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Wilson TM. Lung Microbiome in Autoimmune-Associated Interstitial Lung Disease. Rheum Dis Clin North Am 2025; 51:201-212. [PMID: 40246438 DOI: 10.1016/j.rdc.2025.01.003] [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] [Indexed: 04/19/2025]
Abstract
The lung microbiome is a diverse mucosal environment that has been shown to be implicated in the pathogenesis of various chronic lung diseases including insterstitial lung diseases (ILD) such as idiopathic pulmonary fibrosis (IPF). ILD is a well-established manifestation of several types of autoimmune diseases. This review will highlight recent work exploring the role of the lung microbiome in the pathogenesis of autoimmune-related ILD.
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Affiliation(s)
- Timothy M Wilson
- Division of Rheumatology, Thomas Jefferson University, 211 South 9th Street, Suite 210, Philadelphia, PA 19107, USA.
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2
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Brusselaers N, Khodir Kamal H, Graham D, Engstrand L. Proton pump inhibitors and the risk of gastric cancer: a systematic review, evidence synthesis and life course epidemiology perspective. BMJ Open Gastroenterol 2025; 12:e001719. [PMID: 40253055 PMCID: PMC12010335 DOI: 10.1136/bmjgast-2024-001719] [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: 12/20/2024] [Accepted: 04/09/2025] [Indexed: 04/21/2025] Open
Abstract
OBJECTIVES Since proton pump inhibitors (PPI) have been introduced, many concerns were raised regarding potential gastric carcinogenicity. We aim to summarise and weigh the epidemiological evidence and address possible causality. DESIGN Systematic literature review, evidence synthesis and life-course assessment. DATA SOURCES PubMed, Web of Science and Cochrane database (from inception up to October 2024), and back- and forward citation tracking (Web of Science). ELIGIBILITY CRITERIA Original studies and quantitative evidence syntheses assessing the association between PPIs and gastric cancer in humans, without language restrictions. DATA EXTRACTION AND SYNTHESIS Study design, definitions (and participant numbers) of PPI use and gastric cancer, study characteristics (setting, period, follow-up, lag-time), age and sex distribution presented in tables and evidence mapping. RESULTS We identified 33 original studies, 21 meta-analyses, three umbrella meta-analyses, one individual patient data meta-analysis and a Markov model (2006-2023). PPIs were consistently associated with an increased gastric cancer risk with 20/21 meta-analyses reporting pooled relative risks between 1.3 and 2.9. Available trials were underpowered. Reverse causation/protopathic bias, residual confounding (by indication) and lag time seem the largest methodological challenges, as well as disentangling the effects of Helicobacter pylori and its' eradication. Insufficient data are available on age and sex-specific risks, with no studies specifically addressing PPIs in young populations. We hypothesise a sensitive-period exposure model, in which PPI use during pregnancy and early life may be particularly damaging regarding long-term cancer risk. An exploration of Swedish cancer incidence data suggests potential cohort effects as overall gastric cancer risk decreased over time (1970-2022). The risk has increased in young (<40 years) men since the early 2000s, ~10 years after the introduction of Helicobacter pylori eradication and PPIs. CONCLUSION Although for older individuals with valid indications, the gastric cancer risk related to PPI use may be limited, we do argue for a more rational and evidence-supported use of PPIs in young populations.
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Affiliation(s)
- Nele Brusselaers
- Dept. of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
- Department of Family Medicine and Population Health, University of Antwerp, Antwerpen, Belgium
| | | | | | - Lars Engstrand
- Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, stockholm, Sweden
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3
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Shibano M, Takahashi M, Nakatsukasa H, Ishigami Y, Toyokawa T, Taira K, Kawaguchi T, Nakamura Y, Kaneda H. Proton pump inhibitors reduce nivolumab efficacy in unresectable advanced or recurrent gastric cancer. Immunotherapy 2025; 17:331-338. [PMID: 40228034 PMCID: PMC12045562 DOI: 10.1080/1750743x.2025.2491300] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2025] [Accepted: 04/07/2025] [Indexed: 04/16/2025] Open
Abstract
BACKGROUND Proton pump inhibitors (PPI) have been shown to decrease the efficacy of immune checkpoint inhibitors in patients with various cancer types. However, there are few reports on their effect on patients with gastric cancer (GC). Therefore, we investigated the efficacy of nivolumab in patients with GC receiving PPI. METHODS This retrospective study analyzed data of patients who received nivolumab monotherapy for unresectable advanced or recurrent GC at Osaka Metropolitan University Hospital between September 2017 and December 2021. The primary and secondary endpoints were progression-free survival (PFS) and overall survival (OS), respectively. PPI use was defined as within 30 days before and after initiation of nivolumab monotherapy. RESULTS Seventy-seven eligible patients were included in this analysis. PPIs were used in 33 patients, while 36 patients had a previous gastrectomy. Multivariate analysis revealed that only PPI use was an independent predictor of PFS (hazard ratio [HR] 1.93, 95% confidence interval [CI] 1.03-3.64, p = 0.042). Contrastingly, PPI use was not an independent predictor of OS. CONCLUSION PPIs may reduce the efficacy of nivolumab, and their use should be carefully considered in patients receiving nivolumab.
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Affiliation(s)
- Masahito Shibano
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Masaya Takahashi
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
- Department of Quality and Safety Management, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Hitomi Nakatsukasa
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Yusuke Ishigami
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Takahiro Toyokawa
- Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Koichi Taira
- Department of Gastroenterology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Tomoya Kawaguchi
- Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
| | - Yasutaka Nakamura
- Department of Pharmacy, Osaka Metropolitan University Hospital, Osaka, Japan
| | - Hiroyasu Kaneda
- Department of Clinical Oncology, Graduate School of Medicine, Osaka Metropolitan University, Osaka, Japan
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4
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Lemmens AS, Huysentruyt K, Vandenplas Y. Why think twice before prescribing proton pump inhibitors. Eur J Pediatr 2025; 184:227. [PMID: 40042553 DOI: 10.1007/s00431-025-06058-z] [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: 12/28/2024] [Revised: 02/20/2025] [Accepted: 02/24/2025] [Indexed: 03/26/2025]
Abstract
Proton pump inhibitors (PPIs) represent a class of drugs most prominently known for their use in acid-related disorders. Omeprazole, a drug belonging to this class, is among the top 10 most prescribed drugs in the USA. PPIs have a direct effect on the gastric pH and therefore on the gastric mucosa. This review aims to present the most common adverse effects PPIs have on the gastric mucosa in particular. CONCLUSION PPIs affect the composition of gut and gastric microbiota and will eventually modulate the immune response. WHAT IS KNOWN • Proton-pump inhibitors are amonth the most frequent prescirbed drugs becasue of their well demonstrated efficacy in acid-related disorders. • Because of their mode of action and their metabolism, a large spectrum of adversee effects have been reported. WHAT IS NEW • Although the well-known success of PPIs in the wide spectrum of all acid-related conditions should not refrain health care professionals to use them when indicated, insufficient attention is given to the multiple adverse effects reported for this class of drugs. • Well designed prospective trials collecting adverse effects are required, since most studies reporting adverse effects are retrospective, are biassed and have methodological issues.
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Affiliation(s)
- An-Sofie Lemmens
- Department of Pediatric Gastroenterology, UZ Brussels, KidZ Health Castle, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090, Brussels, Belgium
- Department of Pediatrics, Ziekenhuis Oost-Limburg (ZOL), Genk, Belgium
| | - Koen Huysentruyt
- Department of Pediatric Gastroenterology, UZ Brussels, KidZ Health Castle, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090, Brussels, Belgium
| | - Yvan Vandenplas
- Department of Pediatric Gastroenterology, UZ Brussels, KidZ Health Castle, Vrije Universiteit Brussel (VUB), Laarbeeklaan 101, 1090, Brussels, Belgium.
