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He X, Chen H, Chen F, Su W, Wang Y, Hu D, Hu J, Zhou X. Characterization of Fecal Microbial Communities in Patients With Type 2 Diabetes Mellitus Combined With Helicobacter pylori Infection. Helicobacter 2025; 30:e70041. [PMID: 40338991 DOI: 10.1111/hel.70041] [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: 12/07/2024] [Revised: 04/17/2025] [Accepted: 04/23/2025] [Indexed: 05/10/2025]
Abstract
BACKGROUND Helicobacter pylori (H. pylori) infection has the capacity to alter the gut microbiota composition. There is a significant correlation between H. pylori infection and type 2 diabetes mellitus (T2DM). Further research is necessary to explore whether gut microbiota plays a role in the relationship between H. pylori and T2DM. METHOD Fecal samples were obtained from 44 patients with T2DM, including 20 who tested positive for H. pylori and 24 who tested negative. Intestinal microbiota composition was analyzed via 16S rRNA V3-V4 amplicon sequencing. Differences in microbial distribution and significant microbial biomarkers were identified between H. pylori positive and negative groups. A Spearman correlation analysis assessed the relationship between intestinal microbiota and glycemic parameters. Additionally, PICRUSt2 was used to predict intestinal bacterial functions. RESULTS Results indicate that in H. pylori (+) T2DM patients, HbA1c levels were significantly higher (8.9% vs. 8.1%, p = 0.021), while both the C-peptide peak (3.70 vs. 5.98 ng/mL, p = 0.040) and fasting C-peptide levels (1.42 vs. 2.31 ng/mL, p = 0.008) were significantly lower compared to H. pylori (-) T2DM groups. A total of 11 colonic phyla and 100 genera were identified in all fecal samples. In groups positive for H. pylori, there was a significant enrichment of the phylum Proteobacteria, while the genera Lactobacillus, Butyricimonas, and Akkermansia were significantly reduced (all p < 0.05). Correlation analysis showed that the abundance of the genera Butyricimonas (p = 0.01) and Akkermansia (p = 0.048) were negatively correlated with fasting plasma glucose. KEGG pathway analysis indicated a significant enrichment of methylmalonyl-CoA mutase and succinyl-CoA in H. pylori-infected T2DM patients. CONCLUSIONS This study suggests that T2DM patients with H. pylori infection exhibit more impaired pancreatic islet function potentially due to H. pylori-induced alterations in the gut microbiota.
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Affiliation(s)
- Xiaoyan He
- Department of Gastroenterology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Han Chen
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Fengdan Chen
- Department of Endocrinology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Wei Su
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Yan Wang
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Die Hu
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Jianwen Hu
- Department of Gastroenterology, Dongyang Hospital Affiliated to Wenzhou Medical University, Dongyang, China
| | - Xiaoying Zhou
- Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 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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3
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Liu Z, Xu H, You W, Pan K, Li W. Helicobacter pylori eradication for primary prevention of gastric cancer: progresses and challenges. JOURNAL OF THE NATIONAL CANCER CENTER 2024; 4:299-310. [PMID: 39735441 PMCID: PMC11674435 DOI: 10.1016/j.jncc.2024.06.006] [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: 04/26/2024] [Revised: 06/20/2024] [Accepted: 06/27/2024] [Indexed: 12/31/2024] Open
Abstract
Gastric cancer remains a significant global health challenge, causing a substantial number of cancer-related deaths, particularly in China. While the exact causes of gastric cancer are still being investigated, Helicobacter pylori (H. pylori) infection has been identified as the primary risk factor, which triggers chronic inflammation and a multistage progression of gastric lesions that may lead to carcinogenesis over a long latency time. Since the 1990s, numerous efforts have focused on assessing the effectiveness of H. pylori eradication in preventing new cases of gastric cancer among both the general population and patients who have undergone early-stage cancer treatment. This body of work, including several community-based interventions and meta-analyses, has shown a reduction in both the incidence of and mortality from gastric cancer following H. pylori treatment, alongside a decreased risk of metachronous gastric cancer. In this review, we seek to consolidate current knowledge on the effects of H. pylori treatment on gastric cancer prevention, its systemic consequences, cost-effectiveness, and the influence of antibiotic resistance and host characteristics on treatment outcomes. We further discuss the potential for precision primary prevention of H. pylori treatment and comment on the efficient implementation of test-and-treat policies and allocation of health resources towards minimizing the burden of gastric cancer globally.
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Affiliation(s)
- Zongchao Liu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Hengmin Xu
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Weicheng You
- Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Cancer Epidemiology, Peking University Cancer Hospital and Institute, Beijing, China
| | - Kaifeng Pan
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
| | - Wenqing Li
- State Key Laboratory of Holistic Integrative Management of Gastrointestinal Cancers, Beijing Key Laboratory of Carcinogenesis and Translational Research, Department of Cancer Epidemiology, Peking University Cancer Hospital & Institute, Beijing, China
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4
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Yan Y, Dong L, Xu J, Zhang Z, Jia P, Zhang J, Chen W, Gao W. Preliminary study on the potential impact of probiotic combination therapy on Helicobacter pylori infection in children using 16S gene sequencing and untargeted metabolomics approach. Front Microbiol 2024; 15:1487978. [PMID: 39545236 PMCID: PMC11560915 DOI: 10.3389/fmicb.2024.1487978] [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: 08/30/2024] [Accepted: 10/21/2024] [Indexed: 11/17/2024] Open
Abstract
Objective The purpose of this study was to explore the potential mechanism of Helicobacter pylori (Hp) eradication by probiotic therapy through 16S rRNA gene sequencing technology and untargeted metabolomics. Methods Twenty four Hp-infected children were recruited from the Shanxi Bethune Hospital, and 24 healthy children were recruited as a blank control group. Group A: fecal samples from 24 healthy children. Group B: fecal samples of 24 children with Hp infection. Group B1 (n = 15): fecal samples of group B treated with probiotic therapy for 2 weeks. Group B2 (n = 19): fecal samples of group B treated with probiotic therapy for 4 weeks. The above fecal samples were analyzed by 16S rRNA gene sequencing technology and untargeted metabolomics. Results There was no significant difference in alpha diversity and beta diversity among the four groups, but many bacteria with statistical difference were found in each group at the bacterial genus level and phylum level. LEfSe results showed that in group B, Porphyromonadaceae, Shigella and other microorganisms related to intestinal microecological dysbiosis were enriched. And in group B2, abundant characteristic microorganisms were found, namely Bacillales and Prevotella. KEGG metabolic pathway enrichment analysis showed that groups B1 and B2 were involved in 10 metabolic pathways potentially related to probiotic treatment: purine metabolism, nitrogen metabolism, arginine biosynthesis, alanine, aspartic acid and glutamate metabolism, glyoxylic acid and dicarboxylic acid metabolism, unsaturated fatty acid biosynthesis, fatty acid extension, fatty acid degradation, pyrimidine metabolism, fatty acid biosynthesis. Conclusion Probiotic therapy can inhibit Hp to some extent and can relieve gastrointestinal symptoms, making it a preferred therapy for children with Hp infection and functional abdominal pain. Hp infection can reduce the diversity of intestinal microbes, resulting in the disturbance of intestinal microbiota and changes in the relative abundance of microbiota in children, while probiotic therapy can restore the diversity of intestinal microbes and intestinal microecological balance.
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Affiliation(s)
- Ya Yan
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Lingjun Dong
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Juan Xu
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Zhijiao Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Pengyan Jia
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Jingmin Zhang
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
| | - Weihong Chen
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
| | - Weiqi Gao
- Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China
- School of Pharmacy, Shanxi Medical University, Taiyuan, China
- Shanxi Academy of Advanced Research and Innovation (SAARI), Taiyuan, China
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Yao M, Cao J, Zhang L, Wang K, Lin H, Qin L, Zhang Q, Qu C, Miao J, Xue C. Indole-3-Lactic Acid Derived from Lacticaseibacillus paracasei Inhibits Helicobacter pylori Infection via Destruction of Bacteria Cells, Protection of Gastric Mucosa Epithelial Cells, and Alleviation of Inflammation. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2024; 72:15725-15739. [PMID: 38973111 DOI: 10.1021/acs.jafc.4c02868] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 07/09/2024]
Abstract
Indole-3-lactic acid (ILA) has exhibited antimicrobial properties. However, its role in inhibiting Helicobacter pylori infection remains elusive. This study investigated the inhibitory effect of ILA produced by Lacticaseibacillus paracasei on H. pylori, which was further confirmed by cell and animal experiments. 5 mg/mL ILA was sufficient to directly inhibit the growth of H. pylori in vitro, with a urease inhibitory activity reaching 60.94 ± 1.03%, and the cell morphology and structure were destroyed. ILA inhibited 56.5% adhesion of H. pylori to GES-1 and significantly reduced the number of apoptotic cells. Furthermore, ILA suppresses H. pylori colonization by approximately 38% to 63%, reduced inflammation and oxidative stress in H. pylori-infected mice, and enhanced the enrichment and variety of gut microbiota, notably fostering the growth of beneficial bacteria such as Lactobacillus and Bifidobacterium strains. The results support that ILA derived from Lactobacillus can be applicated as a novel prebiotic in anti-H. pylori functional foods.
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Affiliation(s)
- Mengke Yao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Junhan Cao
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Liping Zhang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Kai Wang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Huan Lin
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Ling Qin
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Qing Zhang
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
| | - Changfeng Qu
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China
- Marine Natural Products R&D Laboratory, Qingdao Key Laboratory, Qingdao 266061, China
| | - Jinlai Miao
- Key Laboratory of Marine Eco-Environmental Science and Technology, First Institute of Oceanography, Ministry of Natural Resources, Qingdao 266061, China
- Laboratory for Marine Drugs and Bioproducts, Qingdao Pilot National Laboratory for Marine Science and Technology, Qingdao 266237, China
- Marine Natural Products R&D Laboratory, Qingdao Key Laboratory, Qingdao 266061, China
| | - Changhu Xue
- College of Food Science and Engineering, Ocean University of China, Qingdao 266003, China
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6
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Senthil Kumar S, Johnson MDL, Wilson JE. Insights into the enigma of oral streptococci in carcinogenesis. Microbiol Mol Biol Rev 2024; 88:e0009523. [PMID: 38506551 PMCID: PMC11338076 DOI: 10.1128/mmbr.00095-23] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 03/21/2024] Open
Abstract
SUMMARYThe genus Streptococcus consists of a taxonomically diverse group of Gram-positive bacteria that have earned significant scientific interest due to their physiological and pathogenic characteristics. Within the genus Streptococcus, viridans group streptococci (VGS) play a significant role in the oral ecosystem, constituting approximately 80% of the oral biofilm. Their primary role as pioneering colonizers in the oral cavity with multifaceted interactions like adherence, metabolic signaling, and quorum sensing contributes significantly to the complex dynamics of the oral biofilm, thus shaping oral health and disease outcomes. Perturbations in oral streptococci composition drive oral dysbiosis and therefore impact host-pathogen interactions, resulting in oral inflammation and representing VGS as an opportunistic pathogen. The association of oral streptococci in tumors across distant organs, spanning the esophagus, stomach, pancreas, and colon, illuminates a potential association between oral streptococci, inflammation, and tumorigenesis. This finding emphasizes the need for further investigations into the role of oral streptococci in mucosal homeostasis and their involvement in carcinogenesis. Hence, here, we review the significance of oral streptococci in biofilm dynamics and how the perturbation may impact mucosal immunopathogenesis in the context of cancer, with a vision of exploiting oral streptococci for cancer intervention and for the development of non-invasive cancer diagnosis.
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Affiliation(s)
- Sangeetha Senthil Kumar
- Department of
Immunobiology, The University of
Arizona, Tucson,
Arizona, USA
- The University of
Arizona Cancer Center,
Tucson, Arizona, USA
| | - Michael D. L. Johnson
- Department of
Immunobiology, The University of
Arizona, Tucson,
Arizona, USA
- Valley Fever Center
for Excellence, The University of Arizona College of
Medicine, Tucson,
Arizona, USA
- BIO5 Institute, The
University of Arizona College of
Medicine, Tucson,
Arizona, USA
- Asthma and Airway
Disease Research Center, The University of Arizona College of
Medicine, Tucson,
Arizona, USA
| | - Justin E. Wilson
- Department of
Immunobiology, The University of
Arizona, Tucson,
Arizona, USA
- The University of
Arizona Cancer Center,
Tucson, Arizona, USA
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7
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Tohumcu E, Kaitsas F, Bricca L, Ruggeri A, Gasbarrini A, Cammarota G, Ianiro G. Helicobacter pylori and the Human Gastrointestinal Microbiota: A Multifaceted Relationship. Antibiotics (Basel) 2024; 13:584. [PMID: 39061266 PMCID: PMC11274338 DOI: 10.3390/antibiotics13070584] [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: 05/17/2024] [Revised: 06/17/2024] [Accepted: 06/20/2024] [Indexed: 07/28/2024] Open
Abstract
Helicobacter pylori is a type of Gram-negative bacteria belonging to the Proteobacteria phylum which is known to cause gastrointestinal disorders such as gastritis and gastric ulcers. Its treatment is based on current eradication regimens, which are composed of combinations of antibiotics such as clarithromycin, metronidazole, levofloxacin and amoxicillin, often combined with a proton pump inhibitor (PPI). With the development of sequencing technologies, it has been demonstrated that not only does the colonization of the gastric and gut environment by H. pylori cause microbial changes, but also the treatment regimens used for its eradication have a significant altering effect on both the gastric and gut microbiota. Here, we review current knowledge on microbiota modulations of current therapies in both environments. We also summarize future perspectives regarding H. pylori infection, the integration of probiotics into therapy and what challenges are being faced on a global basis when we talk about eradication.
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Affiliation(s)
- Ege Tohumcu
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Francesco Kaitsas
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Ludovica Bricca
- Department of Surgical, Oncological and Gastroenterological Sciences (DiSCOG), Padua Univeristy, 35123 Padova, Italy;
| | - Alessandro Ruggeri
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Antonio Gasbarrini
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Giovanni Cammarota
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
| | - Gianluca Ianiro
- Department of Translational Medicine and Surgery, Università Cattolica del Sacro Cuore, Largo A. Gemelli 8, 00168 Rome, Italy; (E.T.); (F.K.); (A.R.); (A.G.); (G.C.)
