopic capsule-sponge device allows sampling the entire length of the esophagus. Here, we compared microbiomes of the oral cavity, esophagus, and gastric corpus collected by oral swab, capsule-sponge device, and endoscopic biopsy, respectively, in patients representing three distinct risk profiles for esophageal squamous cell carcinoma (ESCC). METHODS The study enrolled 11 patients with esophageal squamous intraepithelial neoplasia, 21 patients after curative treatment for head and neck squamous cell cancer (HNSCC) (HNSCC survivors), and 40 patients with functional dyspeptic (FD) symptoms. Microbial genomic DNA was analyzed using 16S rRNA gene amplicon sequencing. RESULTS The Shannon index of the capsule-sponge sample microbiota was significantly higher in FD group than in patients after treatment for HNSCC, and the Chao index of gastric samples differed between HNSCC survivors and FD patients. Analysis of the β-diversity of FD patients, HNSCC, and esophageal squamous intraepithelial neoplasia showed that different genera formed at each location. The abundance of 205, 116, and 9 genera differed between FD patients and HNSCC survivors in the gastric, capsule-sponge, and oral samples, respectively; 33 genera differed between the FD group and patients with esophageal squamous intraepithelial neoplasia in capsule-sponge samples. CONCLUSIONS The bacterial communities of the upper digestive tract were clustered according to the anatomic site. Despite substantial differences in gastric and esophageal microbiota samples between FD patients and HNSCC survivors, the microbial members and diversity showed small differences between FD patients and those with esophageal squamous intraepithelial neoplasia. It remains unclear whether gastric and esophageal dysbiosis is associated with or is a consequence of treatment for HNSCC.
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Affiliation(s)
- Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Michalina Dabrowska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Anna Kluska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Magdalena Piątkowska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Maryla Helena Turkot
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Nastazja Dagny Pilonis
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Gastrointestinal Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Aisha Yusuf
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 1TN, UK;
| | | | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
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11
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Wang X, Gao X, Yu J, Zhang X, Nie Y. Emerging trends in early-onset gastric cancer. Chin Med J (Engl) 2024:00029330-990000000-01179. [PMID: 39148190 PMCID: PMC11407816 DOI: 10.1097/cm9.0000000000003259] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2024] [Indexed: 08/17/2024] Open
Abstract
ABSTRACT The incidence of early-onset gastric cancer (EOGC) is consistently increasing, and its etiology is notably complex. This increase may be attributed to distinctive factors that differ from those associated with late-onset gastric cancer (LOGC), including genetic predispositions, dietary factors, gastric microbiota dysbiosis, and screening of high-risk cases. These factors collectively contribute to the onset of cancer. EOGC significantly differs from LOGC in terms of clinicopathological and molecular characteristics. Moreover, multiple differences in prognosis and clinical management also exist. This study aimed to systematically review the latest research advancements in the epidemiological characteristics, etiological factors, clinicopathological and molecular features, prognosis, and treatment modalities of EOGC.
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Affiliation(s)
- Xinlin Wang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Xi'an, Shaanxi 710032, China
- National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Xianchun Gao
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Xi'an, Shaanxi 710032, China
- National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Jun Yu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Xi'an, Shaanxi 710032, China
- National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
| | - Xiaotian Zhang
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Xi'an, Shaanxi 710032, China
- Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Gastrointestinal Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China
| | - Yongzhan Nie
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Xi'an, Shaanxi 710032, China
- National Clinical Research Center for Digestive Diseases, Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi'an, Shaanxi 710032, China
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12
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Wang JL, Jing DD. Gastric microbiome and gastric cancer: Relationship, mechanism, and clinical significance. WORLD CHINESE JOURNAL OF DIGESTOLOGY 2024; 32:327-332. [DOI: 10.11569/wcjd.v32.i5.327] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/29/2024]
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13
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Abdullah ST, Abdullah SR, Hussen BM, Younis YM, Rasul MF, Taheri M. Role of circular RNAs and gut microbiome in gastrointestinal cancers and therapeutic targets. Noncoding RNA Res 2024; 9:236-252. [PMID: 38192436 PMCID: PMC10771991 DOI: 10.1016/j.ncrna.2023.12.002] [Citation(s) in RCA: 7] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2023] [Revised: 11/10/2023] [Accepted: 12/11/2023] [Indexed: 01/10/2024] Open
Abstract
Gastrointestinal cancers are a huge worldwide health concern, which includes a wide variety of digestive tract cancers. Circular RNAs (circRNAs), a kind of non-coding RNA (ncRNAs), are a family of single-stranded, covalently closed RNAs that have become recognized as crucial gene expression regulators, having an impact on several cellular functions in cancer biology. The gut microbiome, which consists of several different bacteria, actively contributes to the regulation of host immunity, inflammation, and metabolism. CircRNAs and the gut microbiome interact significantly to greatly affect the growth of GI cancer. Several studies focus on the complex functions of circRNAs and the gut microbiota in GI cancers, including esophageal cancer, colorectal cancer, gastric cancer, hepatocellular cancer, and pancreatic cancer. It also emphasizes how changed circRNA expression profiles and gut microbiota affect pathways connected to malignancy as well as how circRNAs affect hallmarks of gastrointestinal cancers. Furthermore, circRNAs and gut microbiota have been recommended as biological markers for therapeutic targets as well as diagnostic and prognostic purposes. Targeting circRNAs and the gut microbiota for the treatment of gastrointestinal cancers is also being continued to study. Despite significant initiatives, the connection between circRNAs and the gut microbiota and the emergence of gastrointestinal cancers remains poorly understood. In this study, we will go over the most recent studies to emphasize the key roles of circRNAs and gut microbiota in gastrointestinal cancer progression and therapeutic options. In order to create effective therapies and plan for the future gastrointestinal therapy, it is important to comprehend the functions and mechanisms of circRNAs and the gut microbiota.