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5
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Shinozaki S, Sakamoto H, Osawa H, Yano T, Yamamoto H. Prevalence and factors associated with web‑like mucus in the stomach after vonoprazan use. Biomed Rep 2025; 22:33. [PMID: 39720291 PMCID: PMC11668135 DOI: 10.3892/br.2024.1911] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2024] [Accepted: 10/16/2024] [Indexed: 12/26/2024] Open
Abstract
The appearance of 'web-like mucus' in the stomach is a novel phenomenon associated with vonoprazan (VPZ) usage, characterized by a descriptive mucus pattern resembling a spider web or net. The present study aimed to determine its prevalence and related factors. In this retrospective observational study, the medical records and endoscopic reports of 547 patients who underwent an esophagogastroduodenoscopy were reviewed. The overall prevalence of web-like mucus was 6% (33/547), with 97% (32/33) of these patients being VPZ users. Specifically, 19% (32/167) of VPZ users exhibited this web-like mucus pattern, which was significantly more prevalent in the VPZ group than in the control (no acid blocker intake), proton pump inhibitor, and histamine-2 receptor antagonist groups. Multivariate analysis identified that VPZ use was positively associated with web-like mucus, while open-type gastric atrophy and multiple white and flat elevated lesions were negatively associated. A retrospective analysis of endoscopic findings before initiating VPZ therapy showed that none of the 32 VPZ users with web-like mucus had exhibited the pattern previously. Furthermore, the Cochran-Armitage trend test indicated no significant association between the duration of VPZ therapy and the prevalence of web-like mucus. In conclusion, web-like mucus in the stomach is strongly associated with VPZ use but is not associated with the duration of VPZ therapy.
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Affiliation(s)
- Satoshi Shinozaki
- Shinozaki Medical Clinic, Utsunomiya, Tochigi 321-3223, Japan
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Hirotsugu Sakamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Hiroyuki Osawa
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Tomonori Yano
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
| | - Hironori Yamamoto
- Division of Gastroenterology, Department of Medicine, Jichi Medical University, Shimotsuke, Tochigi 329-0498, Japan
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Xu XT, Jiang MJ, Fu YL, Xie F, Li JJ, Meng QH. Gut microbiome composition in patients with liver cirrhosis with and without hepatic encephalopathy: A systematic review and meta-analysis. World J Hepatol 2025; 17:100377. [PMID: 39871903 PMCID: PMC11736471 DOI: 10.4254/wjh.v17.i1.100377] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/15/2024] [Revised: 10/26/2024] [Accepted: 11/19/2024] [Indexed: 01/06/2025] Open
Abstract
BACKGROUND The gut microbiome is associated with hepatic encephalopathy (HE), but research results on the gut microbiome characteristics of patients with liver cirrhosis with and without HE are inconsistent. AIM To study the gut microbiota characteristics of patients with liver cirrhosis with and without HE. METHODS We searched the PubMed, Web of Science, EMBASE, and Cochrane databases using two keywords, HE, and gut microbiome. According to the inclusion and exclusion criteria, suitable literature was screened to extract data on the diversity and composition of the fecal microbiota in patients with liver cirrhosis with and without HE. The data were analyzed using RevMan and STATA. RESULTS Seventeen studies were included: (1) A meta-analysis of 7 studies revealed that the Shannon index in liver cirrhosis patients with HE was significantly lower than that in patients without HE [-0.20, 95% confidence interval (CI): -0.28 to -0.13, I2 = 20%]; (2) The relative abundances of Lachnospiraceae (-2.73, 95%CI: -4.58 to -0.87, I2 = 38%) and Ruminococcaceae (-2.93, 95%CI: -4.29 to -1.56, I2 = 0%) in liver cirrhosis patients with HE was significantly lower than those in patients without HE; (3) In patients with HE, Enterococcus, Proteobacteria, Enterococcaceae, and Enterobacteriaceae proportions increased, but Ruminococcaceae, Lachnospiraceae, Prevotellaceae, and Bacteroidetes proportions decreased; (4) Differences in the fecal metabolome between liver cirrhosis patients with and without HE were detected; and (5) Differential gut microbiomes may serve as diagnostic and prognostic tools. CONCLUSION The gut microbiomes of patients with liver cirrhosis with and without HE differ. Some gut microbiomes may distinguish liver cirrhosis patients with or without HE and determine patient prognosis.
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Affiliation(s)
- Xiao-Tong Xu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Min-Jie Jiang
- Department of Infectious Diseases, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan 250000, Shandong Province, China
| | - Yun-Lai Fu
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Fang Xie
- Beijing Institute of Hepatology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Jian-Jun Li
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China
| | - Qing-Hua Meng
- Interventional Therapy Center for Oncology, Beijing YouAn Hospital, Capital Medical University, Beijing 100069, China.
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Sharma P, Singh S, Singh AV, Das K, Bhaskar Y, Goel I, Singh H, Das R. Alteration of gastric microbiota in Helicobacter pylori - infected individuals suffering from gastroesophageal reflux disease, duodenal ulcer, and gastritis. INDIAN J PATHOL MICR 2025; 68:61-68. [PMID: 38847202 DOI: 10.4103/ijpm.ijpm_1015_23] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2023] [Accepted: 04/23/2024] [Indexed: 04/01/2025] Open
Abstract
BACKGROUND/AIM Helicobacter pylori ( H. pylori ) colonization affects the gastric microbiome, causing gastrointestinal (GI) diseases. Modern sequencing technology provides insights into GI microbe interaction with H. pylori and their metabolic pathways in causing GI diseases. We aim to compare the gastric microbiota alteration due to H. pylori infection in patients suffering from GI diseases. MATERIALS AND METHODS Genomic DNA were isolated from gastric antrum tissue from 37 H . pylori -infected patients diagnosed with GERD, duodenal ulcers, and gastritis. We conducted the genomic library preparation and sequencing of the amplified product using 16S rRNA NGS analysis. Using microbiome analyst tool diversity analysis, random forest analysis and ANOVA were conducted to find out the comparison of microbial abundance. We have also conducted functional pathway prediction analysis using PICRUSt. RESULTS Metagenomic analysis shows high bacterial diversity in H. pylori -positive gastritis patients. Streptococcus infantis and Neisseria subflava were significantly higher in duodenal ulcer (DU) and gastritis groups. Acinetobacter lwoffii and Helicobacter pullorum were significantly high in the gastritis group only. The functional metabolic pathway analyses revealed that gastroesophageal reflux disease (GERD) samples were significantly enriched with the energy metabolism and xenobiotic biodegradation and metabolism pathways, whereas fructose-1,6-bisphosphatase III was found less in gastritis and DU groups. CONCLUSION There is a difference in microbiota composition in different disease outcomes. We found positive association between microbial diversity and H. pylori in gastritis group only, whereas negative association was found in DU and GERD groups. The functional metabolic pathway analysis revealed significant differences in various disease outcomes.