- Department of Medical and Surgical Sciences, UOC Gastroenterologia, Fondazione Policlinico Universitario Agostino Gemelli IRCCS, 00168 Rome, Italy
- Department of Medical and Surgical Sciences, UOC CEMAD Centro Malattie dell’Apparato Digerente, Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, 00168 Rome, Italy
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8
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Jiang L, Song C, Ai C, Wen C, Song S. Modulation effect of sulfated polysaccharide from Sargassum fusiforme on gut microbiota and their metabolites in vitro fermentation. Front Nutr 2024; 11:1400063. [PMID: 38751743 PMCID: PMC11094809 DOI: 10.3389/fnut.2024.1400063] [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: 03/13/2024] [Accepted: 04/10/2024] [Indexed: 05/18/2024] Open
Abstract
The present study demonstrated the digestion behavior and fermentation characteristics of a sulfated polysaccharide from Sargassum fusiforme (SFSP) in the simulated digestion tract environment. The results showed that the molecular weight of two components in SFSP could not be changed by simulated digestion, and no free monosaccharide was produced. This indicates that most of SFSP can reach the colon as prototypes. During the fermentation with human intestinal flora in vitro, the higher-molecular-weight component of SFSP was utilized, the total sugar content decreased by 16%, the reducing sugar content increased, and the galactose content in monosaccharide composition decreased relatively. This indicates that SFSP can be selectively utilized by human intestinal flora. At the same time, SFSP also changed the structure of intestinal flora. Compared with the blank group, SFSP significantly increased the abundance of Bacteroidetes and decreased the abundance of Firmicutes. At the genus level, the abundances of Bacteroides and Megamonas increased, while the abundances of Shigella, Klebsiella, and Collinsella decreased. Moreover, the concentrations of total short-chain fatty acids (SCFAs), acetic, propionic and n-butyric acids significantly increased compared to the blank group. SFSP could down-regulate the contents of trimethylamine, piperidone and secondary bile acid in fermentation broth. The contents of nicotinic acid, pantothenic acid and other organic acids were increased. Therefore, SFSP shows significant potential to regulate gut microbiota and promote human health.
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Affiliation(s)
| | | | | | | | - Shuang Song
- SKL of Marine Food Processing and Safety Control, National Engineering Research Center of Seafood, Collaborative Innovation Center of Seafood Deep Processing, National and Local Joint Engineering Laboratory for Marine Bioactive Polysaccharide Development and Application, Liaoning Key Laboratory of Food Nutrition and Health, School of Food Science and Technology, Dalian Polytechnic University, Dalian, China
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9
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Elghannam MT, Hassanien MH, Ameen YA, Turky EA, ELattar GM, ELRay AA, ELTalkawy MD. Helicobacter pylori and oral-gut microbiome: clinical implications. Infection 2024; 52:289-300. [PMID: 37917397 PMCID: PMC10954935 DOI: 10.1007/s15010-023-02115-7] [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: 07/06/2023] [Accepted: 10/09/2023] [Indexed: 11/04/2023]
Abstract
More than half of the world's population are colonized with H. pylori; however, the prevalence varies geographically with the highest incidence in Africa. H. pylori is probably a commensal organism that has been associated with the development of gastritis, ulcers, and gastric cancer. H. pylori alone is most probably not enough for the development of gastric carcinoma, but evidence for its association with the disease is high and has, therefore, been classified by the International Agency for Research on Cancer as a Class 1 carcinogen. Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the oral-gut axis. The eradication therapy required to treat H. pylori infection can also have detrimental consequences for the gut microbiota, leading to a decreased alpha diversity. Therefore, therapy regimens integrated with probiotics may abolish the negative effects of antibiotic therapy on the gut microbiota. These eradication therapies combined with probiotics have also higher rates of eradication, when compared to standard treatments, and are associated with reduced side effects, improving the patient's compliance. The eradication therapy not only affects gut microbiome but also affects the oral microbiome with robust predominance of harmful bacteria. However, there have been reports of a protective role of H. pylori in Barrett's esophagus, esophageal adenocarcinoma, eosinophilic esophagitis, IBD, asthma, and even multiple sclerosis. Therefore, eradication therapy should be carefully considered, and test to treat policy should be tailored to specific communities especially in highly endemic areas. Supplementation of probiotics, prebiotics, herbals, and microbial metabolites to reduce the negative effects of eradication therapy should be considered. After failure of many eradication attempts, the benefits of H. pylori eradication should be carefully balanced against the risk of adverse effects especially in the elderly, persons with frailty, and intolerance to antibiotics.
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Affiliation(s)
- Maged T Elghannam
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt.
| | - Moataz H Hassanien
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Yosry A Ameen
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Emad A Turky
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Gamal M ELattar
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Ahmed A ELRay
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
| | - Mohammed D ELTalkawy
- Hepatogastroenterology Department, Theodor Bilharz Research Institute, Giza, Egypt
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10
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Sekaya G, Wang F, Brown H, Alagesan P, Batch BC, Garman K, Epplein M. Type 2 Diabetes Mellitus and Helicobacter pylori Eradication in a Clinical Population. South Med J 2024; 117:199-205. [PMID: 38569609 PMCID: PMC10997161 DOI: 10.14423/smj.0000000000001672] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/05/2024]
Abstract
OBJECTIVES Eradication of Helicobacter pylori reduces the risk of gastric cancer (GC). Individuals with type 2 diabetes mellitus (T2DM) are known to be at increased risk for GC. In a cohort of H. pylori-positive individuals, we assessed whether those with T2DM were at risk of persistent infection following H. pylori treatment compared with individuals without T2DM. METHODS A random subset of all individuals diagnosed as having H. pylori without intestinal metaplasia at endoscopy from 2015 to 2019 were stratified evenly by race (Black and White). After excluding those with T1DM and those without eradication testing after H. pylori treatment, logistic regression analysis was used to determine the association of T2DM with the risk of persistent H. pylori infection following treatment. RESULTS In 138 patients, H. pylori eradication rates did not differ between the 27% of individuals with T2DM compared to those without (81.1% vs 81.2%). After adjusting for age, race, and insurance status, we found no significant increased risk of persistent H. pylori infection for individuals with T2DM (odds ratio 1.40; 95% confidence interval 0.49-3.99). CONCLUSIONS H. pylori eradication rates do not differ by T2DM status, providing support for clinical trials of H. pylori eradication to reduce GC incidence among high-risk populations in the United States, such as individuals with T2DM.
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Affiliation(s)
- Grace Sekaya
- Department of Population Health Sciences, Duke University, Durham, North Carolina
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
- Frederick P. Whiddon College of Medicine, University of South Alabama, Mobile
| | - Frances Wang
- Department of Biostatistics & Bioinformatics, Duke University, Durham, North Carolina
| | - HannahSofia Brown
- Department of Medicine, Division of Gastroenterology, Duke University, Durham, North Carolina
| | - Priya Alagesan
- Department of Endocrinology and Metabolism, Duke University, Durham, North Carolina
| | - Bryan C. Batch
- Department of Endocrinology and Metabolism, Duke University, Durham, North Carolina
| | - Katherine Garman
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
- Department of Medicine, Division of Gastroenterology, Duke University, Durham, North Carolina
| | - Meira Epplein
- Department of Population Health Sciences, Duke University, Durham, North Carolina
- Cancer Risk, Detection, and Interception Program, Duke Cancer Institute, Durham, North Carolina
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11
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Wang X, Guo L, Qin T, Lai P, Jing Y, Zhang Z, Zhou G, Gao P, Ding G. Effects of X-ray cranial irradiation on metabolomics and intestinal flora in mice. ECOTOXICOLOGY AND ENVIRONMENTAL SAFETY 2024; 270:115898. [PMID: 38171101 DOI: 10.1016/j.ecoenv.2023.115898] [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: 01/21/2023] [Revised: 12/18/2023] [Accepted: 12/26/2023] [Indexed: 01/05/2024]
Abstract
Cranial radiotherapy is an important treatment for intracranial and head and neck tumors. To investigate the effects of cranial irradiation (C-irradiation) on gut microbiota and metabolomic profile, the feces, plasma and cerebral cortex were isolated after exposing mice to cranial X-ray irradiation at a dose rate of 2.33 Gy/min (5 Gy/d for 4 d consecutively). The gut microorganisms and metabolites were detected by 16 S rRNA gene sequencing method and LC-MS method, respectively. We found that compared with sham group, the gut microbiota composition changed at 2 W and 4 W after C-irradiation at the genus level. The fecal metabolomics showed that compared with Sham group, 44 and 66 differential metabolites were found to be annotated into metabolism pathways at 2 W and 4 W after C-irradiation, which were significantly enriched in the arginine and proline metabolism. Metabolome analysis of serum and cerebral cortex showed that, at 4 W after C-irradiation, the expression pattern of metabolites in serum samples of mice was similar to that of sham group, and the cerebral cortex metabolites of the two groups were completely separated. KEGG functional analysis showed that serum and brain tissue differential metabolites were respectively enriched in tryptophan metabolism, and arginine proline metabolism. The correlation analysis showed that the changes of gut microbiota genera were significantly correlated with the changes of metabolism, especially Helicobacter, which was significantly correlated with many different metabolites at 4 W after C-irradiation. These data suggested that C-irradiation could affect the gut microbiota and metabolism profile, even at relatively long times after C-irradiation.
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Affiliation(s)
- Xing Wang
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Ling Guo
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Tongzhou Qin
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Panpan Lai
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Yuntao Jing
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Zhaowen Zhang
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
| | - Guiqiang Zhou
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China; Department of Labor and Environmental Hygiene, School of public health, Weifang Medical University, Weifang, China.
| | - Peng Gao
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China
| | - Guirong Ding
- Department of Radiation Protection Medicine, School of Military Preventive Medicine, Air Force Medical University, Xi'an, China; Ministry of Education Key Lab of Hazard Assessment and Control in Special Operational Environment, Xi'an, China.
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12
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Chen Y, Qian XX. Gastric Helicobacter pylori infection does not contribute to extraoral halitosis and its eradication cannot achieve substantial reduction of halitosis. Helicobacter 2024; 29. [DOI: 10.1111/hel.13047] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/06/2023] [Accepted: 12/11/2023] [Indexed: 10/05/2024]
Abstract
AbstractBackgroundSome researchers have suggested that Helicobacter pylori (H. pylori) infection is attributed to extraoral halitosis. However, this viewpoint is increasingly challenged by clinical practice. This study was conducted with the aim of investigating changes of extraoral halitosis before and after H. pylori eradication.Materials and MethodsData of patients who had H. pylori infection and extraoral halitosis were retrospectively collected. H. pylori infection was diagnosed by positive 13C urea breath test (UBT). Extraoral halitosis was diagnosed by organoleptic score (OLS) ≥2 in nose breath. A 14‐day bismuth‐based quadruple therapy was administered for H. pylori eradication. Extraoral halitosis was examined before eradication (T1), on the first day after eradication (T2), 1 month after eradication (T3), and 3 months after eradication (T4). Eradication effect was checked by UBT at T3.ResultsA total of 100 patients were included. Eradication was successful in 74 out of 100 (74%) patients (success group) and failed in 26 out of 100 (26%) patients (failure group). 32 out of 74 (43.24%) patients in success group and 10 out of 26 (38.46%) patients in failure group had reduced halitosis at T2, 9 out of 74 (12.16%) patients in success group and 2 out 26 (7.69%) patients in failure group had relapsed halitosis at T3, and 23 out of 74 (31.08%) patients in success group and 8 out of 26 (30.77%) patients in failure group had relapsed halitosis at T4, without significant difference between groups at any time (p = 0.918, p = 0.808, and p = 0.808 respectively).ConclusionsHelicobacter pylori infection does not contribute to extraoral halitosis. H. pylori eradication can achieve sustained but slight reduction of extraoral halitosis, probably due to its antibiotic effects on the gut microbiota rather than H. pylori.
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Affiliation(s)
- Ying Chen
- Department of Gastroenterology, Minhang Hospital Fudan University Shanghai China
- Key Laboratory of Whole‐Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital Fudan University Shanghai China
| | - Xiao Xian Qian
- Department of Gastroenterology, Minhang Hospital Fudan University Shanghai China
- Key Laboratory of Whole‐Period Monitoring and Precise Intervention of Digestive Cancer, Shanghai Municipal Health Commission (SMHC), Minhang Hospital Fudan University Shanghai China
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13
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Chang A, Chang A, Chen WT, Chan L, Hong CT, Chien LN. Triple therapy for Helicobacter pylori eradication and the risk of hypoglycemia in patients with diabetes: a population-based cohort study. BMC Public Health 2023; 23:1772. [PMID: 37700268 PMCID: PMC10496377 DOI: 10.1186/s12889-023-16689-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Accepted: 09/04/2023] [Indexed: 09/14/2023] Open
Abstract
The incidence of type 2 diabetes mellitus has risen globally, from 108 million cases in 1980 to 422 million cases in 2014. Although controlling glycemic levels in patients with diabetes is crucial, insulin and sulfonylureas can cause hypoglycemic episodes and even potentially fatal events such as comas, seizures, life-threatening arrhythmias, and myocardial infarctions. Several antibiotics have been documented to cause hypoglycemic episodes; the use of antibiotics along with insulin or sulfonylureas might further increase the risk of hypoglycemia. Therefore, researchers must determine which antibiotics carry a risk of inducing severe hypoglycemic events. The prevalence of H. pylori infection remains high in most countries, and the infection is often treated with triple therapy involving amoxicillin, clarithromycin, and a proton pump inhibitor (PPI). Several case reports have reported that hypoglycemia can occur when used with patients who also take diabetes medication. Therefore, we hypothesized that patients with diabetes have an increased risk of hypoglycemic episodes when being treated with triple therapy for H. pylori infection. By analyzing medical records from Taiwan's National Health Insurance Research Database, we found a significant association between hypoglycemia and triple therapy treatment for diabetic patients with peptic ulcer disease. Prescribing triple therapy to patients with diabetes and peptic ulcers significantly increased the risk of a hypoglycemic episode (adjusted odds ratio [aOR] = 1.75, 95% confidence interval [CI]: 1.64 to 1.88, P < 0.001). Similarly, the highest aOR (5.77, 95% CI 4.82 to 6.92) was found in patients with diabetes and peptic ulcers who had hypoglycemic episodes within 30 days after triple therapy treatment. Many patients with diabetes require H.pylori eradication for peptic ulcer treatment, and vigilance toward the risk of hypoglycemia in this population is thus necessary.