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Affiliation(s)
- Sara Tharwat Abdullah
- Department of Pharmacology and Toxicology, College of Pharmacy, Hawler Medical University, Erbil, Iraq
| | - Snur Rasool Abdullah
- Medical Laboratory Science, College of Health Sciences, Lebanese French University, Kurdistan Region, Erbil, Iraq
| | - Bashdar Mahmud Hussen
- Department of Biomedical Sciences, College of Science, Cihan University-Erbil, Kurdistan Region, 44001, Iraq
- Department of Clinical Analysis, College of Pharmacy, Hawler Medical University, Kurdistan Region, Erbil, Iraq
| | - Yousif Mohammed Younis
- Department of Nursing, College of Nursing, Lebanese French University, Kurdistan Region, Erbil, Iraq
| | - Mohammed Fatih Rasul
- Department of Pharmaceutical Basic Science, Faculty of Pharmacy, Tishk International University, Erbil, Kurdistan Region, Iraq
| | - Mohammad Taheri
- Institute of Human Genetics, Jena University Hospital, Jena, Germany
- Urology and Nephrology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
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14
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Rugge M, Genta RM, Malfertheiner P, Dinis-Ribeiro M, El-Serag H, Graham DY, Kuipers EJ, Leung WK, Park JY, Rokkas T, Schulz C, El-Omar EM. RE.GA.IN.: the Real-world Gastritis Initiative-updating the updates. Gut 2024; 73:407-441. [PMID: 38383142 DOI: 10.1136/gutjnl-2023-331164] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/18/2023] [Accepted: 12/18/2023] [Indexed: 02/23/2024]
Abstract
At the end of the last century, a far-sighted 'working party' held in Sydney, Australia addressed the clinicopathological issues related to gastric inflammatory diseases. A few years later, an international conference held in Houston, Texas, USA critically updated the seminal Sydney classification. In line with these initiatives, Kyoto Global Consensus Report, flanked by the Maastricht-Florence conferences, added new clinical evidence to the gastritis clinicopathological puzzle.The most relevant topics related to the gastric inflammatory diseases have been addressed by the Real-world Gastritis Initiative (RE.GA.IN.), from disease definitions to the clinical diagnosis and prognosis. This paper reports the conclusions of the RE.GA.IN. consensus process, which culminated in Venice in November 2022 after more than 8 months of intense global scientific deliberations. A forum of gastritis scholars from five continents participated in the multidisciplinary RE.GA.IN. consensus. After lively debates on the most controversial aspects of the gastritis spectrum, the RE.GA.IN. Faculty amalgamated complementary knowledge to distil patient-centred, evidence-based statements to assist health professionals in their real-world clinical practice. The sections of this report focus on: the epidemiology of gastritis; Helicobacter pylori as dominant aetiology of environmental gastritis and as the most important determinant of the gastric oncogenetic field; the evolving knowledge on gastric autoimmunity; the clinicopathological relevance of gastric microbiota; the new diagnostic horizons of endoscopy; and the clinical priority of histologically reporting gastritis in terms of staging. The ultimate goal of RE.GA.IN. was and remains the promotion of further improvement in the clinical management of patients with gastritis.
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Affiliation(s)
- Massimo Rugge
- Department of Medicine-DIMED, University of Padova, Padua, Italy
- Azienda Zero, Veneto Tumour Registry, Padua, Italy
| | - Robert M Genta
- Gastrointestinal Pathology, Inform Diagnostics Research Institute, Dallas, Texas, USA
- Pathology, Baylor College of Medicine, Houston, Texas, USA
| | - Peter Malfertheiner
- Medizinische Klinik und Poliklinik II, Ludwig Maximilian Universität Klinikum München, Munich, Germany
- Klinik für Gastroenterologie, Hepatologie und Infektiologie, Otto-von-Guericke Universität Magdeburg, Magdeburg, Germany
| | - Mario Dinis-Ribeiro
- Porto Comprehensive Cancer Center & RISE@CI-IPO, University of Porto, Porto, Portugal
- Gastroenterology Department, Portuguese Institute of Oncology of Porto, Porto, Portugal
| | - Hashem El-Serag
- Gastroenterology and Hepatology, Baylor College of Medicine, Houston, Texas, USA
- Houston VA Health Services Research & Development Center of Excellence, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - David Y Graham
- Department of Medicine, Michael E DeBakey Veterans Affairs Medical Center, Houston, Texas, USA
| | - Ernst J Kuipers
- Erasmus University Medical Center, Rotterdam, The Netherlands
| | | | - Jin Young Park
- International Agency for Research on Cancer, Lyon, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
| | | | - Emad M El-Omar
- Microbiome Research Centre, University of New South Wales, Sydney, New South Wales, Australia
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15
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Raoul P, Maccauro V, Cintoni M, Scarpellini E, Ianiro G, Gasbarrini A, Mele MC, Rinninella E. Microbiota-Gastric Cancer Interactions and the Potential Influence of Nutritional Therapies. Int J Mol Sci 2024; 25:1679. [PMID: 38338956 PMCID: PMC10855965 DOI: 10.3390/ijms25031679] [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: 12/25/2023] [Revised: 01/16/2024] [Accepted: 01/23/2024] [Indexed: 02/12/2024] Open
Abstract
Gastric cancer (GC) is one of the most common causes of cancer deaths, and GC treatments represent a large area of research. Although initially regarded as a sterile organ and unsuitable for microbial communities, the discovery of Helicobacter pylori made us realize that some microbes can colonize the stomach. In recent years, growing interest in gastric bacteria has expanded to the gut microbiota and, more recently, to the oral microbiota. Indeed, the oral-gastric-gut microbiota axis may play a crucial role in maintaining homeostasis, while changes in microbiota composition in GC patients can influence clinical outcomes. On the one hand, the microbiota and its metabolites may significantly influence the progression of GC, while anti-GC treatments such as gastrectomy and chemotherapy may significantly impact the oral-gastric-gut microbiota axis of GC patients. In this context, the role of nutritional therapies, including diet, prebiotics, and probiotics, in treating GC should not be underestimated. Wit this review, we aim to highlight the main role of the gastric, oral, and gut microbiota in GC onset and progression, representing potential future biomarkers for early GC detection and a target for efficient nutritional therapies during the course of GC.