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Affiliation(s)
- Prateek Sharma
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Sarika Singh
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Aditya V Singh
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
| | - Kunal Das
- Department of Gastroenterology, Yashoda Super Specialty Hospital, Ghaziabad, Uttar Pradesh, India
- Department of Gastroenterology, Max Super-Specialty Hospital, Vaishali, Ghaziabad, Uttar Pradesh, India
| | - Yogendra Bhaskar
- ICMR-AIIMS Computational Genomics Centre, Division of Biomedical Informatics, Indian Council of Medical Research (ICMR), New Delhi, India
| | - Isha Goel
- Department of Psychiatry, All India Institute of Medical Sciences, New Delhi, India
| | - Harpreet Singh
- ICMR-AIIMS Computational Genomics Centre, Division of Biomedical Informatics, Indian Council of Medical Research (ICMR), New Delhi, India
| | - Rajashree Das
- Center for Medical Biotechnology, Amity Institute of Biotechnology, Amity University, Noida, Uttar Pradesh, India
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Zeber-Lubecka N, Kulecka M, Dabrowska M, Kluska A, Piątkowska M, Turkot MH, Pilonis ND, Yusuf A, Nowicki-Osuch K, Mikula M, Ostrowski J. Dysbiosis of the Upper Gastrointestinal Tract in Head-and-Neck Cancer Survivors: A Pilot Study Using the Capsule Sponge Device. Cancers (Basel) 2024; 16:3528. [PMID: 39456621 PMCID: PMC11506215 DOI: 10.3390/cancers16203528] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2024] [Revised: 10/15/2024] [Accepted: 10/17/2024] [Indexed: 10/28/2024] Open
Abstract
BACKGROUND A non-endoscopic capsule-sponge device allows sampling the entire length of the esophagus. Here, we compared microbiomes of the oral cavity, esophagus, and gastric corpus collected by oral swab, capsule-sponge device, and endoscopic biopsy, respectively, in patients representing three distinct risk profiles for esophageal squamous cell carcinoma (ESCC). METHODS The study enrolled 11 patients with esophageal squamous intraepithelial neoplasia, 21 patients after curative treatment for head and neck squamous cell cancer (HNSCC) (HNSCC survivors), and 40 patients with functional dyspeptic (FD) symptoms. Microbial genomic DNA was analyzed using 16S rRNA gene amplicon sequencing. RESULTS The Shannon index of the capsule-sponge sample microbiota was significantly higher in FD group than in patients after treatment for HNSCC, and the Chao index of gastric samples differed between HNSCC survivors and FD patients. Analysis of the β-diversity of FD patients, HNSCC, and esophageal squamous intraepithelial neoplasia showed that different genera formed at each location. The abundance of 205, 116, and 9 genera differed between FD patients and HNSCC survivors in the gastric, capsule-sponge, and oral samples, respectively; 33 genera differed between the FD group and patients with esophageal squamous intraepithelial neoplasia in capsule-sponge samples. CONCLUSIONS The bacterial communities of the upper digestive tract were clustered according to the anatomic site. Despite substantial differences in gastric and esophageal microbiota samples between FD patients and HNSCC survivors, the microbial members and diversity showed small differences between FD patients and those with esophageal squamous intraepithelial neoplasia. It remains unclear whether gastric and esophageal dysbiosis is associated with or is a consequence of treatment for HNSCC.
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Affiliation(s)
- Natalia Zeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Maria Kulecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Michalina Dabrowska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Anna Kluska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Magdalena Piątkowska
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Maryla Helena Turkot
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Cancer Prevention, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Nastazja Dagny Pilonis
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Gastrointestinal Oncology, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland
| | - Aisha Yusuf
- Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge CB2 1TN, UK;
| | | | - Michal Mikula
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
| | - Jerzy Ostrowski
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, 02-781 Warsaw, Poland; (N.Z.-L.); (M.K.); (M.H.T.); (N.D.P.)
- Department of Genetics, Maria Sklodowska-Curie National Research Institute of Oncology, 02-781 Warsaw, Poland; (M.D.); (A.K.); (M.P.); (M.M.)
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Kaneko H, Sato H, Suzuki Y, Ikeda A, Kuwashima H, Ikeda R, Sato T, Irie K, Sue S, Maeda S. A Novel Characteristic Gastric Mucus Named "Web-like Mucus" Potentially Induced by Vonoprazan. J Clin Med 2024; 13:4070. [PMID: 39064109 PMCID: PMC11277586 DOI: 10.3390/jcm13144070] [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: 04/01/2024] [Revised: 05/27/2024] [Accepted: 07/09/2024] [Indexed: 07/28/2024] Open
Abstract
Background: In the absence of Helicobacter pylori (HP) infection, a characteristic gastric mucus adhesion may appear during the use of vonoprazan. We named this novel characteristic mucus "web-like mucus" (WLM). This study aimed to determine the incidence and risk factors for WLM. Methods: Between January 2017 and January 2022, 5665 patients were enrolled in this study. The patients were divided into a proton-pump inhibitor (PPI)-prescribed group (n = 2000), a vonoprazan-prescribed group (n = 268), and a no-PPI/vonoprazan-prescribed (n = 3397) group, and the presence of WLM was examined. After excluding four patients with autoimmune gastritis, the remaining 264 patients in the vonoprazan group were divided into WLM and non-WLM groups, and their clinical features were analyzed. Results: A total of 55 (21%) patients had WLM, all in the vonoprazan-prescribed group. There were no significant differences in factors such as, sex, age, chronic kidney disease, diabetes mellitus, HP eradication history, smoking, or alcohol consumption between the WLM and non-WLM groups. The median duration from the start of vonoprazan administration to the endoscopic detection of WLM was 2 (1-24) months. Conclusions: WLM appears to be a characteristic feature in patients treated with vonoprazan.
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Affiliation(s)
- Hiroaki Kaneko
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Hiroki Sato
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Yuichi Suzuki
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Aya Ikeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Hirofumi Kuwashima
- Yokohama Hodogaya Central Hospital, 43-1 Kamadai-Chou Hodogaya-Ku, Yokohama 240-8585, Japan;
| | - Ryosuke Ikeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Takeshi Sato
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Kuniyasu Irie
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Soichiro Sue
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
| | - Shin Maeda
- Department of Gastroenterology, Yokohama City University Graduate School of Medicine, 3-9 Fukuura Kanazawa-Ku, Yokohama 236-0004, Japan; (H.K.); (H.S.); (Y.S.); (A.I.); (R.I.); (T.S.); (K.I.); (S.S.)
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10
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Liu Q, Wang X, Engstrand L, Sadr-Azodi O, Fall K, Brusselaers N. Maintenance proton pump inhibitor use and risk of colorectal cancer: a Swedish retrospective cohort study. BMJ Open 2024; 14:e079591. [PMID: 38960460 PMCID: PMC11227764 DOI: 10.1136/bmjopen-2023-079591] [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: 09/05/2023] [Accepted: 05/21/2024] [Indexed: 07/05/2024] Open
Abstract
OBJECTIVES We aimed to evaluate the risk of colorectal adenocarcinoma (CRA) associated with long-term use of proton pump inhibitors (PPIs) in a large nationwide cohort. DESIGN Retrospective cohort study. SETTING This research was conducted at the national level, encompassing the entire population of Sweden. PARTICIPANTS This study utilised Swedish national registries to identify all adults who had ≥180 days of cumulative PPI use between July 2005 and December 2012, excluding participants who were followed up for less than 1 year. A total of 754 118 maintenance PPI users were included, with a maximum follow-up of 7.5 years. INTERVENTIONS Maintenance PPI use (cumulative≥180 days), with a comparator of maintenance histamine-2 receptor antagonist (H2RA) use. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome measure was the risk of CRA, presented as standardised incidence ratios (SIRs) with 95% confidence intervals (CIs). Subgroup analyses were performed to explore the impact of indications, tumour locations, tumour stages and the duration of follow-up. A multivariable Poisson regression model was fitted to estimate the incidence rate ratios (IRRs) and 95% CIs of PPI versus H2RA use. RESULTS Maintenance PPI users exhibited a slightly elevated risk of CRA compared to the general population (SIR 1.10, 95% CI=1.06 to 1.13) for both men and women. Individuals aged 18-39 (SIR 2.79, 95% CI=1.62 to 4.47) and 40-49 (SIR 2.02, 95% CI=1.65 to 2.45) had significantly higher risks than the general population. Right-sided CRA showed a higher risk compared to the general population (SIR 1.26, 95% CI=1.20 to 1.32). There was no significant difference in the risk of CRA between maintenance PPI users and maintenance H2RA users (IRR 1.05, 95% CI=0.87 to 1.27, p<0.05). CONCLUSIONS Maintenance PPI use may be associated with an increased risk of CRA, but a prolonged observation time is needed.