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Affiliation(s)
- Anne Chang
- Department of Endocrinology, Shuang Ho Hospital, Taipei Medical University, New Taipei City, Taiwan
| | - Anna Chang
- Department of Neurology, Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan
| | - Wan-Ting Chen
- Health Data Analytics and Statistics Center, Taipei Medical University, Taipei, Taiwan
| | - Lung Chan
- Department of Neurology, Taipei Medical University-Shuang Ho Hospital, No. 291, Zhongzheng Rd, Zhonghe District, New Taipei City, 23561, Taiwan
| | - Chien-Tai Hong
- Department of Neurology, Taipei Medical University-Shuang Ho Hospital, No. 291, Zhongzheng Rd, Zhonghe District, New Taipei City, 23561, Taiwan.
- Department of Neurology, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
| | - Li-Nien Chien
- Institution of Health and Welfare Policy, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
- Graduate Institute of Data Science, College of Management, Taipei Medical University, Taipei, Taiwan.
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14
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Feilstrecker Balani G, dos Santos Cortez M, Picasky da Silveira Freitas JE, Freire de Melo F, Zarpelon-Schutz AC, Teixeira KN. Immune response modulation in inflammatory bowel diseases by Helicobacter pylori infection. World J Gastroenterol 2023; 29:4604-4615. [PMID: 37662864 PMCID: PMC10472898 DOI: 10.3748/wjg.v29.i30.4604] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/28/2023] [Revised: 07/01/2023] [Accepted: 07/24/2023] [Indexed: 08/10/2023] Open
Abstract
Many studies point to an association between Helicobacter pylori (H. pylori) infection and inflammatory bowel diseases (IBD). Although controversial, this association indicates that the presence of the bacterium somehow affects the course of IBD. It appears that H. pylori infection influences IBD through changes in the diversity of the gut microbiota, and hence in local chemical characteristics, and alteration in the pattern of gut immune response. The gut immune response appears to be modulated by H. pylori infection towards a less aggressive inflammatory response and the establishment of a targeted response to tissue repair. Therefore, a T helper 2 (Th2)/macrophage M2 response is stimulated, while the Th1/macrophage M1 response is suppressed. The immunomodulation appears to be associated with intrinsic factors of the bacteria, such as virulence factors - such oncogenic protein cytotoxin-associated antigen A, proteins such H. pylori neutrophil-activating protein, but also with microenvironmental changes that favor permanence of H. pylori in the stomach. These changes include the increase of gastric mucosal pH by urease activity, and suppression of the stomach immune response promoted by evasion mechanisms of the bacterium. Furthermore, there is a causal relationship between H. pylori infection and components of the innate immunity such as the NLR family pyrin domain containing 3 inflammasome that directs IBD toward a better prognosis.
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Affiliation(s)
| | | | | | - Fabrício Freire de Melo
- Campus Anísio Teixeira, Universidade Federal da Bahia, Instituto Multidisciplinar em Saúde, Vitória da Conquista 45.029-094, Bahia, Brazil
| | - Ana Carla Zarpelon-Schutz
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa de Pós-graduação em Biotecnologia - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
| | - Kádima Nayara Teixeira
- Campus Toledo, Universidade Federal do Paraná, Toledo 85.919-899, Paraná, Brazil
- Programa Multicêntrico de Pós-graduação em Bioquímica e Biologia Molecular - Setor Palotina, Universidade Federal do Paraná, Palotina 85.950-000, Paraná, Brazil
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15
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Gudra D, Silamikelis I, Pjalkovskis J, Danenberga I, Pupola D, Skenders G, Ustinova M, Megnis K, Leja M, Vangravs R, Fridmanis D. Abundance and prevalence of ESBL coding genes in patients undergoing first line eradication therapy for Helicobacter pylori. PLoS One 2023; 18:e0289879. [PMID: 37561723 PMCID: PMC10414638 DOI: 10.1371/journal.pone.0289879] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/05/2022] [Accepted: 07/28/2023] [Indexed: 08/12/2023] Open
Abstract
The spread of extended-spectrum beta-lactamases (ESBLs) in nosocomial and community-acquired enterobacteria is an important challenge for clinicians due to the limited therapeutic options for infections that are caused by these organisms. Here, we developed a panel of ESBL coding genes, evaluated the abundance and prevalence of ESBL encoding genes in patients undergoing H. pylori eradication therapy, and summarized the effects of eradication therapy on functional profiles of the gut microbiome. To assess the repertoire of known beta lactamase (BL) genes, they were divided into clusters according to their evolutionary relation. Primers were designed for amplification of cluster marker regions, and the efficiency of this amplification panel was assessed in 120 fecal samples acquired from 60 patients undergoing H. pylori eradication therapy. In addition, fecal samples from an additional 30 patients were used to validate the detection efficiency of the developed ESBL panel. The presence for majority of targeted clusters was confirmed by NGS of amplification products. Metagenomic sequencing revealed that the abundance of ESBL genes within the pool of microorganisms was very low. The global relative abundances of the ESBL-coding gene clusters did not differ significantly among treatment states. However, at the level of each cluster, classical ESBL producers such as Klebsiella sp. for blaOXY (p = 0.0076), Acinetobacter sp. for blaADC (p = 0.02297) and others, differed significantly with a tendency to decrease compared to the pre- and post-eradication states. Only 13 clusters were common across all three datasets, suggesting a patient-specific distribution profile of ESBL-coding genes. The number of AMR genes detected in the post-eradication state was higher than that in the pre-eradication state, which could be attributed, at least in part, to the therapy. This study demonstrated that the ESBL screening panel was effective in targeting ESBL-coding gene clusters from bacterial DNA and that minor differences exist in the abundance and prevalence of ESBL-coding gene levels before and after eradication therapy.
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Affiliation(s)
- Dita Gudra
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | | | | | | | - Darta Pupola
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Girts Skenders
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Maija Ustinova
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Kaspars Megnis
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
- Faculty of Medicine, University of Latvia, Riga, Latvia
| | - Reinis Vangravs
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
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16
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Wang R, Huang S, Gan P, Pan X, Wang P, Zhong X, Lü M, Zhou X, Tang X. States and hotspots in Helicobacter pylori research from 2002 to 2021: A bibliometric analysis. Helicobacter 2023; 28:e12986. [PMID: 37133423 DOI: 10.1111/hel.12986] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/14/2022] [Revised: 03/26/2023] [Accepted: 04/01/2023] [Indexed: 05/04/2023]
Abstract
BACKGROUND Recently, numerous publications on Helicobacter pylori (H. pylori) have been published, but bibliometric analyses on this research field are scarce. To address this gap, we conducted a bibliometric analysis to provide a comprehensive overview and to explore the current research states and hotspots in this field. MATERIALS AND METHODS Publications on H. pylori from 2002 to 2021 were retrieved from the Web of Science Core Collection database (WoSCC). Trends in publications and citations were analyzed using Excel 2021. VOSviewer and Citespace were used to perform bibliometrics analysis. RESULTS 36,266 publications on H. pylori were retrieved from the WoSCC database. In general, we observed an increasing trend in the number of publications over the past 20 years. The United States was the most productive and influential country, with the largest proportion of both publications and total citations. Helicobacter, US Department of Veterans Affairs, and Graham, David were the most productive journals, institutions and authors, respectively. Further analysis the co-occurrence and burst detection of keywords revealed that the most common keywords were "Helicobacter pylori," "gastric cancer," and "gastritis," all keywords were divided into eight main clusters, and the most important current research hotspot was the relationship between H. pylori infection and the changes of gut microbiota. CONCLUSIONS The United States has been the most productive and influential country on H. pylori research, and H. pylori-related research remains an active research field. The relationship between H. pylori infection and the changes of gut microbiota is a research hotspot attracting significant attention.
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Affiliation(s)
- Ruiyu Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Shu Huang
- Department of Gastroenterology, Lianshui County People' Hospital, Huaian, China
- Department of Gastroenterology, Lianshui People' Hospital of Kangda College Affiliated to Nanjing Medical University, Huaian, China
| | - Peiling Gan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Xiao Pan
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Ping Wang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Xiaolin Zhong
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Muhan Lü
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Xian Zhou
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
| | - Xiaowei Tang
- Department of Gastroenterology, The Affiliated Hospital of Southwest Medical University, Luzhou, China
- Nuclear Medicine and Molecular Imaging Key Laboratory of Sichuan Province, Luzhou, China
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Tawfik SA, Azab M, Ramadan M, Shabayek S, Abdellah A, Al Thagfan SS, Salah M. The Eradication of Helicobacter pylori Was Significantly Associated with Compositional Patterns of Orointestinal Axis Microbiota. Pathogens 2023; 12:832. [PMID: 37375522 DOI: 10.3390/pathogens12060832] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/10/2023] [Revised: 06/10/2023] [Accepted: 06/12/2023] [Indexed: 06/29/2023] Open
Abstract
BACKGROUND Helicobacter pylori (H. pylori) is significantly linked to various diseases that seriously impact human health, such as gastric ulcers, chronic gastritis and gastric adenocarcinoma. METHODS The compositional shifts in bacterial communities of the orointestinal axis were surveyed pre/post-eradication of H. pylori. In total, 60 samples, including stool and salivary specimens, were collected from 15 H. pylori-positive individuals (HPP) before beginning and 2 months after receiving the eradication therapy. The V3-V4 regions of the 16S rRNA gene were sequenced using MiSeq. RESULTS Overall, oral microbiomes were collectively more diverse than the gut microbiomes (Kruskal-Wallis; p = 3.69 × 10-5). Notably, the eradication of H. pylori was associated with a significant reduction in the bacterial diversity along the orointestinal axis (Wilcoxon rank sum test; p = 6.38 × 10-3). Interestingly, the oral microbiome of HPP showed a positive correlation between Proteobacteria and Fusobacteria, in addition to a significant predominance of Streptococcus, in addition to Eubacterium_eligens, Haemophilus, Ruminococcaceae, Actinomyces and Staphylococcus. On the other hand, Fusobacterium, Veillonella, Catenibacterium, Neisseria and Prevotella were significantly enriched upon eradication of H. pylori. Generally, Bacteroidetes and Fusobacteria positively coexisted during H. pylori infection along the orointestinal axis (r = 0.67; p = 0.0006). The eradication of H. pylori was positively linked to two distinctive orotypes (O3 and O4). Orotype O4 was characterized by a robust abundance of Veillonella and Fusobacteria. The gut microbiomes during H. pylori infection showed a remarkable predominance of Clostridium_sensu_stricto_1 and Escherichia_Shigella. Likewise, Bifidobacterium and Faecalibacterium were significantly enriched upon eradication of H. pylori. CONCLUSIONS Finally, the impact of eradication therapy clearly existed on the representation of certain genera, especially in the oral microbiome, which requires particular concern in order to counteract and limit their subsequent threats.
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Affiliation(s)
- Sally Ali Tawfik
- Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Marwa Azab
- Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Mohammed Ramadan
- Department of Microbiology and Immunology, Faculty of Pharmacy, Al-Azhar University, Assiut 71524, Egypt
| | - Sarah Shabayek
- Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Ali Abdellah
- Department of Microbiology and Immunology, Faculty of Pharmacy, Suez Canal University, Ismailia 41522, Egypt
| | - Sultan S Al Thagfan
- Department of Clinical and Hospital Pharmacy, College of Pharmacy, Taibah University, Al Madinah Al Munaearah 42353, Saudi Arabia
| | - Mohammed Salah
- Department of Microbiology and Immunology, Faculty of Pharmacy, Port Said University, Port Said 42511, Egypt
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18
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Zang H, Wang J, Wang H, Guo J, Li Y, Zhao Y, Song J, Liu F, Liu X, Zhao Y. Metabolic alterations in patients with Helicobacter pylori-related gastritis: The H. pylori-gut microbiota-metabolism axis in progression of the chronic inflammation in the gastric mucosa. Helicobacter 2023:e12984. [PMID: 37186092 DOI: 10.1111/hel.12984] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/04/2022] [Revised: 02/15/2023] [Accepted: 03/13/2023] [Indexed: 05/17/2023]
Abstract
PURPOSE To characterize the serum metabolism in patients with Helicobacter pylori-positive and H. pylori-negative gastritis. METHODS Clinical data and serum gastric function parameters, PGI (pepsinogen I), PGII, PGR (PGI/II), and G-17 (gastrin-17) of 117 patients with chronic gastritis were collected, including 57 H. pylori positive and 60 H. pylori negative subjects. Twenty cases in each group were randomly selected to collect intestinal mucosa specimens and serum samples. The gut microbiota profiles were generated by 16S rRNA gene sequencing, and the serum metabolites were analyzed by a targeted metabolomics approach based on liquid chromatography-mass spectrometry (LC-MS) technology. RESULTS Altered expression of 20 metabolites, including isovaleric acid, was detected in patients with HPAG. Some taxa of Bacteroides, Fusobacterium, and Prevotella in the gut microbiota showed significant correlations with differentially expressed metabolites between H. pylori positive and H. pylori negative individuals. As a result, an H. pylori-gut microbiota-metabolism (HGM) axis was proposed. CONCLUSION Helicobacter pylori infection may influence the progression of mucosal diseases and the emergence of other complications in the host by altering the gut microbiota, and thus affecting the host serum metabolism.