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Affiliation(s)
- Pauline Raoul
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.M.)
| | - Valeria Maccauro
- School of Specialization in Internal Medicine, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Marco Cintoni
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
| | - Emidio Scarpellini
- Translationeel Onderzoek van Gastro-Enterologische Aandoeningen (T.A.R.G.I.D.), Gasthuisberg University 11 Hospital, KU Leuven, Herestraat 49, 3000 Leuven, Belgium;
| | - Gianluca Ianiro
- Digestive Disease Center (CEMAD), Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Digestive Disease Center (CEMAD), Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Maria Cristina Mele
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
| | - Emanuele Rinninella
- Clinical Nutrition Unit, Department of Medical and Abdominal Surgery and Endocrine-Metabolic Sciences, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy; (P.R.); (M.C.); (M.C.M.)
- Research and Training Center in Human Nutrition, Catholic University of the Sacred Heart, 00168 Rome, Italy;
- Department of Translational Medicine and Surgery, Catholic University of the Sacred Heart, 00168 Rome, Italy
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16
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Xu L, Liu X, Wu Q, Hua ZL, Yang F, Zhang JF. Phylogenetic analysis of pathogenic genes in Helicobacter species. Shijie Huaren Xiaohua Zazhi 2024; 32:58-70. [DOI: 10.11569/wcjd.v32.i1.58] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 12/01/2023] [Accepted: 01/11/2024] [Indexed: 01/26/2024] Open
Abstract
BACKGROUND Helicobacter bacteria are associated with gastrointestinal diseases, especially Helicobacter pylori (H. pylori). With the isolation of many non-Helicobacter pylori Helicobacters (NHPH) from the liver, intestines, and gallbladder of natural animal reservoirs, NHPH have been potential zoonotic pathogens, but their infection and pathogenic mechanisms are still unclear.
AIM To explore the phylogenetic relationship of Helicobacter species based on their pathogenic genes.
METHODS The present study collected the genomic sequences of 50 strains in genus Helicobacter, including 12 strains of H. pylori and 38 strains of NHPH. Based on 16S rRNA gene and several pathogenic genes (flagella, urease, and virulence factors), MAGA software (Version 11.0) was used to align their sequences and construct phylogenetic trees.
RESULTS The phylogenetic tree of 16S rRNA gene showed that gastric Helicobacter (GH) and enterohepatic Helicobacter species (EHS) were clustered into two large branches, respectively. All of the GH's hosts were mammals, while the hosts of EHS were many wild poultry and mammals. Based on the flagella motility-related genes (flaA, flaB, fliP, fliQ, fliR, fliG, fliM, and fliN), the phylogenetic trees were divided into two major branches (GH and EHS). Similarly, the phylogenetic trees of lipopolysaccharide (LPS) biosynthesis-related genes (lptA, waaC, and waaF) presented two major branches (GH and EHS), too. The urease genes existed in all of the 12 strains of H. pylori, 13 strains of gastric NHPH, and 4 strains of EHS (H. hepaticus, H. muridarum, H. bilis, and H. anseris). However, no significant phylogenetic patterns of GH and EHS were observed in the seven urease genes (ureA, ureB, ureE, ureF, ureG, ureH, and ureI).
CONCLUSION The phylogenetic relationship of Helicobacter species' pathogenic genes is dominated distinctly by the special colonization areas including gastric and enterohepatic niches.