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Affiliation(s)
- Qing Liu
- Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Xinchen Wang
- Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden
| | - Lars Engstrand
- Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
| | - Omid Sadr-Azodi
- Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden
- Department of Surgery, Capio Saint Göran Hospital, Stockholm, Sweden
| | - Katja Fall
- Clinical Epidemiology and Biostatistics School of Medical Sciences, Örebro University, Örebro, Sweden
- Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
| | - Nele Brusselaers
- Department of Microbiology, Tumour and Cell Biology, Karolinska Institutet, Stockholm, Sweden
- Department of Head and Skin, Ghent University, Ghent, Belgium
- Global Health Institute, Antwerp University, Antwerp, Belgium
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11
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Kim H, Nzabarushimana E, Huttenhower C, Chan AT, Nguyen LH. Altered Microbial Transcription in Long-term Proton Pump Inhibitor Use: Findings From a United States Cohort Study. Gastroenterology 2024; 167:405-408.e3. [PMID: 38521094 PMCID: PMC11193639 DOI: 10.1053/j.gastro.2024.03.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/20/2023] [Revised: 03/12/2024] [Accepted: 03/18/2024] [Indexed: 03/25/2024]
Affiliation(s)
- Hanseul Kim
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Etienne Nzabarushimana
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Curtis Huttenhower
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Broad Institute of MIT and Harvard University, Cambridge, Massachusetts; The Harvard Chan Microbiome in Public Health Center, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts; Department of Immunology and Infectious Diseases, T.H. Chan School of Public Health, Harvard University, Boston, Massachusetts
| | - Andrew T Chan
- Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts
| | - Long H Nguyen
- Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, Massachusetts; Clinical and Translational Epidemiology Unit, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts; Division of Gastroenterology, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts.
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12
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Corriero A, Giglio M, Soloperto R, Inchingolo F, Varrassi G, Puntillo F. Microbial Symphony: Exploring the Role of the Gut in Osteoarthritis-Related Pain. A Narrative Review. Pain Ther 2024; 13:409-433. [PMID: 38678155 PMCID: PMC11111653 DOI: 10.1007/s40122-024-00602-9] [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: 02/22/2024] [Accepted: 04/03/2024] [Indexed: 04/29/2024] Open
Abstract
One of the most common musculoskeletal disorders, osteoarthritis (OA), causes worldwide disability, morbidity, and poor quality of life by degenerating articular cartilage, modifying subchondral bone, and inflaming synovial membranes. OA pathogenesis pathways must be understood to generate new preventative and disease-modifying therapies. In recent years, it has been acknowledged that gut microbiota (GM) can significantly contribute to the development of OA. Dysbiosis of GM can disrupt the "symphony" between the host and the GM, leading to a host immunological response that activates the "gut-joint" axis, ultimately worsening OA. This narrative review summarizes research supporting the "gut-joint axis" hypothesis, focusing on the interactions between GM and the immune system in its two main components, innate and adaptive immunity. Furthermore, the pathophysiological sequence of events that link GM imbalance to OA and OA-related pain is broken down and further investigated. We also suggest that diet and prebiotics, probiotics, nutraceuticals, exercise, and fecal microbiota transplantation could improve OA management and represent a new potential therapeutic tool in the light of the scarce panorama of disease-modifying osteoarthritis drugs (DMOADs). Future research is needed to elucidate these complex interactions, prioritizing how a particular change in GM, i.e., a rise or a drop of a specific bacterial strain, correlates with a certain OA subset to pinpoint the associated signaling pathway that leads to OA.
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Affiliation(s)
- Alberto Corriero
- Department of Interdisciplinary Medicine - ICU Section, University of Bari Aldo Moro, Piazza G. Cesare 11, 70124, Bari, Italy.
| | - Mariateresa Giglio
- Department of Interdisciplinary Medicine - ICU Section, University of Bari Aldo Moro, Piazza G. Cesare 11, 70124, Bari, Italy
| | - Rossana Soloperto
- Department of Intensive Care, Brussels' University Hospital (HUB), Rue de Lennik 808, 1070, Brussels, Belgium
| | - Francesco Inchingolo
- Department of Interdisciplinary Medicine, University of Bari "Aldo Moro", 70124, Bari, Italy
| | | | - Filomena Puntillo
- Department of Interdisciplinary Medicine - ICU Section, University of Bari Aldo Moro, Piazza G. Cesare 11, 70124, Bari, Italy.
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13
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Garg K, Mohajeri MH. Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review. Brain Res Bull 2024; 207:110883. [PMID: 38244807 DOI: 10.1016/j.brainresbull.2024.110883] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2023] [Revised: 01/12/2024] [Accepted: 01/16/2024] [Indexed: 01/22/2024]
Abstract
The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.
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Affiliation(s)
- Kirti Garg
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland
| | - M Hasan Mohajeri
- Institute of Anatomy, University of Zurich, Winterthurerstrasse 190, CH 8057 Zurich, Switzerland.
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14
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Varma S, Trudeau SJ, Li J, Freedberg DE. Proton pump Inhibitors and Risk of Enteric Infection in Inflammatory Bowel Disease: A Self-controlled Case Series. Inflamm Bowel Dis 2024; 30:38-44. [PMID: 36917215 PMCID: PMC11491639 DOI: 10.1093/ibd/izad035] [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: 07/17/2022] [Indexed: 03/16/2023]
Abstract
BACKGROUND We tested whether proton pump inhibitors (PPIs) are associated with enteric infections among those with inflammatory bowel disease (IBD), after adequately accounting for baseline differences between PPI users and nonusers. METHODS This was a self-controlled case series, with each patient serving as their own control. Ambulatory patients with IBD were included if they were tested for enteric infection by multiplex polymerase chain reaction testing panel (GIPCR) and/or Clostridoides difficile toxin PCR from 2015 to 2019 and received PPIs for some but not all of this period. Rates of enteric infections were compared between the PPI-exposed period vs pre- and post-PPI periods identical in duration to the exposed period. Conditional Poisson regression was used to adjust for time-varying factors. RESULTS Two hundred twenty-one IBD patients were included (49% ulcerative colitis, 46% Crohn's disease, and 5% indeterminate colitis). The median PPI duration was 7 months (interquartile range 4 to 11 months). A total of 25 (11%) patients had a positive GIPCR or C. difficile test in the PPI period, 9 (4%) in the pre-PPI period, and 8 (4%) in the post-PPI period. Observed incidence rates for enteric infections were 2.5, 7.4, and 2.2 per 100 person years for the pre-PPI, PPI, and post-PPI periods, respectively (adjusted incidence rate ratios, 2.8; 95% confidence interval [CI] 1.3-6.0) for PPI vs pre-PPI and 2.9 (95% CI, 1.3-6.4) for PPI vs post-PPI). The adjusted absolute excess risk associated with PPIs was 4.9 infections per 100 person years. CONCLUSIONS Proton pump inhibitors were associated with a 3-fold increased risk for enteric infection among those with IBD but had a modest absolute risk.