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Affiliation(s)
- Hongmin Zang
- Hebei University of Chinese Medicine, Shijiazhuang, China
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Jin Wang
- Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Huijie Wang
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Jiaxuan Guo
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Yuchan Li
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Yinuo Zhao
- School of Biological Sciences, Faculty of Biology, Medicine and Health, The University of Manchester, Manchester, UK
| | - Jinzhong Song
- Hebei University of Chinese Medicine, Shijiazhuang, China
- The Traditional Chinese Medicine Hospital of Shijiazhuang, Shijiazhuang, China
| | - Fengshuang Liu
- Hebei University of Chinese Medicine, Shijiazhuang, China
- Hebei Academy of Traditional Chinese Medicine, Shijiazhuang, China
| | - Xuzhao Liu
- North China University of Science and Technology, Tangshan, China
| | - Yubin Zhao
- Hebei University of Chinese Medicine, Shijiazhuang, China
- North China University of Science and Technology, Tangshan, China
- Shijiazhuang People's Hospital, Shijiazhuang, China
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19
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Wang L, Yao H, Morgan DC, Lau KS, Leung SY, Ho JWK, Leung WK. Altered human gut virome in patients undergoing antibiotics therapy for Helicobacter pylori. Nat Commun 2023; 14:2196. [PMID: 37069161 PMCID: PMC10110541 DOI: 10.1038/s41467-023-37975-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2022] [Accepted: 04/04/2023] [Indexed: 04/19/2023] Open
Abstract
Transient gut microbiota alterations have been reported after antibiotic therapy for Helicobacter pylori. However, alteration in the gut virome after H. pylori eradication remains uncertain. Here, we apply metagenomic sequencing to fecal samples of 44 H. pylori-infected patients at baseline, 6-week (N = 44), and 6-month (N = 33) after treatment. Following H. pylori eradication, we discover contraction of the gut virome diversity, separation of virome community with increased community difference, and shifting towards a higher proportion of core virus. While the gut microbiota is altered at 6-week and restored at 6-month, the virome community shows contraction till 6-month after the treatment with enhanced phage-bacteria interactions at 6-week. Multiple courses of antibiotic treatments further lead to lower virus community diversity when compared with treatment naive patients. Our results demonstrate that H. pylori eradication therapies not only result in transient alteration in gut microbiota but also significantly alter the previously less known gut virome community.
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Affiliation(s)
- Lingling Wang
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Haobin Yao
- School of Biomedical Science, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China
| | - Daniel C Morgan
- School of Biomedical Science, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China
| | - Kam Shing Lau
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China
| | - Suet Yi Leung
- Centre for PanorOmic Sciences (CPOS), The University of Hong Kong, Pokfulam, Hong Kong, China
- Department of Pathology, The University of Hong Kong, Queen Mary Hospital, Pokfulam, Hong Kong, China
- The Jockey Club Centre for Clinical Innovation and Discovery, LKS Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Joshua W K Ho
- School of Biomedical Science, The University of Hong Kong, Hong Kong, China
- Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China
- Centre for PanorOmic Sciences (CPOS), The University of Hong Kong, Pokfulam, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, School of Clinical Medicine, The University of Hong Kong, Hong Kong, China.
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20
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Palacios E, Lobos-González L, Guerrero S, Kogan MJ, Shao B, Heinecke JW, Quest AFG, Leyton L, Valenzuela-Valderrama M. Helicobacter pylori outer membrane vesicles induce astrocyte reactivity through nuclear factor-κappa B activation and cause neuronal damage in vivo in a murine model. J Neuroinflammation 2023; 20:66. [PMID: 36895046 PMCID: PMC9996972 DOI: 10.1186/s12974-023-02728-7] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2022] [Accepted: 02/10/2023] [Indexed: 03/11/2023] Open
Abstract
BACKGROUND Helicobacter pylori (Hp) infects the stomach of 50% of the world's population. Importantly, chronic infection by this bacterium correlates with the appearance of several extra-gastric pathologies, including neurodegenerative diseases. In such conditions, brain astrocytes become reactive and neurotoxic. However, it is still unclear whether this highly prevalent bacterium or the nanosized outer membrane vesicles (OMVs) they produce, can reach the brain, thus affecting neurons/astrocytes. Here, we evaluated the effects of Hp OMVs on astrocytes and neurons in vivo and in vitro. METHODS Purified OMVs were characterized by mass spectrometry (MS/MS). Labeled OMVs were administered orally or injected into the mouse tail vein to study OMV-brain distribution. By immunofluorescence of tissue samples, we evaluated: GFAP (astrocytes), βIII tubulin (neurons), and urease (OMVs). The in vitro effect of OMVs in astrocytes was assessed by monitoring NF-κB activation, expression of reactivity markers, cytokines in astrocyte-conditioned medium (ACM), and neuronal cell viability. RESULTS Urease and GroEL were prominent proteins in OMVs. Urease (OMVs) was present in the mouse brain and its detection coincided with astrocyte reactivity and neuronal damage. In vitro, OMVs induced astrocyte reactivity by increasing the intermediate filament proteins GFAP and vimentin, the plasma membrane αVβ3 integrin, and the hemichannel connexin 43. OMVs also produced neurotoxic factors and promoted the release of IFNγ in a manner dependent on the activation of the transcription factor NF-κB. Surface antigens on reactive astrocytes, as well as secreted factors in response to OMVs, were shown to inhibit neurite outgrowth and damage neurons. CONCLUSIONS OMVs administered orally or injected into the mouse bloodstream reach the brain, altering astrocyte function and promoting neuronal damage in vivo. The effects of OMVs on astrocytes were confirmed in vitro and shown to be NF-κB-dependent. These findings suggest that Hp could trigger systemic effects by releasing nanosized vesicles that cross epithelial barriers and access the CNS, thus altering brain cells.
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Affiliation(s)
- Esteban Palacios
- Laboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de La Salud, Universidad Central de Chile, 8330546, Santiago, Chile.,Laboratory of Cellular Communication, Center for Studies On Exercise Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile.,Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile
| | - Lorena Lobos-González
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.,Centro de Medicina Regenerativa, Facultad de Medicina, Universidad del Desarrollo-Clínica Alemana, 7590943, Santiago, Chile
| | - Simón Guerrero
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.,Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.,Facultad de Medicina, Universidad de Atacama, 153601, Copiapó, Chile
| | - Marcelo J Kogan
- Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.,Departamento de Química Farmacológica y Toxicológica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile
| | - Baohai Shao
- Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, 98195-8055, USA
| | - Jay W Heinecke
- Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, WA, 98195-8055, USA
| | - Andrew F G Quest
- Laboratory of Cellular Communication, Center for Studies On Exercise Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile.,Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile
| | - Lisette Leyton
- Laboratory of Cellular Communication, Center for Studies On Exercise Metabolism and Cancer (CEMC), Institute of Biomedical Sciences (ICBM), Facultad de Medicina, Universidad de Chile, 8380453, Santiago, Chile. .,Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.
| | - Manuel Valenzuela-Valderrama
- Laboratorio de Microbiología Celular, Instituto de Investigación y Postgrado, Facultad de Ciencias de La Salud, Universidad Central de Chile, 8330546, Santiago, Chile. .,Advanced Center for Chronic Diseases (ACCDiS), Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, 8380494, Santiago, Chile.
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21
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Lee S, Choi A, Park KH, Lee S, Yoon H, Kim P. Single-cell hemoprotein (heme-SCP) exerts the prebiotic potential to establish a healthy gut microbiota in small pet dogs. Food Sci Biotechnol 2023; 32:489-496. [PMID: 36911324 PMCID: PMC9992493 DOI: 10.1007/s10068-022-01195-9] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 10/08/2022] [Accepted: 10/24/2022] [Indexed: 11/25/2022] Open
Abstract
To investigate the effect of the single-cell hemoprotein (heme-SCP) source on animals, a dog-treat (100 g for each dog) harboring 0.2% heme-SCP was manufactured and fed to seven pet dogs (< 10 kg) in a randomized manner (irrespective of owner's feeding style, dogs' health conditions, and staple diets), and the feces before and after the dog-treat diet were analyzed to define the structure of the microbiota. The total bacterial species of the seven dogs showed no difference (564-584), although the bacterial compositions varied significantly. The Firmicutes phylum increased (54.7-73.7%), showing differential species composition before and after heme-SCP intake. Proteobacteria, Bacteroidetes, and Fusobacteria decreased (5.4-3.8%, 32.9-16.8%, and 6.3-3.6%, respectively), which agreed with the previous observation of deliberate feeding. Therefore, it is conceivable that heme-SCP as a prebiotic can shape the gut microbiota regardless of the administration method. Supplementary Information The online version contains supplementary material available at 10.1007/s10068-022-01195-9.
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Affiliation(s)
- Seungki Lee
- Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi 14662 South Korea
| | - Ahyoung Choi
- Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi 14662 South Korea
| | | | - Seoyeon Lee
- Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, Gyeonggi 16499 South Korea
| | - Hyunjin Yoon
- Department of Molecular Science and Technology, Ajou University, 206 World cup-ro, Yeongtong-gu, Suwon, Gyeonggi 16499 South Korea
| | - Pil Kim
- Department of Biotechnology, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon, Gyeonggi 14662 South Korea.,HemoLab Ltd. Co., Bucheon, 14622 South Korea
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22
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Du L, Chen B, Cheng F, Kim J, Kim JJ. Effects of Helicobacter pylori Therapy on Gut Microbiota: A Systematic Review and Meta-Analysis. Dig Dis 2022; 42:102-112. [PMID: 36228588 DOI: 10.1159/000527047] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/11/2021] [Accepted: 09/04/2022] [Indexed: 02/02/2023]
Abstract
BACKGROUND Although indications for evaluation and treatment of Helicobacter pylori infection are broadening to include primary prevention for gastric adenocarcinoma, potential adverse effects on gut microbiota have been raised. We performed a systematic review and meta-analysis to evaluate the effects of H. pylori therapy on gut microbiota. METHODS PubMed, EMBASE, Cochrane Library, and Web of Science (to 4/2021) were searched for studies quantitatively evaluating microbiota before and after H. pylori therapy. Meta-analysis was performed to assess early (<1 year) and long-term (≥1 year) effects on gut microbiota after H. pylori treatment. Subgroup analysis evaluating the effects of H. pylori therapy with addition of probiotics on gut microbiota was also performed. RESULTS Thirty studies (N = 1,218) met the criteria. Early after H. pylori therapy, intestinal microbial diversity was reduced in nearly all studies. At the genus level, reduction in the abundance of Enterococcus, while increase in Lactobacillus, Bifidobacterium, and Bacteroides counts were observed. However, Enterococcus, Lactobacillus, Bifidobacterium, and Bacteroides counts remained stable in patients who received probiotics with H. pylori therapy. At the phylum level, the relative abundance of Actinobacteria and Firmicutes increased after treatment. At ≥1 year, intestinal microbial diversity normalized in six of seven studies. No differences in the relative abundance of Actinobacteria, Firmicute, Bacteroidetes, and Proteobacteria were observed ≥1 year after therapy. CONCLUSION The impact of H. pylori therapy on gut microbiota appears transient with early changes largely resolving after 1 year. Probiotics may reduce the early impact of H. pylori therapy on gut microbiota.
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Affiliation(s)
- Lijun Du
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China,
| | - Binrui Chen
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Fangli Cheng
- Department of Gastroenterology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, China
| | - Jeffrey Kim
- Department of Family Medicine, Loma Linda University Health, Loma Linda, California, USA
| | - John J Kim
- Division of Gastroenterology, Loma Linda University Health, Loma Linda, California, USA
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23
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Chen X, Wang N, Wang J, Liao B, Cheng L, Ren B. The interactions between oral-gut axis microbiota and Helicobacter pylori. Front Cell Infect Microbiol 2022; 12:914418. [PMID: 35992177 PMCID: PMC9381925 DOI: 10.3389/fcimb.2022.914418] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2022] [Accepted: 07/14/2022] [Indexed: 11/13/2022] Open
Abstract
In the human body, each microbial habitat exhibits a different microbial population pattern, and these distinctive microflorae are highly related to the development of diseases. The microbial interactions from host different niches are becoming crucial regulators to shape the microbiota and their physiological or pathological functions. The oral cavity and gut are the most complex and interdependent microbial habitats. Helicobacter pylori is one of the most important pathogens from digestive tract, especially the stomach, due to its direct relationships with many gastric diseases including gastric cancer. H. pylori infections can destroy the normal gastric environment and make the stomach a livable channel to enhance the microbial interactions between oral cavity and gut, thus reshaping the oral and gut microbiomes. H. pylori can be also detected in the oral and gut, while the interaction between the oral-gut axis microbiota and H. pylori plays a major role in H. pylori’s colonization, infection, and pathogenicity. Both the infection and eradication of H. pylori and its interaction with oral-gut axis microbiota can alter the balance of the microecology of the oral-gut axis, which can affect the occurrence and progress of related diseases. The shift of oral-gut axis microbiota and their interactions with H. pylori maybe potential targets for H. pylori infectious diagnosis and treatment.
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Affiliation(s)
- Xi Chen
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
| | - Nanxi Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Jiannan Wang
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Binyou Liao
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
| | - Lei Cheng
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- Department of Operative Dentistry and Endodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Lei Cheng, ; Biao Ren,
| | - Biao Ren
- State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China School of Stomatology, Sichuan University, Chengdu, China
- *Correspondence: Lei Cheng, ; Biao Ren,
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24
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Hu Y, Xu X, Ouyang YB, He C, Li NS, Xie C, Peng C, Zhu ZH, Shu X, Xie Y, Lu NH, Zhu Y. Altered Gut Microbiota and Short-Chain Fatty Acids After Vonoprazan-Amoxicillin Dual Therapy for Helicobacter pylori Eradication. Front Cell Infect Microbiol 2022; 12:881968. [PMID: 35719338 PMCID: PMC9201212 DOI: 10.3389/fcimb.2022.881968] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2022] [Accepted: 05/09/2022] [Indexed: 12/17/2022] Open
Abstract
The combination of vonoprazan (VPZ) and amoxicillin (VA therapy) has been shown to achieve acceptable eradication rates for Helicobacter pylori (H. pylori). Herein, our aim was to explore the short-term effect of VA therapy on the gut microbiota and short-chain fatty acids (SCFAs) using human fecal samples. A total of 119 H. pylori-positive patients were randomized into low- or high-dose VA therapy (i.e., amoxicillin 1 g b.i.d. or t.i.d. and VPZ 20 mg b.i.d.) for 7 or 10 days. Thirteen H. pylori-negative patients served as controls. Fecal samples were collected from H. pylori-positive and H. pylori-negative patients. The gut microbiota and SCFAs were analyzed using 16S rRNA gene sequencing and gas chromatography-mass spectrometry, respectively. The gut microbiota in H. pylori-positive patients exhibited increased richness, diversity, and better evenness than matched patients. Fifty-three patients studied before and after H. pylori eradication were divided into low (L-VA) and high (H-VA) amoxicillin dose groups. The diversity and composition of the gut microbiota among L-VA patients exhibited no differences at the three time points. However, among H-VA patients, diversity was decreased, and the microbial composition was altered immediately after H-VA eradication but was restored by the confirmation time point. The decreased abundance of Anaerostipes, Dialister, and Lachnospira induced by H-VA was associated with altered SCFA levels. VA dual therapy for H. pylori eradication has minimal negative effects on gut microbiota and SCFAs.