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Affiliation(s)
- Le Xu
- School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
| | - Xing Liu
- School of Life Sciences, Nanjing Normal University, Nanjing 210023, Jiangsu Province, China
| | - Qi Wu
- Institute of Microbiology, Chinese Academy of Sciences, Beijing 100101, China
| | - Zhao-Lai Hua
- Institute of Tumor Prevention and Control, People's Hospital of Yangzhong City, Zhenjiang 212299, Jiangsu Province, China
| | - Fei Yang
- School of Life Sciences, Nanjing Normal University, Nanjing 210023, Jiangsu Province, China
| | - Jun-Feng Zhang
- School of Medicine, Nanjing University of Chinese Medicine, Nanjing 210023, Jiangsu Province, China
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Zhang S, Shen Y, Liu H, Zhu D, Fang J, Pan H, Liu W. Inflammatory microenvironment in gastric premalignant lesions: implication and application. Front Immunol 2023; 14:1297101. [PMID: 38035066 PMCID: PMC10684945 DOI: 10.3389/fimmu.2023.1297101] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/19/2023] [Accepted: 10/26/2023] [Indexed: 12/02/2023] Open
Abstract
Gastric precancerous lesions (GPL) are a major health concern worldwide due to their potential to progress to gastric cancer (GC). Understanding the mechanism underlying the transformation from GPL to GC can provide a fresh insight for the early detection of GC. Although chronic inflammation is prevalent in the GPL, how the inflammatory microenvironment monitored the progression of GPL-to-GC are still elusive. Inflammation has been recognized as a key player in the progression of GPL. This review aims to provide an overview of the inflammatory microenvironment in GPL and its implications for disease progression and potential therapeutic applications. We discuss the involvement of inflammation in the progression of GPL, highlighting Helicobacter pylori (H. pylori) as a mediator for inflammatory microenvironment and a key driver to GC progression. We explore the role of immune cells in mediating the progression of GPL, and focus on the regulation of inflammatory molecules in this disease. Furthermore, we discuss the potential of targeting inflammatory pathways for GPL. There are currently no specific drugs for GPL treatment, but traditional Chinese Medicine (TCM) and natural antioxidants, known as antioxidant and anti-inflammatory properties, exhibit promising effects in suppressing or reversing the progression of GPL. Finally, the challenges and future perspectives in the field are proposed. Overall, this review highlights the central role of the inflammatory microenvironment in the progression of GPL, paving the way for innovative therapeutic approaches in the future.
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Affiliation(s)
- Shengxiong Zhang
- Rehabilitation Department, Guangdong Work Injury Rehabilitation Hospital, Guangzhou, China
- Department of Spleen and Stomach, GuangZhou Tianhe District Hospital of Chinese Medicine, Guangzhou, China
- The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Yang Shen
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Hao Liu
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Di Zhu
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Jiansong Fang
- Science and Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Huafeng Pan
- Science and Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China
| | - Wei Liu
- The First Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou, China
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18
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Yu QY, Zhang HC, Jin H. Prediction of canceration of gastric ulcer with serum pepsinogen Ⅰ/Ⅱ ratio and gastrin-17. Shijie Huaren Xiaohua Zazhi 2023; 31:846-851. [DOI: 10.11569/wcjd.v31.i20.846] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2023] [Revised: 10/09/2023] [Accepted: 10/23/2023] [Indexed: 10/27/2023] Open
Abstract
BACKGROUND Screening sensitivity markers for canceration of gastric ulcer is of great significance for the prevention and treatment of gastric cancer. Previous studies have suggested that pepsinogen and gastrin-17 (G-17) may have appreciated value in the prediction of early gastric cancer, but there is still no definitive consensus on this.
AIM To assess the clinical value of serum pepsinogen I (PGⅠ)/pepsinogen Ⅱ (PGⅡ) ratio combined with G-17 in predicting canceration of gastric ulcer to provide sensitive biochemical markers for early diagnosis of gastric cancer.
METHODS A retrospective analysis was conducted on 215 patients with gastric ulcer at our hospital from July 2020 to April 2023. According to the histopathological diagnosis by gastroscopy, the patients were divided into either a simple ulcer group (184 cases) or a gastric cancer group (31 cases). Serum PGⅠ, PGⅡ, G-17, and tumor markers [including carbohydrate antigen (CA)724, CA199, carcinoembryonic antigen (CEA), and ferritin] were detected on admission. The delta over baseline (DOB) value of Helicobacter pylori (H. pylori) infection was measured by the 13C breath test.
RESULTS There were no differences in gender, age, DOB value, or disease course between the two groups (P > 0.05). Compared with the simple ulcer group, serum levels of PGⅡ, G-17, CA724, CA199, and CEA in the gastric cancer group were increased, while PGⅠ, ferritin, and PGⅠ/PGⅡ ratio were decreased (P < 0.05). Spearman test showed that PGⅠ/PGⅡ ratio was negatively correlated with G-17, CA724, CA199, and CEA, and positively correlated with ferritin (P < 0.05). G-17 was positively correlated with CA724, CA199, and CEA, and negatively correlated with ferritin (P < 0.05). Receiver operating curve (ROC) analysis showed that the area under the ROC curve (AUC) of PGⅠ/PGⅡ ratio and G-17 for diagnosing canceration of gastric ulcer was 0.804 and 0.742, respectively. The AUC of PGⅠ/PGⅡ ratio combined with G-17 was 0.899, significantly higher than that of either indicator alone (P < 0.05).
CONCLUSION The decrease of serum PGⅠ/PGⅡ ratio and increase of G-17 are closely related to the canceration of gastric ulcer. The combination of PGⅠ/PGⅡ ratio and G-17 has good predictive performance for canceration of gastric ulcer. PGⅠ/PGⅡ ratio and G-17 can serve as sensitive biomarkers for the early diagnosis of gastric cancer.