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Affiliation(s)
- Sanskriti Varma
- Division of Gastroenterology, Massachusetts General Hospital, Boston, MA, USA
| | - Stephen J Trudeau
- Columbia Vagelos College of Physicians and Surgeons, New York, NY, USA
| | - Jianhua Li
- Biomedical Informatics, Columbia University Irving Medical Center, New York, NY, USA
| | - Daniel E Freedberg
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Irving Medical Center, New York, NY, USA
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15
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Bailey S, Fraser K. Advancing our understanding of the influence of drug induced changes in the gut microbiome on bone health. Front Endocrinol (Lausanne) 2023; 14:1229796. [PMID: 37867525 PMCID: PMC10588641 DOI: 10.3389/fendo.2023.1229796] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/27/2023] [Accepted: 08/07/2023] [Indexed: 10/24/2023] Open
Abstract
The gut microbiome has been implicated in a multitude of human diseases, with emerging evidence linking its microbial diversity to osteoporosis. This review article will explore the molecular mechanisms underlying perturbations in the gut microbiome and their influence on osteoporosis incidence in individuals with chronic diseases. The relationship between gut microbiome diversity and bone density is primarily mediated by microbiome-derived metabolites and signaling molecules. Perturbations in the gut microbiome, induced by chronic diseases can alter bacterial diversity and metabolic profiles, leading to changes in gut permeability and systemic release of metabolites. This cascade of events impacts bone mineralization and consequently bone mineral density through immune cell activation. In addition, we will discuss how orally administered medications, including antimicrobial and non-antimicrobial drugs, can exacerbate or, in some cases, treat osteoporosis. Specifically, we will review the mechanisms by which non-antimicrobial drugs disrupt the gut microbiome's diversity, physiology, and signaling, and how these events influence bone density and osteoporosis incidence. This review aims to provide a comprehensive understanding of the complex interplay between orally administered drugs, the gut microbiome, and osteoporosis, offering new insights into potential therapeutic strategies for preserving bone health.
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Affiliation(s)
- Stacyann Bailey
- Department of Biomedical Engineering, University of Massachusetts Amherst, Amherst, MA, United States
- Institute for Applied Life Sciences, University of Massachusetts Amherst, Amherst, MA, United States
| | - Keith Fraser
- Department of Biological Sciences, Rensselaer Polytechnic Institute, Troy, NY, United States
- Center for Biotechnology and Interdisciplinary Studies, Rensselaer Polytechnic Institute, Troy, NY, United States
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16
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Zhai C, Lu F, Du X, Zhang M, Zhang Y, Ma Y, Zhao Y, Huang H, Kang Z. Green carbon dots derived from Atractylodes macrocephala: A potential nanodrug for treating alcoholic gastric ulcer. Colloids Surf B Biointerfaces 2023; 230:113492. [PMID: 37556883 DOI: 10.1016/j.colsurfb.2023.113492] [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: 05/26/2023] [Revised: 07/18/2023] [Accepted: 08/02/2023] [Indexed: 08/11/2023]
Abstract
Alcoholic gastric ulcer is a common acute gastric injury disease. The drugs currently used in clinical practice not only cannot fundamentally treat gastric injury, but also have serious side effects. There is an urgent demand for the discovery of a mild drug to treat alcoholic gastric ulcers. Herein, the green carbon dots derived from charred Atractylodes macrocephala (CAM-CDs) were acquired and have been proven to be safe and effective in alleviating alcoholic gastric ulcers at an inhibition rate up to 60%. CAM-CDs can markedly attenuate the gastric mucosa damage such as mucosal defect, bleeding and inflammatory cell infiltration by histopathological examination. Serum and tissue inflammatory cytokine measurements, as well as immunohistochemistry results, indicate that its mechanism of gastric mucosal protection may involve the reduction of IL-1β and TNF-α by regulating inflammatory signaling pathway of the NF-κB/NLRP3 axis, as well as elevation of IL-10 levels. CAM-CDs also can reduce oxidative stress markers (MDA), increase PGE2 and mucin secretion (MUC5AC), and it simultaneously exerts slight inhibition of hydrogen potassium ATPase and pepsin activity to protect gastric mucosa, as well as increases the microbial diversity and regulates species composition of gut microbiota in rats with gastric ulcer. Our work provides a new perspective on utilizing carbon-based nanomaterials in the development of new mild drugs.
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Affiliation(s)
- Changming Zhai
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Fang Lu
- School of Life Sciences, Beijing University of Chinese Medicine, Beijing 100029, China
| | - Xin Du
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China
| | - Mengling Zhang
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China; Macao Institute of Materials Science and Engineering (MIMSE), MUST-SUDA Joint Research Center for Advanced Functional Materials, Macau University of Science and Technology, Taipa 999078, Macao, China
| | - Yue Zhang
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China
| | - Yurong Ma
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China
| | - Yan Zhao
- School of Traditional Chinese Medicine, Beijing University of Chinese Medicine, Beijing 100029, China.
| | - Hui Huang
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China.
| | - Zhenhui Kang
- Institute of Functional Nano and Soft Materials Laboratory (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou 215123, Jiangsu, China; Macao Institute of Materials Science and Engineering (MIMSE), MUST-SUDA Joint Research Center for Advanced Functional Materials, Macau University of Science and Technology, Taipa 999078, Macao, China.
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17
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Zhang J, Zhang C, Zhang Q, Yu L, Chen W, Xue Y, Zhai Q. Meta-analysis of the effects of proton pump inhibitors on the human gut microbiota. BMC Microbiol 2023; 23:171. [PMID: 37337143 DOI: 10.1186/s12866-023-02895-w] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2023] [Accepted: 05/16/2023] [Indexed: 06/21/2023] Open
Abstract
Mounting evidence has linked changes in human gut microbiota to proton pump inhibitor (PPI) use. Accordingly, multiple studies have analyzed the gut microbiomes of PPI users, but PPI-microbe interactions are still understudied. Here, we performed a meta-analysis of four studies with available 16S rRNA gene amplicon sequencing data to uncover the potential changes in human gut microbes among PPI users. Despite some differences, we found common features of the PPI-specific microbiota, including a decrease in the Shannon diversity index and the depletion of bacteria from the Ruminococcaceae and Lachnospiraceae families, which are crucial short-chain fatty acid-producers. Through training based on multiple studies, using a random forest classification model, we further verified the representativeness of the six screened gut microbial genera and 20 functional genes as PPI-related biomarkers, with AUC values of 0.748 and 0.879, respectively. Functional analysis of the PPI-associated 16S rRNA microbiome revealed enriched carbohydrate- and energy-associated genes, mostly encoding fructose-1,6-bisphosphatase and pyruvate dehydrogenase, among others. In this study, we have demonstrated alterations in bacterial abundance and functional metabolic potential related to PPI use, as a basis for future studies on PPI-induced adverse effects.
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Affiliation(s)
- Jiayi Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Chengcheng Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Qingsong Zhang
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Leilei Yu
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Wei Chen
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Yuzheng Xue
- Department of Gastroenterology, Affiliated Hospital of Jiangnan University, Jiangsu Province, Wuxi, China.
| | - Qixiao Zhai
- State Key Laboratory of Food Science and Technology, Jiangnan University, Wuxi, Jiangsu, 214122, People's Republic of China.
- School of Food Science and Technology, Jiangnan University, Wuxi, 214122, Jiangsu, China.