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Affiliation(s)
- Yi Hu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Xin Xu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Yao-Bin Ouyang
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Cong He
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Nian-Shuang Li
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Chuan Xie
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Chao Peng
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Zhen-Hua Zhu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Xu Shu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Yong Xie
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Nong-Hua Lu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
| | - Yin Zhu
- Department Of Gastroenterology, The First Affiliated Hospital of Nanchang University, Nanchang, China
- JiangXi Clinical Research Center for Gastroenterology, Nanchang, China
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25
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Kim WS, Choi Y, Kim N, Lim SH, Noh G, Kim KW, Park J, Jo H, Yoon H, Shin CM, Park YS, Lee DH. Long-term effect of the eradication of Helicobacter pylori on the hemoglobin A1c in type 2 diabetes or prediabetes patients. Korean J Intern Med 2022; 37:579-590. [PMID: 34991230 PMCID: PMC9082431 DOI: 10.3904/kjim.2021.194] [Citation(s) in RCA: 7] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/18/2021] [Accepted: 10/25/2021] [Indexed: 11/27/2022] Open
Abstract
BACKGROUND/AIMS The long-term effect of Helicobacter pylori eradication on the metabolic syndrome or diabetes are unclear. The aim of this study was to evaluate the effect of H. pylori eradication on glycemic control in type 2 diabetes mellitus (T2DM) or prediabetes mellitus (preDM). METHODS A total of 124 asymptomatic subjects with T2DM or preDM were divided into H. pylori-negative (n = 40), H. pylori-positive with non-eradicated (n = 34), and eradicated (n = 50) groups. We measured H. pylori status (culture, histology, and rapid urease test) and glycated hemoglobin A1c (A1C) levels and followed-up at the 1st year and the 5th year of follow-up. RESULTS The A1C levels significantly decreased in the eradicated group compared to the negative group and the non-eradicated groups (at the 1st year, p = 0.024; at the 5th year, p = 0.009). The A1C levels decreased in male, and/or subjects < 65 years of age in subgroup analyses (in male subjects, p = 0.047 and p = 0.020 at the 1st and the 5th year; in subjects < 65 years of age, p = 0.028 and p = 0.006 at the 1st and the 5th year; in male subjects < 65 years of age, p = 0.039 and p = 0.032 at the 1st and the 5th year). The eradication of H. pylori was related to the decrease in A1C values throughout the follow-up period, compared to the non-eradicated group (p = 0.017). CONCLUSION H. pylori eradication was related to the decreasing of A1C levels in patients with T2DM or preDM over a long-term follow-up period, especially in male and subjects < 65 years of age.
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Affiliation(s)
- Won Seok Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Yonghoon Choi
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Nayoung Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Seon Hee Lim
- Department of Internal Medicine, Seoul National University Hospital Healthcare System Gangnam Center and Healthcare Research Institute, Seoul, Korea
| | - Gitark Noh
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Ki Wook Kim
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Jaehyung Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyeongho Jo
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Hyuk Yoon
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Cheol Min Shin
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Young Soo Park
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
| | - Dong Ho Lee
- Department of Internal Medicine, Seoul National University Bundang Hospital, Seongnam, Korea
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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26
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Ju Z, Shen L, Zhou M, Luo J, Yu Z, Qu C, Lei R, Lei M, Huang R. Helicobacter pylori and Alzheimer's Disease-Related Metabolic Dysfunction: Activation of TLR4/Myd88 Inflammation Pathway from p53 Perspective and a Case Study of Low-Dose Radiation Intervention. ACS Chem Neurosci 2022; 13:1065-1081. [PMID: 35312296 DOI: 10.1021/acschemneuro.2c00082] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/16/2022] Open
Abstract
Gut dysbiosis is observed in Alzheimer's disease (AD) and is frequently associated with AD-induced metabolic dysfunction. However, the extent and specific underlying molecular mechanisms triggered by alterations of gut microbiota composition and function mediating AD-induced metabolic dysfunction in AD remain incompletely uncovered. Here, we indicate that Helicobacter pylori (H. pylori) is abundant in AD patients with relative metabolic dysfunction. Fecal microbiota transplantation from the AD patients promoted metabolic dysfunction in mice and increased gut permeability. H. pylori increased gut permeability through activation of the TLR4/Myd88 inflammation pathway in a p53-dependent manner, leading to metabolic dysfunction. Moreover, p53 deficiency reduced bile acid concentration, leading to an increased abundance of H. pylori colonization. Overall, these data identify H. pylori as a key promoter of AD-induced metabolic dysfunction.
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Affiliation(s)
- Zhao Ju
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Liangfang Shen
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Meiling Zhou
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Jinhua Luo
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Zijian Yu
- The First Affiliated Hospital, University of South China, 69 Chuanshan Road, Hengyang, Hunan 421001, People’s Republic of China
| | - Can Qu
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Ridan Lei
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
| | - Mingjun Lei
- Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China
| | - Ruixue Huang
- Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha, Hunan 410078, China
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27
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Qiang L, Hu J, Tian M, Li Y, Ren C, Deng Y, Jiang Y. Extracellular vesicles from helicobacter pylori-infected cells and helicobacter pylori outer membrane vesicles in atherosclerosis. Helicobacter 2022; 27:e12877. [PMID: 35099837 DOI: 10.1111/hel.12877] [Citation(s) in RCA: 19] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 12/26/2021] [Accepted: 01/11/2022] [Indexed: 12/15/2022]
Abstract
BACKGROUND The role of H. pylori infection has been reported in various extragastric diseases, particularly, the correlation between H. pylori and atherosclerosis (AS) have received lots of attention. Some scholars demonstrated that the presence of H. pylori-specific DNA in the sclerotic plaques of atheromatous patients provides biological evidences, with indicating that H. pylori infection is a potential factor of AS. However, the underlying mechanism of H. pylori or their products cross the epithelial barriers to enter the blood circulation remains unclear. Recent studies have shown that the extracellular vesicles (EVs) derived from H. pylori-infected gastric epithelial cells encapsulated H. pylori virulence factor cytotoxin-associated gene A (CagA) and existed in the blood samples of patients or mice, which indicating that they can carry CagA into the blood circulation. Based on these findings, some researchers proposed a hypothesis that H. pylori is involved in the pathogenesis of AS via EVs-based mechanisms. In addition, outer membrane vesicles (OMVs) serve as transport vehicles to deliver H. pylori virulence factors to epithelial cells. It is necessary to discuss the role of H. pylori OMVs in the development of AS. OBJECTIVES This review will focus on the correlation between H. pylori infection and AS and tried to unveil the possible role of EVs from H. pylori-infected cells and H. pylori OMVs in the pathogenesis of AS, with a view to providing help in refining our knowledge in this aspect. METHODS All of information included in this review was retrieved from published studies on H. pylori infection in AS. RESULTS H. pylori infection may be an atherosclerotic risk factor and drives researchers to reevaluate the role of H. pylori in the pathogenesis of AS. Some findings proposed a new hypothesis that H. pylori may be involved in the pathogenesis of AS through EVs-based mechanisms. Besides EVs from H. pylori-infected cells, whether H. pylori OMVs may play some role in the pathogenesis of AS is still remain unclear. CONCLUSION Existing epidemiological and clinical evidence had shown that there is a possible association between H. pylori and AS. However, except for the larger randomized controlled trials, more basic research about EVs from H. pylori-infected cells and H. pylori OMVs is the need of the hour to unveil the possible role of H. pylori infection in the pathogenesis of AS.
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Affiliation(s)
- Liming Qiang
- Department of Gastroenterology, West China-Guang'an Hospital, Sichuan University, Guang'an, China
| | - Jianguo Hu
- Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, China
| | - Mingyuan Tian
- Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Yu Li
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Chao Ren
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yi Deng
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
| | - Yuan Jiang
- Clinical Medical College, The First Affiliated Hospital of Chengdu Medical College, Chengdu, China
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Wang L, Yao H, Tong T, Lau K, Leung SY, Ho JWK, Leung WK. Dynamic changes in antibiotic resistance genes and gut microbiota after Helicobacter pylori eradication therapies. Helicobacter 2022; 27:e12871. [PMID: 34969161 DOI: 10.1111/hel.12871] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2021] [Revised: 12/08/2021] [Accepted: 12/14/2021] [Indexed: 12/19/2022]
Abstract
BACKGROUND Short-term antibiotics exposure is associated with alterations in microbiota and antibiotic resistance genes (ARGs) in the human gut. While antibiotics are critical in the successful eradication of Helicobacter pylori, the short-term and long-term impacts on the composition and quantity of antibiotics resistance genes after H. pylori eradication are unclear. This study used whole-genome shotgun metagenomic of stool samples to characterize the gut microbiota and ARGs, before and after H. pylori eradication therapy. RESULTS Forty-four H. pylori-infected patients were recruited, including 21 treatment naïve patients who received clarithromycin-based triple therapy (CLA group) and 23 patients who failed previous therapies, in which 10 received levofloxacin-based quadruple therapy (LEVO group) and 13 received other combinations (OTHER group). Stool samples were collected at baseline (before current treatment), 6 week and 6 month after eradication therapy. At baseline, there was only a slight difference among the three groups on ARGs and gut microbiota. After eradication therapy, there was a transient but significant increase in gut ARGs 6 week post-therapy, among which the LEVO group had the most significant ARGs alteration compared to other two groups. For treatment naïve patients, those with higher ErmF abundance were prone to fail CLA eradication and gain more ARGs after treatment. For gut microbiota, the bacteria richness decreased at 6 week and there was a significant difference in microbiota community among the three groups at 6 week. CONCLUSIONS Our findings demonstrated the dynamic alterations in gut microbiota and ARGs induced by different eradication therapies, which could influence the choices of antibiotics in eradication therapy.
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Affiliation(s)
- Lingling Wang
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Haobin Yao
- School of Biomedical Science, The University of Hong Kong, Hong Kong, China.,Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China
| | - Teresa Tong
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - KamShing Lau
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Suet Yi Leung
- Centre for PanorOmic Sciences (CPOS), The University of Hong Kong, Hong Kong, China.,Department of Pathology, Queen Mary Hospital, The University of Hong Kong, Hong Kong, China.,The Jockey Club Centre for Clinical Innovation and Discovery, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong, China
| | - Joshua W K Ho
- School of Biomedical Science, The University of Hong Kong, Hong Kong, China.,Laboratory of Data Discovery for Health, Hong Kong Science Park, Hong Kong, China.,Centre for PanorOmic Sciences (CPOS), The University of Hong Kong, Hong Kong, China
| | - Wai K Leung
- Department of Medicine, The University of Hong Kong, Hong Kong, China
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Kim S, Shin YC, Kim TY, Kim Y, Lee YS, Lee SH, Kim MN, O E, Kim KS, Kweon MN. Mucin degrader Akkermansia muciniphila accelerates intestinal stem cell-mediated epithelial development. Gut Microbes 2022; 13:1-20. [PMID: 33678130 PMCID: PMC7946046 DOI: 10.1080/19490976.2021.1892441] [Citation(s) in RCA: 165] [Impact Index Per Article: 55.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023] Open
Abstract
Mucin-degrading bacteria are densely populated in the intestinal epithelium; however, their interaction with intestinal stem cells (ISCs) and their progeny have not been elucidated. To determine whether mucin-degrading bacteria play a role in gut homeostasis, mice were treated with Akkermansia muciniphila, a specialized species that degrades mucin. Administration of A. muciniphila for 4 weeks accelerated the proliferation of Lgr5+ ISCs and promoted the differentiation of Paneth cells and goblet cells in the small intestine (SI). We found similar effects of A. muciniphila in the colon. The levels of acetic and propionic acids were higher in the cecal contents of A. muciniphila-treated mice than in PBS-treated mice. SI organoids treated with cecal contents obtained from A. muciniphila-treated mice were larger and could be diminished by treatment with G protein-coupled receptor (Gpr) 41/43 antagonists. Pre-treatment of mice with A. muciniphila reduced gut damage caused by radiation and methotrexate. Further, a novel isotype of the A. muciniphila strain was isolated from heathy human feces that showed enhanced function in intestinal epithelial regeneration. These findings suggest that mucin-degrading bacteria (e.g., A. muciniphila) may play a crucial role in promoting ISC-mediated epithelial development and contribute to intestinal homeostasis maintenance.
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Affiliation(s)
- Seungil Kim
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yun-Chan Shin
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Tae-Young Kim
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yeji Kim
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Yong-Soo Lee
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Su-Hyun Lee
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Mi-Na Kim
- Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Eunju O
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Kwang Soon Kim
- Department of Life Sciences, Pohang University of Science and Technology, Pohang, Republic of Korea
| | - Mi-Na Kweon
- Mucosal Immunology Laboratory, Department of Convergence Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea,CONTACT Mi-Na Kweon Department of Convergence Medicine, Asan Medical Center, Seoul, Republic of Korea
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Suzuki S, Gotoda T, Takano C, Horii T, Sugita T, Ogura K, Ichijima R, Kusano C, Ikehara H. Long term impact of vonoprazan-based Helicobacter pylori treatment on gut microbiota and its relation to post-treatment body weight changes. Helicobacter 2021; 26:e12851. [PMID: 34486195 DOI: 10.1111/hel.12851] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/17/2021] [Revised: 08/24/2021] [Accepted: 08/26/2021] [Indexed: 02/06/2023]
Abstract
BACKGROUND Vonoprazan-based Helicobacter pylori (H. pylori) treatment is highly effective in eradicating the target bacteria; however, its post-1-year impact on gut microbiota is unknown. This study evaluated the impact of vonoprazan-based H. pylori therapy on gut microbiota 1-year post-therapy and investigated the relationship between body weight changes and post-therapy gut microbiota perturbations. MATERIALS AND METHODS Between March and May 2019, 43 patients with H. pylori infections received either vonoprazan/amoxicillin (VA) or vonoprazan/amoxicillin/clarithromycin (VAC) therapy. Fecal samples were collected prior to treatment and 1 year after treatment. The alpha and beta diversities and the bacterial taxa composition ratios were determined using polymerase chain reaction amplification of the V3-V4 region of the 16S ribosomal RNA gene. The correlation between body weight changes and relative abundances of genera post-therapy was also analyzed. RESULTS Among the 43 patients, 18 received VA therapy and 21 received VAC therapy. One year after treatment, the alpha diversity was significantly higher in both the treatment groups (p < .001, using observed operational taxonomic units and Chao1 index), and beta diversity was significantly different in both the groups (p = .001, using unweighted UniFrac distance) compared with baseline findings. Significant positive correlations were found between body weight changes and the relative abundances of Coprococcus spp. (p = .037) and Odoribacter spp. (p = .022) post-therapy. CONCLUSION Vonoprazan-based H. pylori therapies are associated with long-term impacts on gut microbiota, including effects on bacterial species richness, and potentially affect metabolism by altering the microbiota. TRIAL REGISTRATION NUMBER UMIN000040025.