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Affiliation(s)
- Qiao-Yan Yu
- Department of Gastroenterology, Jinhua Guangfu Cancer Hospital, Jinhua 321000, Zhejiang Province, China
| | - Hong-Cheng Zhang
- Department of Gastroenterology, Jinhua Guangfu Cancer Hospital, Jinhua 321000, Zhejiang Province, China
| | - Hao Jin
- Department of Gastroenterology, Jinhua Guangfu Cancer Hospital, Jinhua 321000, Zhejiang Province, China
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19
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Komori E, Kato-Kogoe N, Imai Y, Sakaguchi S, Taniguchi K, Omori M, Ohmichi M, Nakamura S, Nakano T, Lee SW, Ueno T. Changes in salivary microbiota due to gastric cancer resection and its relation to gastric fluid microbiota. Sci Rep 2023; 13:15863. [PMID: 37740058 PMCID: PMC10516953 DOI: 10.1038/s41598-023-43108-8] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2023] [Accepted: 09/20/2023] [Indexed: 09/24/2023] Open
Abstract
Gastric cancer is one of the leading causes of death worldwide, and resections are performed to cure the disease. We have previously reported the changes in the gastric microbiota after gastric cancer resection, which may be associated with the oral microbiota; however, the changes in the oral microbiota remain uncharacterized. This study aimed to characterize the changes in the salivary microbiota caused by gastric cancer resection and to evaluate their association with the gastric fluid microbiota. Saliva and gastric fluid samples were collected from 63 patients who underwent gastrectomy before and after surgery, and a 16S rRNA metagenomic analysis was performed to compare the microbiota composition. The number of bacterial species in the salivary microbiota decreased, and the bacterial composition changed after the resection of gastric cancer. In addition, we identified several bacterial genera that varied significantly in the salivary microbiota, some of which also showed similar changes in the gastric fluid microbiota. These findings indicate that changes in the gastric environment affect the oral microbiota, emphasizing the close association between the oral and gastric fluid microbiota. Our study signifies the importance of focusing on the oral microbiota in the perioperative period of gastrectomy in patients with gastric cancer.
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Affiliation(s)
- Eri Komori
- Department of Dentistry and Oral Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Nahoko Kato-Kogoe
- Department of Dentistry and Oral Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan.
| | - Yoshiro Imai
- Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Shoichi Sakaguchi
- Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Kohei Taniguchi
- Translational Research Program, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Michi Omori
- Department of Dentistry and Oral Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Mayu Ohmichi
- Department of Dentistry and Oral Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Shota Nakamura
- Department of Infection Metagenomics, Genome Information Research Center, Research Institute for Microbial Diseases, Osaka University, Suita, Japan
| | - Takashi Nakano
- Department of Microbiology and Infection Control, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Sang-Woong Lee
- Department of General and Gastroenterological Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
| | - Takaaki Ueno
- Department of Dentistry and Oral Surgery, Faculty of Medicine, Osaka Medical and Pharmaceutical University, 2-7 Daigaku-machi, Takatsuki City, Osaka, 569-8686, Japan
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20
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Dadgar N, Edlukudige Keshava V, Raj MS, Wagner PL. The Influence of the Microbiome on Immunotherapy for Gastroesophageal Cancer. Cancers (Basel) 2023; 15:4426. [PMID: 37760397 PMCID: PMC10526145 DOI: 10.3390/cancers15184426] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2023] [Revised: 08/27/2023] [Accepted: 08/30/2023] [Indexed: 09/29/2023] Open
Abstract
Immunotherapy has shown promise as a treatment option for gastroesophageal cancer, but its effectiveness is limited in many patients due to the immunosuppressive tumor microenvironment (TME) commonly found in gastrointestinal tumors. This paper explores the impact of the microbiome on the TME and immunotherapy outcomes in gastroesophageal cancer. The microbiome, comprising microorganisms within the gastrointestinal tract, as well as within malignant tissue, plays a crucial role in modulating immune responses and tumor development. Dysbiosis and reduced microbial diversity are associated with poor response rates and treatment resistance, while specific microbial profiles correlate with improved outcomes. Understanding the complex interactions between the microbiome, tumor biology, and immunotherapy is crucial for developing targeted interventions. Microbiome-based biomarkers may enable personalized treatment approaches and prediction of patient response. Interventions targeting the microbiome, such as microbiota-based therapeutics and dietary modifications, offer the potential for reshaping the gut microbiota and creating a favorable TME that enhances immunotherapy efficacy. Further research is needed to reveal the underlying mechanisms, and large-scale clinical trials will be required to validate the efficacy of microbiome-targeted interventions.
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Affiliation(s)
- Neda Dadgar
- Cole Eye Institute, Cleveland Clinic, Cleveland, OH 44106, USA;
| | | | - Moses S. Raj
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.E.K.); (M.S.R.)
| | - Patrick L. Wagner
- Allegheny Health Network Cancer Institute, Pittsburgh, PA 15224, USA; (V.E.K.); (M.S.R.)
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21
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Nishino M, Kakiuchi T, Fukuda K, Yoshiura M. Case report: A pediatric case of repeated false-positive urea breath test for Helicobacter pylori without decreased gastric acid secretion. Front Med (Lausanne) 2023; 10:1267180. [PMID: 37724177 PMCID: PMC10505434 DOI: 10.3389/fmed.2023.1267180] [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: 07/26/2023] [Accepted: 08/23/2023] [Indexed: 09/20/2023] Open
Abstract
The urea breath test (UBT) is often used to diagnose Helicobacter pylori infection and for its eradication. However, this text can give positive results even for other urease-active bacteria other than H. pylori. Even after the successful eradication of H. pylori, the presence of other urease-active bacteria in the gut and oral cavity can lead to positive UBT results in patients with decreased gastric acid secretion. Herein, a 15-year-old boy was diagnosed with H. pylori infection through the testing and treatment program for H. pylori for third-year junior high-school students in Saga Prefecture initiated in 2016. He underwent triple therapy comprising vonoprazan; however, UBT was found to be positive even after therapy. The results remained positive even after fourth-line eradication therapy. Stool antigen, PCR using gastric fluid, microscopy, culture, and rapid urease tests were all negative. Pepsinogen levels were normal, and none of the findings suggested autoimmune gastritis. Gastric microflora analysis revealed oral flora showing urease activity. UBT is considered useful for determining the successful eradication of H. pylori; however, it may give false-positive results for both H. pylori infection and eradication judgment. Although the patient did not have autoimmune gastritis or decreased gastric acid secretion, it is presumed that oral commensal bacteria showing urease activity inhabited the stomach, resulting in the persistently positive UBT results. In conclusion, repeated false-positive UBT results for H. pylori may occur even without gastric acid hyposecretion. If H. pylori eradication is unsuccessful based on UBT, additional test by stool H. pylori antigen tests should be considered.