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18
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Chen Y, Xia SY, Ru FX, Feng JJ, Tao J, Wei ZY, Li X, Qian C, Lin Q, Chen JH. Gastric juice microbiota in pediatric chronic gastritis that clinically tested positive and negative for Helicobacter pylori. Front Microbiol 2023; 14:1112709. [PMID: 37180270 PMCID: PMC10168005 DOI: 10.3389/fmicb.2023.1112709] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/30/2022] [Accepted: 02/28/2023] [Indexed: 05/16/2023] Open
Abstract
Purpose Helicobacter pylori (HP) infection is an identified risk factor for pediatric chronic gastritis (PCG), but its impact on gastric juice microbiota (GJM) remains to be further elucidated in PCG. This study aimed to analyze and compare the microbial communities and microbial interactive networks of GJM in PCG that clinically tested positive and negative for HP (HP+ and HP-, respectively). Methods A total of 45 PCG patients aged from 6 to 16 years were recruited, including 20 HP+ and 25 HP- patients tested by culture and rapid urease test. Gastric juice samples were collected from these PCG patients and subjected to high-throughput amplicon sequencing and subsequent analysis of 16S rRNA genes. Results While no significant change in alpha diversity, significant differences in beta diversity were observed between HP+ and HP- PCG. At the genus level, Streptococcus, Helicobacter, and Granulicatella were significantly enriched in HP+ PCG, whereas Campylobacter and Absconditabacteriales (SR1) were significantly enriched in HP- PCG. Network analysis showed that Streptococcus was the only genus positively correlated with Helicobacter (r = 0.497) in the GJM network of overall PCG. Moreover, compared to HP- PCG, HP+ PCG showed a reduction in microbial network connectivity in GJM. Netshift analysis identified driver microbes including Streptococcus and other four genera, which substantially contributed to the GJM network transition from HP- PCG to HP+ PCG. Furthermore, Predicted GJM function analysis indicated up-regulated pathways related to the metabolism of nucleotides, carbohydrates, and L-Lysine, the urea cycle, as well as endotoxin peptidoglycan biosynthesis and maturation in HP+ PCG. Conclusion GJM in HP+ PCG exhibited dramatically altered beta diversity, taxonomic structure, and function, with reduced microbial network connectivity, which could be involved in the disease etiology.
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Affiliation(s)
- Ying Chen
- Department of Gastroenterology, Affiliated Children’s Hospital of Jiangnan University, Wuxi, China
| | - Shou-Yue Xia
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Fu-Xia Ru
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Jun-Jie Feng
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Ji Tao
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Zhi-Yuan Wei
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
| | - Xiu Li
- Laboratory Animal Center, Jiangnan University, Wuxi, Jiangsu, China
| | - Chengjia Qian
- Department of General Surgery, Affiliated Hospital of Jiangnan University, Wuxi, China
| | - Qiong Lin
- Department of Gastroenterology, Affiliated Children’s Hospital of Jiangnan University, Wuxi, China
| | - Jian-Huan Chen
- Laboratory of Genomic and Precision Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, Jiangsu, China
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Wu CC, Liao MH, Kung WM, Wang YC. Proton Pump Inhibitors and Risk of Chronic Kidney Disease: Evidence from Observational Studies. J Clin Med 2023; 12:2262. [PMID: 36983271 PMCID: PMC10052387 DOI: 10.3390/jcm12062262] [Citation(s) in RCA: 4] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Revised: 03/11/2023] [Accepted: 03/13/2023] [Indexed: 03/17/2023] Open
Abstract
Previous epidemiological studies have raised the concern that the use of proton pump inhibitors (PPIs) is associated with an increased risk of kidney diseases. To date, no comprehensive meta-analysis has been conducted to assess the association between PPIs and the risk of chronic kidney disease (CKD). Therefore, we conducted a systematic review and meta-analysis to address the association between PPIs and CKD. The primary search was conducted in the most popular databases, such as PubMed, Scopus, and Web of Science. All observational studies evaluated the risk of CKD among PPI users, and non-users were considered for inclusion. Two reviewers conducted data extraction and assessed the risk of bias. Random-effect models were used to calculate pooled effect sizes. A total of 6,829,905 participants from 10 observational studies were included. Compared with non-PPI use, PPI use was significantly associated with an increased risk of CKD (RR 1.72, 95% CI: 1.02-2.87, p = 0.03). This updated meta-analysis showed that PPI was significantly associated with an increased risk of CKD. Association was observed in the same among moderate-quality studies. Until further randomized control trials (RCTs) and biological studies confirm these results, PPI therapy should not stop patients with gastroesophageal reflux disease (GERD). However, caution should be used when prescribing to patients with high-risk kidney disease.
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Affiliation(s)
- Chieh-Chen Wu
- Department of Healthcare Information and Management, School of Health Technology, Ming Chuan University, Taoyuan 33300, Taiwan
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan
| | - Mao-Hung Liao
- Superintendent Office, Yonghe Cardinal Tien Hospital, New Taipei City 23148, Taiwan
| | - Woon-Man Kung
- Department of Exercise and Health Promotion, College of Kinesiology and Health, Chinese Culture University, Taipei 11114, Taiwan
- Division of Neurosurgery, Department of Surgery, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei City 23142, Taiwan
| | - Yao-Chin Wang
- Department of Emergency, Min-Sheng General Hospital, Taoyuan 33044, Taiwan
- Graduate Institute of Injury Prevention and Control, College of Public Health, Taipei Medical University, Taipei 11031, Taiwan
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Effect of Antacid Use on Immune Checkpoint Inhibitors in Advanced Solid Cancer Patients: A Systematic Review and Meta-analysis. J Immunother 2023; 46:43-55. [PMID: 36301729 DOI: 10.1097/cji.0000000000000442] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/18/2022] [Accepted: 09/08/2022] [Indexed: 11/07/2022]
Abstract
The influence of antacids use on immune checkpoint inhibitor (ICI) efficacy remains unclear. A systematic review and meta-analysis was performed to evaluate the effect of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) on ICI efficacy in advanced solid cancer patients. A systematic literature search in PubMed, EMBASE, and Web of Science was performed to retrieve studies investigating the effect of antacid use on ICI efficacy. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR), and immune-related adverse events were measured using hazard ratios (HRs) or odds ratios (ORs). Thirty studies enrolling 16,147 advanced cancer patients receiving ICI treatment were included. The pooled analysis indicated that PPI use was associated with shorter OS (HR=1.40, 95% CI, 1.25-1.57) and PFS (HR=1.34, 95% CI, 1.19-1.52) in advanced cancer patients treated with ICIs. PPI use did not show effect on ORR or immune-related adverse event of advanced cancer patients receiving ICI treatment. OS, PFS, and ORR did not differ between H2RA users and non-H2RA users. In subgroup analyses, PPI use was associated with shorter OS and PFS in NSCLC and urothelial carcinoma patients and in patients treated with anti-programmed cell death 1 or anti-programmed cell death ligand 1 monotherapy. In addition, ICI efficacy was different in the antacid exposure time frame subgroups. In conclusion, PPI use has a negative effect on OS and PFS among advanced cancer patients receiving ICI treatment. PPIs should be cautiously administered among advanced cancer patients treated with ICI. The safety of H2RAs and the influence of H2RAs on ICI efficacy need further investigation.