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Affiliation(s)
- Sho Suzuki
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
- Department of Gastroenterology, Yuri Kumiai General Hospital, Akita, Japan
| | - Takuji Gotoda
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Chika Takano
- Department of Pediatrics and Child Health, Nihon University School of Medicine, Tokyo, Japan
- Division of Microbiology, Department of Pathology and Microbiology, Nihon University School of Medicine, Tokyo, Japan
| | - Toshiki Horii
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Tomomi Sugita
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Kanako Ogura
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Ryoji Ichijima
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
| | - Chika Kusano
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Hisatomo Ikehara
- Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan
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Van Zyl KN, Matukane SR, Hamman BL, Whitelaw AC, Newton-Foot M. The effect of antibiotics on the human microbiome: a systematic review. Int J Antimicrob Agents 2021; 59:106502. [DOI: 10.1016/j.ijantimicag.2021.106502] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/03/2021] [Revised: 12/01/2021] [Accepted: 12/11/2021] [Indexed: 12/01/2022]
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Abstract
Little is known about the influence of gastric microbiota on host metabolism, even though the stomach plays an important role in the production of hormones involved in body weight regulation and glucose homeostasis. Proton pump inhibitors (PPIs) and Helicobacter pylori alter gut microbiota, but their impact on gastric microbiota in patients with obesity and the influence of these factors on the metabolic response to bariatric surgery is not fully understood. Forty-one subjects with morbid obesity who underwent sleeve gastrectomy were included in this study. The H. pylori group was established by the detection of H. pylori using a sequencing-based method (n = 16). Individuals in whom H. pylori was not detected were classified according to PPI treatment. Gastric biopsy specimens were obtained during surgery and were analyzed by a high-throughput-sequencing method. Patients were evaluated at baseline and 3, 6, and 12 months after surgery. β-Diversity measures were able to cluster patients according to their gastric mucosa-associated microbiota composition. H. pylori and PPI treatment are presented as two important factors for gastric mucosa-associated microbiota. H. pylori reduced diversity, while PPIs altered β-diversity. Both factors induced changes in the gastric mucosa-associated microbiota composition and its predicted functions. PPI users showed lower percentages of change in the body mass index (BMI) in the short term after surgery, while the H. pylori group showed higher glucose levels and lower percentages of reduction in body weight/BMI 1 year after surgery. PPIs and H. pylori colonization could modify the gastric mucosa-associated microbiota, altering its diversity, composition, and predicted functionality. These factors may have a role in the metabolic evolution of patients undergoing bariatric surgery. IMPORTANCE The gut microbiota has been shown to have an impact on host metabolism. In the stomach, factors like proton pump inhibitor treatment and Helicobacter pylori haven been suggested to alter gut microbiota; however, the influence of these factors on the metabolic response to bariatric surgery has not been fully studied. In this study, we highlight the impact of these factors on the gastric microbiota composition. Moreover, proton pump inhibitor treatment and the presence of Helicobacter pylori could have an influence on bariatric surgery outcomes, mainly on body weight loss and glucose homeostasis. Deciphering the relationship between gastric hormones and gastric microbiota and their contributions to bariatric surgery outcomes paves the way to develop gut manipulation strategies to improve the metabolic success of bariatric surgery.
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Iino C, Shimoyama T. Impact of Helicobacter pylori infection on gut microbiota. World J Gastroenterol 2021; 27:6224-6230. [PMID: 34712028 PMCID: PMC8515792 DOI: 10.3748/wjg.v27.i37.6224] [Citation(s) in RCA: 30] [Impact Index Per Article: 7.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Revised: 05/13/2021] [Accepted: 09/02/2021] [Indexed: 02/06/2023] Open
Abstract
A number of studies have revealed the association between Helicobacter pylori (H. pylori) infection and the gut microbiota. More than half of the investigations on the impact of H. pylori on the gut microbiota have been the sub-analyses of the influence of eradication therapy. It was observed that H. pylori eradication altered gut microbiota within a short period after eradication, and majority of the alterations took a long period of time to reverse back to the original. Changes in the gut microbiota within a short period after eradication may be attributed to antibiotics and proton pump inhibitors. Modification of gastric acidity in the stomach caused by a long-term H. pylori infection alters the gut microbiota. Analysis of the gut microbiota should be conducted in a large population, adjusting for considerable biases associated with the composition of the gut microbiota, such as age, sex, body mass index, diet and the virulence of H. pylori.
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Affiliation(s)
- Chikara Iino
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
| | - Tadashi Shimoyama
- Department of Gastroenterology, Hirosaki University Graduate School of Medicine, Hirosaki 036-8562, Japan
- Department of Internal Medicine, Aomori General Health Examination Center, Aomori 030-0962, Japan
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Jo HG, Kim YS. Helicobacter pylori Eradication Therapy-associated Diarrhea. THE KOREAN JOURNAL OF HELICOBACTER AND UPPER GASTROINTESTINAL RESEARCH 2021. [DOI: 10.7704/kjhugr.2021.0037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Eradication of Helicobacter pylori has contributed to the treatment of peptic ulcers and mucosa-associated lymphoid tissue lymphoma. Moreover, it has possibly decreased the prevalence of gastric cancer. However, eradication therapy is associated with various adverse effects, of which diarrhea is the most common. The incidence of diarrhea after eradication treatment varies from 8% to 48%. In particular, the incidence is higher in patients who receive first-line standard triple therapy compared with those who receive second-line therapy. Both antibiotics and proton pump inhibitors, components of eradication therapy, have short-term and long-term impacts on gut microbiota. The alterations of gut microbiota may not recover until 1 year after eradication therapy. Most cases of diarrhea that occur after eradication therapy are antibiotic-associated diarrhea caused by the destruction of the normal gut microbiota. In some cases, Clostridioides difficile-associated diarrhea occurs after eradication therapy. If bloody diarrhea occurs after eradication therapy and the Clostridioides difficile toxin is not detected, antibiotic-associated hemorrhagic colitis associated with Klebsiella oxytoca infection should be suspected. It is crucial to explain the possibility of diarrhea before initiating eradication therapy to increase compliance. Furthermore, probiotics may be administered to reduce diarrhea. If severe diarrhea or symptoms other than the usual antibiotic-associated diarrhea occur during or after eradication therapy, antibiotics should be discontinued. In addition, appropriate tests to determine the cause of diarrhea should be performed. This review summarizes the alteration of the gut microbiota, the causes of diarrhea after Helicobacter pylori eradication therapy, and its management.
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Martín-Núñez GM, Cornejo-Pareja I, Clemente-Postigo M, Tinahones FJ, Moreno-Indias I. Helicobacter pylori Eradication Therapy Affect the Gut Microbiota and Ghrelin Levels. Front Med (Lausanne) 2021; 8:712908. [PMID: 34458288 PMCID: PMC8387937 DOI: 10.3389/fmed.2021.712908] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/25/2021] [Accepted: 07/12/2021] [Indexed: 12/12/2022] Open
Abstract
Background: Antibiotic therapy used to eradicate Helicobacter pylori has been associated with changes in plasma ghrelin and alterations in the gut microbiota. On the other hand, changes in ghrelin levels have been related to changes in gut microbiota composition. Our aim was to evaluate the relationship between changes in the gut microbiota and ghrelin levels in H. pylori infected patients who received antibiotic treatment for its eradication. Methods: A prospective case-control study that included forty H. pylori-positive patients who received eradication therapy (omeprazole, clarithromycin, and amoxicillin) and twenty healthy H. pylori antigen-negative participants. Patients were evaluated, including clinical, anthropometric and dietary variables, before and 2 months after treatment. Gut microbiota composition was analyzed through 16S rRNA amplicon sequencing (IlluminaMiSeq). Results: Changes in gut microbiota profiles and decrease in ghrelin levels were identified after H. pylori eradication treatment. Gut bacteria such as Bifidobacterium longum, Bacteroides, Prevotella, Parabacteroides distasonis, and RS045 have been linked to ghrelin levels fasting and/or post meals. Changes in the abundance of Lachnospiraceae, its genus Blautia, as well as Prevotella stercorea, and Megasphaera have been inversely associated with changes in ghrelin after eradication treatment. Conclusions: Eradication treatment for H. pylori produces changes in the composition of the intestinal microbiota and ghrelin levels. The imbalance between lactate producers such as Blautia, and lactate consumers such as Megasphaera, Lachnospiraceae, or Prevotella, could trigger changes related to ghrelin levels under the alteration of the eradication therapy used for H. pylori. In addition, acetate producing bacteria such as B. longum, Bacteroides, and P. distasonis could also play an important role in ghrelin regulation.
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Affiliation(s)
- Gracia Mª Martín-Núñez
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Cornejo-Pareja
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Mercedes Clemente-Postigo
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.,Department of Cell Biology, Physiology, and Immunology, Maimónides Biomedical Research Institute of Córdoba (IMIBIC)/University of Córdoba/Reina Sofia University Hospital, Córdoba, Spain
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Moreno-Indias
- Department of Endocrinology and Nutrition, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
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Merenstein D, Fraser CM, Roberts RF, Liu T, Grant-Beurmann S, Tan TP, Smith KH, Cronin T, Martin OA, Sanders ME, Lucan SC, Kane MA. Bifidobacterium animalis subsp. lactis BB-12 Protects against Antibiotic-Induced Functional and Compositional Changes in Human Fecal Microbiome. Nutrients 2021; 13:nu13082814. [PMID: 34444974 PMCID: PMC8398419 DOI: 10.3390/nu13082814] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/27/2021] [Accepted: 08/11/2021] [Indexed: 01/04/2023] Open
Abstract
The administration of broad-spectrum antibiotics is often associated with antibiotic-associated diarrhea (AAD), and impacts gastrointestinal tract homeostasis, as evidenced by the following: (a) an overall reduction in both the numbers and diversity of the gut microbiota, and (b) decreased short-chain fatty acid (SCFA) production. Evidence in humans that probiotics may enhance the recovery of microbiota populations after antibiotic treatment is equivocal, and few studies have addressed if probiotics improve the recovery of microbial metabolic function. Our aim was to determine if Bifidobacterium animalis subsp. lactis BB-12 (BB-12)-containing yogurt could protect against antibiotic-induced fecal SCFA and microbiota composition disruptions. We conducted a randomized, allocation-concealed, controlled trial of amoxicillin/clavulanate administration (days 1-7), in conjunction with either BB-12-containing or control yogurt (days 1-14). We measured the fecal levels of SCFAs and bacterial composition at baseline and days 7, 14, 21, and 30. Forty-two participants were randomly assigned to the BB-12 group, and 20 participants to the control group. Antibiotic treatment suppressed the fecal acetate levels in both the control and probiotic groups. Following the cessation of antibiotics, the fecal acetate levels in the probiotic group increased over the remainder of the study and returned to the baseline levels on day 30 (-1.6% baseline), whereas, in the control group, the acetate levels remained suppressed. Further, antibiotic treatment reduced the Shannon diversity of the gut microbiota, for all the study participants at day 7. The magnitude of this change was larger and more sustained in the control group compared to the probiotic group, which is consistent with the hypothesis that BB-12 enhanced microbiota recovery. There were no significant baseline clinical differences between the two groups. Concurrent administration of amoxicillin/clavulanate and BB-12 yogurt, to healthy subjects, was associated with a significantly smaller decrease in the fecal SCFA levels and a more stable taxonomic profile of the microbiota over time than the control group.
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Affiliation(s)
- Daniel Merenstein
- Department of Family Medicine, Georgetown University Medical Center, Washington, DC 20057, USA; (T.P.T.); (K.H.S.); (T.C.)
- Department of Human Science, School of Nursing and Health Studies, Georgetown University Medical Center, Washington, DC 20057, USA
- Correspondence: (D.M.); (C.M.F.); (M.A.K.); Tel.: +1-202-687-2745 (D.M.); +1-410-706-3879 (C.M.F.); +1-410-706-5097 (M.A.K.)
| | - Claire M. Fraser
- Institute for Genomic Sciences, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.G.-B.); (O.A.M.)
- Correspondence: (D.M.); (C.M.F.); (M.A.K.); Tel.: +1-202-687-2745 (D.M.); +1-410-706-3879 (C.M.F.); +1-410-706-5097 (M.A.K.)
| | - Robert F. Roberts
- Department of Food Science, The Pennsylvania State University, University Park, PA 16802, USA;
| | - Tian Liu
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA;
| | - Silvia Grant-Beurmann
- Institute for Genomic Sciences, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.G.-B.); (O.A.M.)
| | - Tina P. Tan
- Department of Family Medicine, Georgetown University Medical Center, Washington, DC 20057, USA; (T.P.T.); (K.H.S.); (T.C.)
| | - Keisha Herbin Smith
- Department of Family Medicine, Georgetown University Medical Center, Washington, DC 20057, USA; (T.P.T.); (K.H.S.); (T.C.)
| | - Tom Cronin
- Department of Family Medicine, Georgetown University Medical Center, Washington, DC 20057, USA; (T.P.T.); (K.H.S.); (T.C.)
| | - Olivia A. Martin
- Institute for Genomic Sciences, Departments of Medicine and Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD 21201, USA; (S.G.-B.); (O.A.M.)