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Affiliation(s)
- Masafumi Nishino
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Toshihiko Kakiuchi
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
| | - Kayoko Fukuda
- Department of Gastroenterology, Hiramatsu Hospital, Ogi, Saga, Japan
| | - Masato Yoshiura
- Department of Pediatrics, Faculty of Medicine, Saga University, Saga, Japan
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22
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Hua Z, Xu L, Zhu J, Xiao L, Lu B, Wu J, Wu Z, Zhou Q, Zhang J. Helicobacter pylori infection altered gastric microbiota in patients with chronic gastritis. Front Cell Infect Microbiol 2023; 13:1221433. [PMID: 37662018 PMCID: PMC10470091 DOI: 10.3389/fcimb.2023.1221433] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Objective The present study aims to investigate the effect of Helicobacter pylori (Hp) infection on gastric mucosal microbiota in patients with chronic gastritis. Methods Here recruited a population of 193 patients with both chronic gastritis and positive rapid urease, including 124 patients with chronic atrophic gastritis (CAG) and 69 patients with chronic non-atrophic gastritis (nCAG). Immunoblotting was used to detect four serum Hp antibodies (UreA, UreB, VacA and CagA) to determine the types of virulent Hp-I and avirulent Hp-II infections. Gastric microbiota was profiled by 16S rRNA gene V3-V4 region, and R software was used to present the relationship between the microbial characteristics and the type of Hp infection. Results In the stomach of patients with Hp-positive gastritis, the dominant gastric bacterial genera included Ralstonia (23.94%), Helicobacter (20.28%), Pseudonocardia (9.99%), Mesorhizobium (9.21%), Bradyrhizobium (5.05%), and Labrys (4.75%). The proportion of Hp-I infection was significantly higher in CAG patients (91.1%) than in nCAG patients (71.0%) (P < 0.001). The gastric microbiota richness index (observed OTUs, Chao) was significantly lower in CAG patients than in nCAG patients (P <0.05). Compared with avirulent Hp-II infection, virulent Hp-I infection significantly decreased the Shannon index in CAG patients (P <0.05). In nCAG patients, Hp-I infected patients had lower abundances of several dominant gastric bacteria (Aliidiomarina, Reyranella, Halomonas, Pseudomonas, Acidovorax) than Hp-II infected patients. Meanwhile, in CAG patients, Hp-I infected patients occupied lower abundances of several dominant oral bacteria (Neisseria, Staphylococcus and Haemophilus) than Hp-II infected patients. In addition, bile reflux significantly promoted the colonization of dominant oral microbiota (Veillonella, Prevotella 7 and Rothia) in the stomach of CAG patients. There was no significant symbiotic relationship between Helicobacter bacteria and non-Helicobacter bacteria in the stomach of nCAG patients, while Helicobacter bacteria distinctly linked with the non-Helicobacter bacteria (Pseudolabrys, Ralstonia, Bradyrhizobium, Mesorhizobium and Variovorax) in CAG patients. Conclusions Virulent Hp infection alters the gastric microbiota, reduces microbial diversity, and enhances the symbiotic relationship between the Helicobacter bacteria and non-Helicobacter bacteria in patients with chronic gastritis. The data provides new evidence for treating Hp infection by improving the gastric microbiota.
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Affiliation(s)
- Zhaolai Hua
- Guangxi Key Laboratory of Rare and Endangered Animal Ecology, Guangxi Normal University, Guilin, China
- Institute of Tumor Prevention and Control, People’s Hospital of Yangzhong City, Yangzhong, China
| | - Le Xu
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Jiahui Zhu
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Ling Xiao
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Bin Lu
- Department of Oncology, People’s Hospital of Yangzhong City, Yangzhong, China
| | - Jianping Wu
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
| | - Zhenfeng Wu
- Department of Surgical Oncology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, China
| | - Qihai Zhou
- Guangxi Key Laboratory of Rare and Endangered Animal Ecology, Guangxi Normal University, Guilin, China
| | - Junfeng Zhang
- School of Medicine and Holistic Integrative Medicine, Nanjing University of Chinese Medicine, Nanjing, China
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23
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Jiang C, Zhang J, Wang W, Shan Z, Sun F, Tan Y, Tong Y, Qiu Y. Extracellular vesicles in gastric cancer: role of exosomal lncRNA and microRNA as diagnostic and therapeutic targets. Front Physiol 2023; 14:1158839. [PMID: 37664422 PMCID: PMC10469264 DOI: 10.3389/fphys.2023.1158839] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Accepted: 07/31/2023] [Indexed: 09/05/2023] Open
Abstract
Extracellular vesicles (EVs), including exosomes, play a crucial role in intercellular communication and have emerged as important mediators in the development and progression of gastric cancer. This review discusses the current understanding of the role of EVs, particularly exosomal lncRNA and microRNA, in gastric cancer and their potential as diagnostic and therapeutic targets. Exosomes are small membrane-bound particles secreted by both cancer cells and stromal cells within the tumor microenvironment. They contain various ncRNA and biomolecules, which can be transferred to recipient cells to promote tumor growth and metastasis. In this review, we highlighted the importance of exosomal lncRNA and microRNA in gastric cancer. Exosomal lncRNAs have been shown to regulate gene expression by interacting with transcription factors or chromatin-modifying enzymes, which regulate gene expression by binding to target mRNAs. We also discuss the potential use of exosomal lncRNAs and microRNAs as diagnostic biomarkers for gastric cancer. Exosomes can be isolated from various bodily fluids, including blood, urine, and saliva. They contain specific molecules that reflect the molecular characteristics of the tumor, making them promising candidates for non-invasive diagnostic tests. Finally, the potential of targeting exosomal lncRNAs and microRNAs as a therapeutic strategy for gastric cancer were reviewed as wee. Inhibition of specific molecules within exosomes has been shown to suppress tumor growth and metastasis in preclinical models. In conclusion, this review article provides an overview of the current understanding of the role of exosomal lncRNA and microRNA in gastric cancer. We suggest that further research into these molecules could lead to new diagnostic tools and therapeutic strategies for this deadly disease.