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Proton Pump Inhibitor Pantoprazole Modulates Intestinal Microbiota and Induces TLR4 Signaling and Fibrosis in Mouse Liver. Int J Mol Sci 2022; 23:ijms232213766. [PMID: 36430244 PMCID: PMC9693486 DOI: 10.3390/ijms232213766] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Revised: 10/21/2022] [Accepted: 11/02/2022] [Indexed: 11/12/2022] Open
Abstract
Proton pump inhibitors (PPIs) are one of the most prescribed drugs around the world. PPIs induce microbiota modulation such as obesity both in humans and in animal models. However, since PPIs can induce microbiota modulation despite the absence of a high-fat diet or weight gain, it is an interesting model to correlate microbiota modulation with the establishment of non-alcoholic fatty liver disease (NAFLD). We investigated the effect of pantoprazole treatment on TLR4 signaling and liver histology in C57BL/6J mice for 60 days, trying to correlate microbiota modulation with some aspects of liver injury. We performed glucose (GTT) and insulin (ITT) tolerance tests, serum lipopolysaccharide (LPS) dosage, liver histology, liver and intestine extraction for Western blot and qPCR. Fecal microbiota were investigated via metagenomics. Chronic treatment with pantoprazole induced microbiota modulation and impaired ileum barrier integrity, without an association with insulin resistance. Furthermore, increased circulating LPS and increased Toll-like receptor 4 (TLR4) and TGFβ downstream signaling may have an important role in the development of the observed liver microvesicular steatosis and fibrosis. Finally, this model of PPI-induced changes in microbiota might be useful to investigate liver microvesicular steatosis and fibrosis.
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22
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Angerami Almeida K, de Queiroz Andrade E, Burns G, Hoedt EC, Mattes J, Keely S, Collison A. The microbiota in eosinophilic esophagitis: A systematic review. J Gastroenterol Hepatol 2022; 37:1673-1684. [PMID: 35730344 PMCID: PMC9544137 DOI: 10.1111/jgh.15921] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2022] [Revised: 05/14/2022] [Accepted: 06/14/2022] [Indexed: 12/12/2022]
Abstract
Eosinophilic esophagitis (EoE) is an atopic disease of the esophagus that has shown a significant increase in incidence and prevalence in the last 20 years. The etiology of EoE is unclear, and few studies explore the esophageal microbiota in EoE. The local microbiome has been implicated in the pathogenesis of several allergic and inflammatory diseases, such as asthma and eczema. In this study, we performed a systematic review to evaluate differences in the microbiota profile of patients with EoE compared with controls. MEDLINE, Embase, Cochrane Library, Scopus, and CINAHL (Cumulative Index to Nursing and Allied Health Literature) databases were searched to identify studies investigating the microbiota composition in EoE. Three reviewers screened the articles for eligibility and quality. Seven articles underwent full-text review, and a narrative synthesis was undertaken. The microbiota of the mouth and esophagus are correlated. Patients with active EoE present increased esophageal microbial load and increased abundance in particular species, such as Haemophilus and Aggregatibacter. On the other hand, EoE patients present a decrease in Firmicutes. High microbial load and abundance of Haemophilus are observed in EoE patients, but little evidence exists to demonstrate their influence on inflammation and disease. Understanding microbial signatures in EoE might contribute to the development of novel therapeutic strategies.
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Affiliation(s)
- Kaylani Angerami Almeida
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,Priority Research Centre GrowUpWell, Hunter Medical Research InstituteUniversity of NewcastleNewcastleNew South WalesAustralia,Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) ProgramHunter Medical Research Institute (HMRI)New Lambton HeightsNew South WalesAustralia,NHMRC Centre of Research Excellence (CRE) in Digestive HealthThe University of NewcastleCallaghanNew South WalesAustralia
| | - Ediane de Queiroz Andrade
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,Priority Research Centre GrowUpWell, Hunter Medical Research InstituteUniversity of NewcastleNewcastleNew South WalesAustralia,Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) ProgramHunter Medical Research Institute (HMRI)New Lambton HeightsNew South WalesAustralia
| | - Grace Burns
- NHMRC Centre of Research Excellence (CRE) in Digestive HealthThe University of NewcastleCallaghanNew South WalesAustralia,School of Biomedical Sciences and Pharmacy, College of Health, Medicine and WellbeingThe University of NewcastleCallaghanNew South WalesAustralia
| | - Emily C Hoedt
- NHMRC Centre of Research Excellence (CRE) in Digestive HealthThe University of NewcastleCallaghanNew South WalesAustralia,School of Biomedical Sciences and Pharmacy, College of Health, Medicine and WellbeingThe University of NewcastleCallaghanNew South WalesAustralia
| | - Joerg Mattes
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,Priority Research Centre GrowUpWell, Hunter Medical Research InstituteUniversity of NewcastleNewcastleNew South WalesAustralia,Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) ProgramHunter Medical Research Institute (HMRI)New Lambton HeightsNew South WalesAustralia
| | - Simon Keely
- NHMRC Centre of Research Excellence (CRE) in Digestive HealthThe University of NewcastleCallaghanNew South WalesAustralia,School of Biomedical Sciences and Pharmacy, College of Health, Medicine and WellbeingThe University of NewcastleCallaghanNew South WalesAustralia
| | - Adam Collison
- School of Medicine and Public HealthUniversity of NewcastleNewcastleNew South WalesAustralia,Priority Research Centre GrowUpWell, Hunter Medical Research InstituteUniversity of NewcastleNewcastleNew South WalesAustralia,Viruses, Infection, Immunity, Vaccine and Asthma (VIVA) ProgramHunter Medical Research Institute (HMRI)New Lambton HeightsNew South WalesAustralia
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23
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Li X, He F, Tuo X, Qiu Y, Guo J, Wu Y, Meng X, Yang Z. Electroacupuncture ameliorates peptic ulcer disease in association with gastroduodenal microbiota modulation in mice. Front Cell Infect Microbiol 2022; 12:935681. [PMID: 36061878 PMCID: PMC9437313 DOI: 10.3389/fcimb.2022.935681] [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] [Subscribe] [Scholar Register] [Received: 05/06/2022] [Accepted: 07/28/2022] [Indexed: 02/02/2023] Open
Abstract
Peptic ulcer disease (PUD) is a common disease and frequently encountered in the clinic. Accumulating evidence suggests that PUD is associated with the gastrointestinal microbiota. Electroacupuncture (EA) is an improved version of acupuncture, which can improve the clinical effect by increasing the stimulation and delivering appropriate electrical pulses to needles. This method has been widely used in the treatment of peptic ulcer disease. However, its effect on gastrointestinal microbiota remains unclear. Therefore, in the present study, the ameliorative effect of EA was evaluated on the gastroduodenal mucosa, and the regulatory effect of the gastroduodenal microbiota was assessed in PUD mice. A total of 48 male Kun Ming mice were randomly divided into the following groups: normal control group (NC), PUD model group (PUD), Shousanli group (LI10), and Zusanli group (ST36) (n=12). The mice in groups LI10 and ST36 were treated with EA at LI10 and ST36, respectively. This intervention was continued for 7 days. Subsequently, we evaluated the morphological changes in the gastric and duodenal mucosa, and specific indices were measured, including the contents of serum dopamine (DA), the trefoil factor (TFF), and the vasoactive intestinal peptide (VIP). In addition, the gastric and duodenal microbiota were assessed via 16S ribosomal DNA sequencing. The results indicated that EA at LI10 or ST36 significantly reduced the injury of the gastroduodenal mucosa in PUD mice. The gastric microbial community structure of the groups LI10 and ST36 was similar to that of the NC group following comparison with the microbial community structure of the PUD model group. Moreover, the abundance of Firmicutes in the stomach was decreased, whereas that of Bacteroidetes was increased, and the abundance of Firmicutes in the duodenum was decreased. Furthermore, the microbial diversity and richness of the gastric microbiota in group LI10 were also significantly increased, and the serum dopamine and trefoil factor levels in group ST36 were significantly increased. Therefore, it is suggested that EA ameliorating PUD is in association with improving the levels of DA and TFF and regulating the relative abundances of Firmicutes and Bacteroidetes in the gastric microbiota.