- Department of Surgery, University of Maryland School of Medicine, Baltimore, MD 21201, USA
| | | | - Sean C. Lucan
- Department of Family and Social Medicine, Albert Einstein College of Medicine, Montefiore Health System, Bronx, NY 10461, USA;
| | - Maureen A. Kane
- Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore, MD 21201, USA;
- Correspondence: (D.M.); (C.M.F.); (M.A.K.); Tel.: +1-202-687-2745 (D.M.); +1-410-706-3879 (C.M.F.); +1-410-706-5097 (M.A.K.)
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Zhou Y, Ye Z, Wang Y, Huang Z, Zheng C, Shi J, Tang W, Zhang P, Wang S, Huang Y. Long-term changes in the gut microbiota after triple therapy, sequential therapy, bismuth quadruple therapy and concomitant therapy for Helicobacter pylori eradication in Chinese children. Helicobacter 2021; 26:e12809. [PMID: 33899288 DOI: 10.1111/hel.12809] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 03/29/2021] [Accepted: 04/01/2021] [Indexed: 12/18/2022]
Abstract
BACKGROUND We previously reported that the administration of 14-day standard triple therapy (TT), sequential therapy (ST), bismuth-based quadruple therapy (BT), and concomitant therapy (CT) as the first-line therapy for Helicobacter pylori infection in Chinese children achieved eradication rates of 74.1%, 69.5%, 89.8%, and 84.6%, respectively. In this follow-up study, we further evaluated the short- and long-term effects of the four regimens on the gut microbiota in these children. METHODS We prospectively recruited treatment-naïve children with H. pylori infection. Fecal samples were collected at week 0, 2, 6, and 52, and alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS Sixty-three patients participated in this study (16 with TT, 15 with ST, 16 with BT and 16 with CT). At week 2, the alpha diversity (Shannon and Chao 1 index) was significantly reduced in the TT (p = 0.008, p < 0.001), ST (p < 0.001, p < 0.001), BT (p < 0.001, p < 0.001) and CT groups (p < 0.001, p < 0.001). Some changes persisted in the ST, BT, and CT groups at week 6, and all were restored (expect p = 0.02 with Chao 1 index in the CT group) at week 52. The beta diversity was significantly changed in the BT (p = 0.001) and CT groups (p = 0.001) 2 weeks post-eradication and restored 1 year after therapy. Immediately after therapy, the relative abundance of Proteobacteria was strikingly increased in the ST (p = 0.005), BT (p < 0.001) and CT groups (p < 0.001), and the genus-level analysis showed that the abundances of 23.1%, 43.3%, 78.6%, and 78% of the bacterial genera in the TT, ST, BT, and CT groups were significantly changed. All these changes returned to almost the pre-eradication level 1 year post-eradication. CONCLUSION Eradication of H. pylori infection can lead to transient dysbiosis of gut microbiota, and these changes almost recovered 1 year post-eradication, which indicates the long-term safety of H. pylori therapy.
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Affiliation(s)
- Ying Zhou
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Ziqing Ye
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Zhiheng Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Cuifang Zheng
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Jieru Shi
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Wenjuan Tang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Ping Zhang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Shengnan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China
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Martin-Nuñez GM, Cornejo-Pareja I, Clemente-Postigo M, Tinahones FJ. Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders? Front Endocrinol (Lausanne) 2021; 12:639856. [PMID: 34220702 PMCID: PMC8247771 DOI: 10.3389/fendo.2021.639856] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/10/2020] [Accepted: 05/17/2021] [Indexed: 12/14/2022] Open
Abstract
Helicobacter pylori (H. pylori) is a gram-negative bacterium that infects approximately 4.4 billion individuals worldwide. Although the majority of infected individuals remain asymptomatic, this bacterium colonizes the gastric mucosa causing the development of various clinical conditions as peptic ulcers, chronic gastritis and gastric adenocarcinomas and mucosa-associated lymphoid tissue lymphomas, but complications are not limited to gastric ones. Extradigestive pathologies, including metabolic disturbances such as diabetes, obesity and nonalcoholic fatty liver disease, have also been associated with H. pylori infection. However, the underlying mechanisms connecting H. pylori with extragastric metabolic diseases needs to be clarified. Notably, the latest studies on the topic have confirmed that H. pylori infection modulates gut microbiota in humans. Damage in the gut bacterial community (dysbiosis) has been widely related to metabolic dysregulation by affecting adiposity, host energy balance, carbohydrate metabolism, and hormonal modulation, among others. Taking into account that Type 2 diabetic patients are more prone to be H. pylori positive, gut microbiota emerges as putative key factor responsible for this interaction. In this regard, the therapy of choice for H. pylori eradication, based on proton pump inhibitor combined with two or more antibiotics, also alters gut microbiota composition, but consequences on metabolic health of the patients has been scarcely explored. Recent studies from our group showed that, despite decreasing gut bacterial diversity, conventional H. pylori eradication therapy is related to positive changes in glucose and lipid profiles. The mechanistic insights explaining these effects should also be addressed in future research. This review will deal with the role of gut microbiota as the linking factor between H. pylori infection and metabolic diseases, and discussed the impact that gut bacterial modulation by H. pylori eradication treatment can also have in host's metabolism. For this purpose, new evidence from the latest human studies published in more recent years will be analyzed.
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Affiliation(s)
- Gracia M. Martin-Nuñez
- Unidad de Gestión Clínica de Endocrinología y Nutrición (Hospital Universitario Virgen de la Victoria), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Isabel Cornejo-Pareja
- Unidad de Gestión Clínica de Endocrinología y Nutrición (Hospital Universitario Virgen de la Victoria), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
| | - Mercedes Clemente-Postigo
- Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- Department of Cell Biology, Physiology and Immunology. Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC)-Reina Sofia University Hospital, University of Cordoba, Córdoba, Spain
- *Correspondence: Francisco J. Tinahones, ; Mercedes Clemente-Postigo,
| | - Francisco J. Tinahones
- Unidad de Gestión Clínica de Endocrinología y Nutrición (Hospital Universitario Virgen de la Victoria), Instituto de Investigación Biomédica de Málaga (IBIMA), Universidad de Málaga, Málaga, Spain
- Centro de Investigación Biomédica en Red (CIBER) Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III (ISCIII), Madrid, Spain
- *Correspondence: Francisco J. Tinahones, ; Mercedes Clemente-Postigo,
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Chen CC, Liou JM, Lee YC, Hong TC, El-Omar EM, Wu MS. The interplay between Helicobacter pylori and gastrointestinal microbiota. Gut Microbes 2021; 13:1-22. [PMID: 33938378 PMCID: PMC8096336 DOI: 10.1080/19490976.2021.1909459] [Citation(s) in RCA: 104] [Impact Index Per Article: 26.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2020] [Revised: 03/10/2021] [Accepted: 03/19/2021] [Indexed: 02/07/2023] Open
Abstract
The complex population of microbes in the human gastrointestinal (GI) tract interacts with itself and with the host, exerting a deep influence on health and disease development. The development of modern sequencing technology has enabled us to gain insight into GI microbes. Helicobacter pylori colonization significantly affects the gastric microenvironment, which in turn affects gastric microbiota and may be correlated with colonic microbiota changes. Crosstalk between H. pylori and GI commensal flora may play a role in H. pylori-related carcinogenicity and extragastric manifestations. We review current knowledge on how H. pylori shapes GI microbiota with a specific focus on its impact on the stomach and colon. We also review current evidence on colonic microbiota changes attributed to eradication therapy based on the clinical studies performed to date.
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Affiliation(s)
- Chieh-Chang Chen
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medicine, National Taiwan University Cancer Center, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Yi-Chia Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
- Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Tzu-Chan Hong
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Emad M El-Omar
- Microbiome Research Centre, St George & Sutherland Clinical School, University of New South Wales, Sydney, NSW, Australia
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Department of Internal Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
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Tao ZH, Han JX, Fang JY. Helicobacter pylori infection and eradication: Exploring their impacts on the gastrointestinal microbiota. Helicobacter 2020; 25:e12754. [PMID: 32876377 DOI: 10.1111/hel.12754] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 07/12/2020] [Accepted: 08/03/2020] [Indexed: 12/16/2022]
Abstract
The rapid development of microbiota research has remolded our view of human physiological and pathological processes. Among all the gastrointestinal microorganisms, Helicobacter pylori (H pylori) is probably the most notorious constituent. Although half of the adults worldwide are infected with H pylori, their clinical manifestations vary widely, suggesting other microorganisms beyond H pylori may play a role in determining clinical outcomes. Recently, many studies have put effort into elucidating the crosstalk within the human microbiota, some of which specifically explored the interplay between H pylori and other gastrointestinal microbial members. In this work, we reviewed these potential interactions. Meanwhile, the impacts of H pylori eradication therapy on gastrointestinal microbial homeostasis were summarized in terms of diversity, composition, functional capacity, and antibiotic resistance.
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Affiliation(s)
- Zhi-Hang Tao
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Ji-Xuan Han
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
| | - Jing-Yuan Fang
- State Key Laboratory for Oncogenes and Related Genes, Key Laboratory of Gastroenterology and Hepatology, Division of Gastroenterology and Hepatology, Shanghai Institute of Digestive Disease, Ministry of Health, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
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Zhou Y, Ye Z, Lu J, Miao S, Lu X, Sun H, Wu J, Wang Y, Huang Y. Long-term changes in the gut microbiota after 14-day bismuth quadruple therapy in penicillin-allergic children. Helicobacter 2020; 25:e12721. [PMID: 32656891 DOI: 10.1111/hel.12721] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 06/09/2020] [Accepted: 06/16/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND Penicillin-allergic children who are infected with Helicobacter pylori constitute a relatively common subgroup. We aimed to study the short-term and long-term effects of bismuth quadruple therapy on gut microbiota in penicillin-allergic children. METHODS We prospectively recruited treatment-naive children with H pylori infection and H pylori-negative asymptomatic children as healthy controls. Patients received 14-day bismuth quadruple therapy consisting of omeprazole, clarithromycin, metronidazole, and bismuth. Fecal samples were collected at weeks 0, 2, 6, and 52. Alterations in the gut microbiota were analyzed by 16S rRNA gene sequencing. RESULTS Twenty-two subjects (14 gastritis patients, 8 duodenal ulcer patients) and 23 controls participated in this study. At week 2, alpha diversity was reduced in both gastritis (P < .05) and ulcer (except P = .16 with Chao 1 index) patients compared with baseline. Some changes persisted at week 6, and all were restored at week 52. Beta diversity was significantly altered 2 weeks after treatment in the gastritis and duodenal ulcer groups (P = .001, P = .002, respectively) and restored at weeks 6 and 52. The mean relative abundance of Bacteroidetes (P < .001, P = .005, respectively) decreased and that of Proteobacteria increased (P < .001, P = .03, respectively). All alterations recovered at week 6 and 52. In both the gastritis and ulcer groups at week 2, some beneficial bacteria were decreased including Bacteroides (P < .001 and P = .003), Faecalibacterium (P < .001 and P = .02), Phascolarctobacterium (P = .002 and P = .004), Roseburia ( P < .001 and P = .13), Bifidobacterium (P = .08 and P = .04), and Blautia (P < .001 and P = .002). Some detrimental bacteria were increased including Escherichia-Shigella (P < .001 and P = .19), Klebsiella (P < .001, and P = .09), Enterococcus (P < .001 and P = .007), and Streptococcus (P = .002 and P = .004). The changes returned to almost the pre-eradication level 1 year after therapy. CONCLUSION Bismuth quadruple therapy causes short-term dysbiosis of the gut microbiota. Most changes recovered 1-year post-eradication, indicating the long-term safety of H pylori therapy.
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Affiliation(s)
- Ying Zhou
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ziqing Ye
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Junping Lu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Shijian Miao
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Xiaolan Lu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Hua Sun
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Jie Wu
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Yuhuan Wang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
| | - Ying Huang
- Department of Gastroenterology, Children's Hospital of Fudan University, Shanghai, China
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Gudra D, Pupola D, Skenders G, Leja M, Radovica-Spalvina I, Gorskis H, Vangravs R, Fridmanis D. Lack of significant differences between gastrointestinal tract microbial population structure of Helicobacter pylori-infected subjects before and 2 years after a single eradication event. Helicobacter 2020; 25:e12748. [PMID: 32776403 DOI: 10.1111/hel.12748] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2020] [Revised: 07/13/2020] [Accepted: 07/14/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND According to recent estimates 80% of Latvian population is infected with Helicobacter pylori thus their susceptibility to numerous gastric tract diseases is increased. The 1st line H. pylori eradication therapy includes treatment with clarithromycin in combination with amoxicillin or metronidazole and a proton pump inhibitor. However, potential adverse events caused by such therapies to microbiome are insufficiently studied. OBJECTIVE This study aimed to evaluate the long-term effect of H. pylori eradication on human gastrointestinal tract (GIT) microbiome. METHODS The assessment of H pylori eradication impact on GIT microbiome was done by analyzing 120 samples acquired from 60 subjects. Each individual was prescribed the following 10-day eradication regimen: Esomeprazolum 40 mg, Clarithromycinum 500 mg, and Amoxicillinum 1000 mg, BID. Samples from each individual were collected before starting H pylori eradication therapy, and 2 years after the completion of the therapy in OC-Sensor (Eiken Chemical Co.) sample collection containers and stored at -86°C. Prior to DNA extraction, the samples were lyophilized, and total DNA was extracted using FastDNA Spin Kit for Soil. 16S V3 rRNA gene sequencing was done employing Ion Torrent PGM, and the obtained raw sequences were analyzed using vsearch and R (phyloseq, cluster packages). RESULTS Alpha diversity measurements-observed OTUs, Chao1 and Shannon index did not differ significantly between the pre- and post-eradication states (two-tailed paired t test: P = .95; P = .71, P = .24, respectively). Unweighted and weighted UniFrac distances of beta diversity analysis indicated a non-specific pattern of sample clustering. Enterotype shift was observed for the majority of individuals comparing pre- and post-eradication study groups. Association analysis revealed that certain bacterial genera significantly correlated with age (eg, Dialister, Paraprevotella, Bifidobacterium), individual (eg, Thermotunica, Streptomyces, Faecalibacterium), and history of respiratory and/or allergic diseases (eg, Colinsella, Faecalibacterium). Redundancy analysis confirmed that the individual was a significant determinant of the subject's microbial community composition (ANOVA, 999 perm., P = .001) with the further lower impact of subject-specific medical history (eg, medication used as prescribed: P = .005, history of cardiovascular diseases: P = .005, history of respiratory, and/or allergic diseases: P = .015) and physiological (eg, age: P = .005, gender: P = .02) parameters. In the post-eradication study group, number of influential genera (n = 260) was increased compared to the pre-eradication study group (n = 209). CONCLUSION Modest global differences at the community level exist between individuals before and after the eradication therapy; however, the microbiome structure is more related to the subject-specific parameters rather than by the eradication therapy itself.