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Affiliation(s)
- Chengyao Jiang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Jianjun Zhang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Wentao Wang
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Zexing Shan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Fan Sun
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yuen Tan
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yilin Tong
- Department of Gastric Surgery, Liaoning Cancer Hospital and Institute, Cancer Hospital of China Medical University, Shenyang, China
| | - Yue Qiu
- Medical Oncology Department of Gastrointestinal Cancer, Cancer Hospital of China Medical University, Liaoning Cancer Hospital and Institute, Shenyang, Liaoning, China
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24
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Miri AH, Kamankesh M, Rad-Malekshahi M, Yadegar A, Banar M, Hamblin MR, Haririan I, Aghdaei HA, Zali MR. Factors associated with treatment failure, and possible applications of probiotic bacteria in the arsenal against Helicobacter pylori. Expert Rev Anti Infect Ther 2023; 21:617-639. [PMID: 37171213 DOI: 10.1080/14787210.2023.2203382] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/13/2023]
Abstract
INTRODUCTION Helicobacter pylori is a widespread helical Gram-negative bacterium, which causes a variety of stomach disorders, such as peptic ulcer, chronic atrophic gastritis, and gastric cancer. This microbe frequently colonizes the mucosal layer of the human stomach and survives in the inhospitable microenvironment, by adapting to this hostile milieu. AREAS COVERED In this extensive review, we describe conventional antibiotic treatment regimens used against H. pylori including, empirical, tailored, and salvage therapies. Then, we present state-of-the-art information about reasons for treatment failure against H. pylori. Afterward, the latest advances in the use of probiotic bacteria against H. pylori infection are discussed. Finally, we propose a polymeric bio-platform to provide efficient delivery of probiotics for H. pylori infection. EXPERT OPINION For effective probiotic delivery systems, it is necessary to avoid the early release of probiotics at the acidic stomach pH, to protect them against enzymes and antimicrobials, and precisely target H. pylori bacteria which have colonized the antrum area of the stomach (basic pH).
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Affiliation(s)
- Amir Hossein Miri
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mojtaba Kamankesh
- Polymer Chemistry Department, School of Science, University of Tehran, Tehran, Iran
| | - Mazda Rad-Malekshahi
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran 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
| | - Maryam Banar
- Department of Pathobiology, School of Public Health, Tehran University of Medical Sciences, Tehran, Iran
| | - Michael R Hamblin
- Laser Research Centre, Faculty of Health Science, University of Johannesburg Doornfontein, Johannesburg, South Africa
| | - Ismaeil Haririan
- Department of Pharmaceutical Biomaterials and Medical Biomaterials Research Center, Faculty of Pharmacy, Tehran 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
| | - 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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25
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Yu T, Lu T, Deng W, Yao D, He C, Luo P, Song J. Microbiome and function alterations in the gastric mucosa of asymptomatic patients with Helicobacter pylori infection. Helicobacter 2023; 28:e12965. [PMID: 36890119 DOI: 10.1111/hel.12965] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Revised: 02/22/2023] [Accepted: 02/23/2023] [Indexed: 03/10/2023]
Abstract
BACKGROUND Most patients with Helicobacter pylori (H. pylori) infection have no clinical symptoms, numerous studies reported the gastric microbiome in H. pylori-infected patients, but asymptomatic patients have not been distinguished. How the microbiome and function changes in asymptomatic patients with H. pylori infection remains poorly understood. METHODS A total of 29 patients were divided into H. pylori-infected asymptomatic group (10 patients), H. pylori-infected symptomatic group (11 patients) and H. pylori-uninfected group (8 patients). Gastric mucosa specimens were taken for histopathological examination, special staining, and 16 S rDNA sequencing. High-throughput results were evaluated by community composition analysis, indicator species analysis, alpha diversity analysis, beta diversity analysis, and function prediction. RESULTS The gastric microbiota composition at phylum and genus level of H. pylori-infected asymptomatic patients were similar with H. pylori-infected symptomatic group, but different from H. pylori-uninfected patients. The diversity and richness of gastric microbial community declined significantly in H. pylori-infected asymptomatic group comparing with H. pylori-uninfected group. Sphingomonas may be an indicator between symptomatic and asymptomatic patients with H. pylori infection, the AUC value of Sphingomonas is 0.79. Interactions between species increased and altered notably after H. pylori infection. More genera were affected by Helicobacter in H. pylori-infected asymptomatic patients. The function condition changed significantly in asymptomatic patients with H. pylori infection, there was no difference comparing with symptomatic ones. Amino acid metabolism and lipid metabolism strengthened but carbohydrate metabolism remained constant after H. pylori infection. The metabolism of fatty acid and bile acid was disturbed after infection with H. pylori. CONCLUSION The gastric microbiota composition and function mode changed significantly after H. pylori infection regardless of the presence of clinical symptoms, there was no difference between H. pylori-infected asymptomatic and symptomatic patients. The difference in gastric microbiota composition and interactions between species might be responsible for presence of digestive symptoms.