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Affiliation(s)
- Dita Gudra
- Latvian Biomedical Research and Study Centre, Riga, Latvia
| | - Darta Pupola
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Girts Skenders
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Marcis Leja
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia.,Faculty of Medicine, University of Latvia, Riga, Latvia
| | | | - Henrihs Gorskis
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Reinis Vangravs
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
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Martín-Núñez GM, Cornejo-Pareja I, Roca-Rodríguez MDM, Clemente-Postigo M, Cardona F, Fernández-García JC, Moreno-Indias I, Tinahones FJ. H. pylori Eradication Treatment Causes Alterations in the Gut Microbiota and Blood Lipid Levels. Front Med (Lausanne) 2020; 7:417. [PMID: 32850910 PMCID: PMC7431686 DOI: 10.3389/fmed.2020.00417] [Citation(s) in RCA: 16] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2020] [Accepted: 06/30/2020] [Indexed: 12/12/2022] Open
Abstract
Background: The gut microbiome plays an important role in the lipid metabolism. Antibiotic treatment causes changes in the intestinal microbiota. Our objective was to explore the relationship between changes in the intestinal microbiota and the level of plasma high density lipoprotein cholesterol (HDL) and low density lipoprotein cholesterol (LDL). Methods: Prospective case-control study with Helicobacter pylori-positive patients undergoing eradication therapy with omeprazole, clarithromycin, and amoxicillin. Stool and blood samples were obtained from 20 controls (H. pylori negative) and 40 patients before and 2 months after antibiotic treatment. Gut microbiota was determined through 16S rRNA amplicon sequencing (Illumina MiSeq). Results: Eradication treatment for H. pylori increased the HDL levels, and caused changes in gut microbiota profiles. An unfavorable lipid profiles (high LDL and low HDL levels) was associated with a low microbial richness and an increase of the Bacteroidetes phylum. Prevotella copri, Lachonobacterium, and Delsufovibrio were positively associated with HDL while Rikenellaceae was negatively associated with HDL after completing antibiotic treatment. Conclusions:Helicobacter pylori eradication treatment could improve lipid metabolism in relation with an increase in the HDL. Changes in the abundance of specific bacteria, such as P. copri, Lachonobacterium, Delsufovibrio, and Rikenellaceae could be associated with change in the plasma HDL levels.
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Affiliation(s)
- Gracia M Martín-Núñez
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Cornejo-Pareja
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | | | - Mercedes Clemente-Postigo
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain.,Departamento de Biología Celular, Fisiología e Inmunología, Instituto Maimónides de Investigación Biomédica de Córdoba (IMIBIC), Universidad de Córdoba, Hospital Universitario Reina Sofía, Córdoba, Spain
| | - Fernando Cardona
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - José C Fernández-García
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Isabel Moreno-Indias
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
| | - Francisco J Tinahones
- Unidad de Endocrinología y Nutrición, Hospital Universitario Virgen de la Victoria, Málaga, Spain.,Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, Spain
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Ye Q, Shao X, Shen R, Chen D, Shen J. Changes in the human gut microbiota composition caused by Helicobacter pylori eradication therapy: A systematic review and meta-analysis. Helicobacter 2020; 25:e12713. [PMID: 32515529 DOI: 10.1111/hel.12713] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/11/2020] [Revised: 05/10/2020] [Accepted: 05/17/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND The short-term and long-term effect of Helicobacter pylori (H pylori) eradication on the gut microbiota is controversial; hence, this study aimed to clarify changes in the gut microbiome and microbial diversity after H pylori eradication. MATERIALS AND METHODS Articles published in PubMed, MEDLINE, and EMBASE were searched up to March 20, 2020, with English-language restriction. The outcomes including gut microbiota and alpha diversity were extracted to analysis. And then, Review Manager 5.3 software was used to conduct the data analysis. RESULTS At phylum level, next-generation sequencing was performed. Meta-analysis results showed that Actinobacteria decreased compared with baseline throughout the follow-up period. Proteobacteria increased during short-term follow-up and then returned to normal. In addition, Bacteroidetes decreased and Firmicutes increased only during long-term follow-up. At family or genus level, conventional microbiological culturing was performed. Enterobacteriaceae and Enterococcus both increased during the short-term and interim follow-up. In addition, Lactobacillus only showed a decreasing trend during short-term follow-up, but it appeared statistical decreasing during interim follow-up. Moreover, relatively sufficient evidence showed that alpha diversity decreased during short-term follow-up, and no reliable data were obtained to confirm the change of alpha diversity during interim and long-term follow-up. CONCLUSION In different follow-up periods after H pylori eradication, changes in gut microbiota were inconsistent. Microbial diversity decreased in the short-term follow-up, while there was no data to confirm subsequent alterations. The results provided a basis for the rational selection of probiotics in the eradication process. However, further studies are needed to obtain more clues.
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Affiliation(s)
- Qunqun Ye
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Xiaona Shao
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Ruiwei Shen
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Dawei Chen
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
| | - Jianwei Shen
- Department of Gastroenterology, Ningbo Medical Center Lihuili Hospital, Ningbo, China
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Liou JM, Lee YC, Wu MS. Treatment of Helicobacter pylori infection and its long-term impacts on gut microbiota. J Gastroenterol Hepatol 2020; 35:1107-1116. [PMID: 31984532 DOI: 10.1111/jgh.14992] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/05/2019] [Revised: 01/05/2020] [Accepted: 01/20/2020] [Indexed: 12/15/2022]
Abstract
The rising prevalence of antibiotic resistance and the long-term safety following eradication therapy are important issues in the management of Helicobacter pylori infection. The prevalence of clarithromycin, levofloxacin, and metronidazole resistance of H. pylori has increased to 21%, 27%, and 45%, respectively, in the Asia-Pacific region. Personalized treatment guided by susceptibility testing may provide a reliably excellent eradication rate in the first-line treatment but is costly and not widely available. Population-specific empirical therapy according to the local prevalence of antibiotic resistance may be an alternative strategy. Levofloxacin-based therapy and bismuth quadruple therapy are the recommended second-line rescue therapy. Susceptibility testing or genotypic resistance-guided therapy is the preferred treatment for refractory H. pylori infection, but empirical therapy may be an acceptable alternative. Eradication of H. pylori leads to short-term perturbation of gut microbiota. The diversity of gut microbiota can be restored months after eradication therapy, but the speed of recovery varies with regimens. The short-term increases of antibiotic resistance of Escherichia coli and Klebsiella pneumoniae may be restored to basal states months after H. pylori eradication. Future studies that apply in-depth sequencing, such as shotgun metagenomics sequencing, are needed to clarify whether the compositions of gut microbiota at the species level are fully restored.
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Affiliation(s)
- Jyh-Ming Liou
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan.,Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan
| | - Yi-Chia Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Ming-Shiang Wu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.,Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan
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46
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Gutiérrez-Repiso C, Moreno-Indias I, Martín-Núñez GM, Ho-Plágaro A, Rodríguez-Cañete A, Gonzalo M, García-Fuentes E, Tinahones FJ. Mucosa-associated microbiota in the jejunum of patients with morbid obesity: alterations in states of insulin resistance and metformin treatment. Surg Obes Relat Dis 2020; 16:1575-1585. [PMID: 32475753 DOI: 10.1016/j.soard.2020.04.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2019] [Revised: 03/26/2020] [Accepted: 04/04/2020] [Indexed: 12/13/2022]
Abstract
BACKGROUND Stool samples have been widely used to evaluate gut microbiota; however, little is known about the composition of human small intestinal microbiota and the alterations provoked by insulin resistance. OBJECTIVE To describe the composition of jejunal microbiota in morbidly obese patients, as well as its link with insulin resistance and metformin treatment. SETTING Virgen de la Victoria University Hospital and Regional University Hospital, Málaga, Spain. METHODS Jejunal biopsies from 46 morbidly obese patients were analyzed by next-generation sequencing method. Patients were classified in the following 3 groups: low homeostasis model assessment of insulin resistance index (HOMA-IR) value, high HOMA-IR value, and metformin-treated type 2 diabetes patients (T2D-metf). RESULTS Richness (q = .011) together with Proteobacteria (W = 2), Fusobacteria (W = 2), and Bacteroidetes (W = 1) phyla were significantly higher in high HOMA-IR compared with low HOMA-IR group. At family level, several differences were found between low HOMA-IR and T2D-metf group, being the most important the higher abundance of Halomonadacea in T2D-metf group (W = 22). PICRUSt analysis showed that predicted genes involved in trimethylamine-N-oxide biosynthesis pathway could be increased in jejunal microbiota of T2D-metf group compared with the low HOMA-IR group, while indole biosynthesis pathway could be increased in the low HOMA-IR group compared with the high HOMA-IR group. CONCLUSION An increase in richness and an enrichment in Proteobacteria, Fusobacteria, and Bacteroidetes was observed in jejunal from morbidly obese patients with high insulin resistance. Halomonadaceae family was significantly increased in metformin-treated patients. Functional analysis of predicted metagenome suggests that trimethylamine-N-oxide biosynthesis pathway could be increased in the jejunal microbiota of T2D-meft group, while indole biosynthesis pathway could be increased in low HOMA-IR group. These results contribute to the increase in the scarce knowledge about the mucosal microbiota of the hardly accessible small intestine.
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Affiliation(s)
- Carolina Gutiérrez-Repiso
- Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Madrid, Spain
| | - Isabel Moreno-Indias
- Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Madrid, Spain
| | - Gracia M Martín-Núñez
- Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Madrid, Spain
| | - Ailec Ho-Plágaro
- Unidad de Gestión Clínica de Aparato Digestivo del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain
| | - Alberto Rodríguez-Cañete
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Trasplantes, Hospital Regional Universitario de Málaga, Málaga, Spain; Departamento de Especialidades Quirúrgicas, Bioquímica e Inmunología, Universidad de Málaga, Málaga, Spain
| | - Monserrat Gonzalo
- Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Regional Universitario de Málaga, Instituto de Investigación Biomédica de Málaga, Málaga, Spain
| | - Eduardo García-Fuentes
- Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Madrid, Spain; Unidad de Gestión Clínica de Aparato Digestivo del Hospital Virgen de la Victoria. Instituto de Investigación Biomédica de Málaga, Málaga, Spain.
| | - Francisco J Tinahones
- Unidad de Gestión Clínica de Endocrinología y Nutrición del Hospital Virgen de la Victoria, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, Málaga, Spain; Centro de Investigación Biomédica en Red de Fisiopatología de la Obesidad y la Nutrición, CIBERobn, Madrid, Spain.
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47
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Cornejo-Pareja I, Martín-Núñez GM, Roca-Rodríguez MM, Cardona F, Coin-Aragüez L, Sánchez-Alcoholado L, Gutiérrez-Repiso C, Muñoz-Garach A, Fernández-García JC, Moreno-Indias I, Tinahones FJ. H. pylori Eradication Treatment Alters Gut Microbiota and GLP-1 Secretion in Humans. J Clin Med 2019; 8:jcm8040451. [PMID: 30987326 PMCID: PMC6517938 DOI: 10.3390/jcm8040451] [Citation(s) in RCA: 49] [Impact Index Per Article: 8.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/03/2019] [Revised: 03/26/2019] [Accepted: 03/30/2019] [Indexed: 02/07/2023] Open
Abstract
Changes in the intestinal microbial community and some metabolic disturbances, including obesity and type2 diabetes, are related. Glucagon-like peptide-1 (GLP-1) regulates glucose homeostasis. Microbiota have been linked to incretin secretion. Antibiotic use causes changes in microbial diversity and composition. Our aim was to evaluate the relationship between microbiota changes and GLP-1 secretion. A prospective case-control study with a Helicobacter pylori-positive patient model involving subjects under eradication therapy (omeprazole, clarithromycin, and amoxicillin). Forty patients with H. pylori infection and 20 matched participants, but negative for H. pylori antigen. Patients were evaluated before and two months after treatment. We analyzed anthropometric measurements, carbohydrate metabolism, lipid profile, and C-reactive protein. Gut microbiota composition was analyzed through 16S rRNA amplicon sequencing (IlluminaMiSeq). Eradication treatment for H. pylori decreased bacterial richness (Chao1, p = 0.041). Changes in gut microbiota profiles were observed at phylum, family, genus and species levels. GLP-1 secretion and variables of carbohydrate metabolism were improved. Correlations were seen between GLP-1 changes and variations within microbial community abundances, specifically Bifidobacterium adolescentis, the Lachnobacterium genus, and Coriobacteriaceae family. A conventional treatment to eradicate H. pylori could improve carbohydrate metabolism possibly in relation with an increase in GLP-1 secretion. GLP-1 secretion may be related to alterations in intestinal microbiota, specifically Lachnobacterium, B. adolescentis and Coriobacteriaceae.
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Affiliation(s)
- Isabel Cornejo-Pareja
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Gracia M Martín-Núñez
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
| | - M Mar Roca-Rodríguez
- Department of Endocrinology and Nutrition, Puerta del Mar University Hospital, 11009 Cadiz, Spain.
| | - Fernando Cardona
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Leticia Coin-Aragüez
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Lidia Sánchez-Alcoholado
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
| | - Carolina Gutiérrez-Repiso
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
| | - Araceli Muñoz-Garach
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - José C Fernández-García
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Isabel Moreno-Indias
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
| | - Francisco J Tinahones
- Department of Endocrinology and Nutrition, Virgen de la Victoria Hospital (IBIMA), Malaga University, 29010 Malaga, Spain.
- Centro de Investigacion Biomédica en Red de la Fisiopatología de la Obesidad y Nutrición (CIBEROBN CB06/003), Instituto de Salud Carlos III, 28029 Madrid, Spain.
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