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Affiliation(s)
- Tingting Yu
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Tianyu Lu
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Wei Deng
- Department of Pathology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Danping Yao
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Cheng He
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Peng Luo
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
| | - Jian Song
- Department of Gastroenterology, Southern University of Science and Technology Hospital, Shenzhen, China
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26
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Mannion A, Sheh A, Shen Z, Dzink-Fox J, Piazuelo MB, Wilson KT, Peek R, Fox JG. Shotgun Metagenomics of Gastric Biopsies Reveals Compositional and Functional Microbiome Shifts in High- and Low-Gastric-Cancer-Risk Populations from Colombia, South America. Gut Microbes 2023; 15:2186677. [PMID: 36907988 PMCID: PMC10026914 DOI: 10.1080/19490976.2023.2186677] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2022] [Accepted: 02/27/2023] [Indexed: 03/14/2023] Open
Abstract
Along with Helicobacter pylori infection, the gastric microbiota is hypothesized to modulate stomach cancer risk in susceptible individuals. Whole metagenomic shotgun sequencing (WMS) is a sequencing approach to characterize the microbiome with advantages over traditional culture and 16S rRNA sequencing including identification of bacterial and non-bacterial taxa, species/strain resolution, and functional characterization of the microbiota. In this study, we used WMS to survey the microbiome in extracted DNA from antral gastric biopsy samples from Colombian patients residing in the high-risk gastric cancer town Túquerres (n = 10, H. pylori-positive = 7) and low-risk town of Tumaco (n = 10, H. pylori-positive = 6). Kraken2/Bracken was used for taxonomic classification and abundance. Functional gene profiles were inferred by InterProScan and KEGG analysis of assembled contigs and gene annotation. The most abundant taxa represented bacteria, non-human eukaryota, and viral genera found in skin, oral, food, and plant/soil environments including Staphylococus, Streptococcus, Bacillus, Aspergillus, and Siphoviridae. H. pylori was the predominant taxa present in H. pylori-positive samples. Beta diversity was significantly different based on H. pylori-status, risk group, and sex. WMS detected more bacterial taxa than 16S rRNA sequencing and aerobic, anaerobic, and microaerobic culture performed on the same gastric biopsy samples. WMS identified significant differences in functional profiles found between H. pylori-status, but not risk or sex groups. H. pylori-positive samples were significantly enriched for H. pylori-specific genes including virulence factors such as vacA, cagA, and urease, while carbohydrate and amino acid metabolism genes were enriched in H. pylori-negative samples. This study shows WMS has the potential to characterize the taxonomy and function of the gastric microbiome as risk factors for H. pylori-associated gastric disease. Future studies will be needed to compare and validate WMS versus traditional culture and 16S rRNA sequencing approaches for characterization of the gastric microbiome.
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Affiliation(s)
- Anthony Mannion
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Alexander Sheh
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - Zeli Shen
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - JoAnn Dzink-Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
| | - M. Blanca Piazuelo
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Keith T Wilson
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - Richard Peek
- Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA
| | - James G. Fox
- Division of Comparative Medicine, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
- Department of Biological Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts, USA
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27
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Wang YZ, Chen J, Pei SQ, Wang C, Han G, Kan LD, Li LC. Treatment strategies and pharmacist-led medication management for Helicobacter pylori infection. Drug Dev Res 2022; 84:326-336. [PMID: 36567647 DOI: 10.1002/ddr.22025] [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: 07/30/2022] [Revised: 12/05/2022] [Accepted: 12/11/2022] [Indexed: 12/27/2022]
Abstract
Half of the world's population is Helicobacter pylori carrier. Updated guidelines and consensus have been issued across regions with the main aim of reducing social transmission and increasing H. pylori eradication rate. Although alternative therapies including traditional Chinese medicine and probiotics have also been used to improve H. pylori eradication rate in clinical practice, current mainstream treatment is still dependent on triple and quadruple therapies that includes antibacterial agents (e.g., amoxicillin and furazolidone) and proton pump inhibitor. Researches also assessed the eradication rate of optimized high-dose dual therapy in treating H. pylori infection. With the increase of antibiotic resistance rate, the treatment strategies for H. pylori infection are constantly adjusted and improved. Besides, low medication compliance is another key influencing factor for H. pylori treatment failure. Emerging studies indicate that pharmacists' intervention and new pharmaceutical care methods can enhance patient medication compliance, reduce adverse drug reactions, and improve H. pylori eradication rate. The purpose of this review is to summarize the advances in treating H. pylori infection and highlight the necessity of developing novel strategies to cope with the increasing challenges and to achieve personalized medication. Also, this review attaches great importance to pharmacists in optimizing H. pylori treatment outcomes as a routine part of therapy.
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Affiliation(s)
- Yu-Zhen Wang
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Jie Chen
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Shi-Qin Pei
- School of Pharmacy, Hangzhou Medical College, Hangzhou, China
| | - Chen Wang
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Gang Han
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Lian-Di Kan
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
| | - Liu-Cheng Li
- Department of Pharmacy, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China
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