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Affiliation(s)
- Xiaoshuang Li
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Feiyu He
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Xuan Tuo
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Yuanming Qiu
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Jingjing Guo
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Yiming Wu
- Eye Institute, School of Medicine, Xiamen University, Xiamen, China
| | - Xianjun Meng
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
| | - Zongbao Yang
- Department of Traditional Chinese Medicine, School of Medicine, Xiamen University, Xiamen, China
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24
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Malfertheiner P, Megraud F, Rokkas T, Gisbert JP, Liou JM, Schulz C, Gasbarrini A, Hunt RH, Leja M, O'Morain C, Rugge M, Suerbaum S, Tilg H, Sugano K, El-Omar EM. Management of Helicobacter pylori infection: the Maastricht VI/Florence consensus report. Gut 2022; 71:gutjnl-2022-327745. [PMID: 35944925 DOI: 10.1136/gutjnl-2022-327745] [Citation(s) in RCA: 594] [Impact Index Per Article: 198.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/29/2022] [Accepted: 06/21/2022] [Indexed: 01/06/2023]
Abstract
Helicobacter pyloriInfection is formally recognised as an infectious disease, an entity that is now included in the International Classification of Diseases 11th Revision. This in principle leads to the recommendation that all infected patients should receive treatment. In the context of the wide clinical spectrum associated with Helicobacter pylori gastritis, specific issues persist and require regular updates for optimised management.The identification of distinct clinical scenarios, proper testing and adoption of effective strategies for prevention of gastric cancer and other complications are addressed. H. pylori treatment is challenged by the continuously rising antibiotic resistance and demands for susceptibility testing with consideration of novel molecular technologies and careful selection of first line and rescue therapies. The role of H. pylori and antibiotic therapies and their impact on the gut microbiota are also considered.Progress made in the management of H. pylori infection is covered in the present sixth edition of the Maastricht/Florence 2021 Consensus Report, key aspects related to the clinical role of H. pylori infection were re-evaluated and updated. Forty-one experts from 29 countries representing a global community, examined the new data related to H. pylori infection in five working groups: (1) indications/associations, (2) diagnosis, (3) treatment, (4) prevention/gastric cancer and (5) H. pylori and the gut microbiota. The results of the individual working groups were presented for a final consensus voting that included all participants. Recommendations are provided on the basis of the best available evidence and relevance to the management of H. pylori infection in various clinical fields.
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Affiliation(s)
- Peter Malfertheiner
- Medical Department 2, LMU, Munchen, Germany
- Department of Radiology, LMU, Munchen, Germany
| | - Francis Megraud
- INSERM U853 UMR BaRITOn, University of Bordeaux, Bordeaux, France
| | - Theodore Rokkas
- Gastroenterology, Henry Dunant Hospital Center, Athens, Greece
- Medical School, European University, Nicosia, Cyprus
| | - Javier P Gisbert
- Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa (IP), Madrid, Spain
- Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Jyh-Ming Liou
- Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Christian Schulz
- Medical Department 2, LMU, Munchen, Germany
- Partner Site Munich, DZIF, Braunschweig, Germany
| | - Antonio Gasbarrini
- Medicina Interna e Gastroenterologia, Fondazione Policlinico Universitario Gemelli IRCCS, Università Cattolica del Sacro Cuore Facoltà di Medicina e Chirurgia, Roma, Italy
| | - Richard H Hunt
- Medicine, McMaster University, Hamilton, Ontario, Canada
- Farncombe Family Digestive Health Research Institute, Hamilton, Ontario, Canada
| | - Marcis Leja
- Faculty of Medicine, University of Latvia, Riga, Latvia
- Institute of Clinical and Preventive Medicine, University of Latvia, Riga, Latvia
| | - Colm O'Morain
- Faculty of Health Sciences, Trinity College Dublin, Dublin, Ireland
| | - Massimo Rugge
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Padova, Italy
- Veneto Tumor Registry (RTV), Padova, Italy
| | - Sebastian Suerbaum
- Partner Site Munich, DZIF, Braunschweig, Germany
- Max von Pettenkofer Institute, LMU, Munchen, Germany
| | - Herbert Tilg
- Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology & Metabolism, Medizinische Universitat Innsbruck, Innsbruck, Austria
| | - Kentaro Sugano
- Department of Medicine, Jichi Medical School, Tochigi, Japan
| | - Emad M El-Omar
- Department of Medicine, University of New South Wales, Sydney, New South Wales, Australia
- School of Medicine and Dentistry, University of Aberdeen, Aberdeen, UK
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25
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Trenaman SC, Harding A, Bowles SK, Kirkland SA, Andrew MK. A Prescribing Cascade of Proton Pump Inhibitors Following Anticholinergic Medications in Older Adults With Dementia. Front Pharmacol 2022; 13:878092. [PMID: 35814221 PMCID: PMC9257131 DOI: 10.3389/fphar.2022.878092] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Accepted: 05/30/2022] [Indexed: 11/25/2022] Open
Abstract
Introduction: Prescribing cascade refers to use of a medication to treat a drug-related adverse event. Prescribing cascades increase medication use, cost, and risk of adverse events. Objective: Our objective was to use administrative health data to identify whether use of medications from the anticholinergic cognitive burden scale was associated with proton pump inhibitor (PPI) prescribing consistent with a prescribing cascade in older adults with dementia. Method: The cohort was comprised of Nova Scotia Seniors’ Pharmacare beneficiaries identified to have dementia and medication dispensation data recorded between 1 April 2010, or cohort entry and 31 March 2015. Anticholinergic medications from the anticholinergic cognitive burden scale (ACB) were abstracted. A look back period of 365 days identified if a PPI had been dispensed preceding anticholinergic dispensation. PPI initiation within 30, 60, 90, or 180 days of the anticholinergic medication was assessed. Demographic description of those dispensed anticholinergic medications or PPIs were reported. Risk factors for the prescribing cascade were investigated with logistic regression and Cox proportional hazards modelling including a sex-stratified analysis. Results: We identified 28,952 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia and prescription dispensation data. Anticholinergic medications were frequently dispensed with 63.4% of the cohort dispensed at least one prescription for an anticholinergic medication. The prescribing cascade defined as up to 180-days between anticholinergic medication inititation and PPI dispensation, occurred in 1,845 Nova Scotia Seniors’ Pharmacare beneficiaries with dementia (incidence 6.4%). Multivariate regression showed those experiencing the prescribing cascade after initiating any anticholinergic were younger (OR 0.98, 95%CI [0.97–0.98]), less likely to live in an urban location (OR 0.82, 95%CI [0.74–0.91]), or to be men (OR 0.74, 95%CI [0.67–0.82]). Cox regression demonstrated an increased risk of starting a PPI within 180 days when initiating any medication from the ACB (HR 1.38, 95%CI [1.29–1.58]). Discussion: Regression modelling suggested that anticholinergic medications increased the risk of PPI dispensation consistent with a prescribing cascade in the cohort. The identification of the prescribing cascade in this population of older Nova Scotia Seniors’ Pharmacare Program beneficiaries with dementia using administrative health data highlights how routinely collected health data can be used to identify prescribing cascades.
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Affiliation(s)
- Shanna C. Trenaman
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- *Correspondence: Shanna C. Trenaman,
| | | | - Susan K. Bowles
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- Nova Scotia Health, Halifax, NS, Canada
- College of Pharmacy, Dalhousie University, Halifax, NS, Canada
| | - Susan A. Kirkland
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- Department of Community Health and Epidemiology, Dalhousie University, Halifax, NS, Canada
| | - Melissa K. Andrew
- Department of Medicine, Dalhousie University, Halifax, NS, Canada
- Nova Scotia Health, Halifax, NS, Canada
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26
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Wang M, Lu D, Bi M. Influence of concomitant gastric acid suppressants use on the survival of patients with non-small cell lung cancer treated with programmed death-1/ligand-1 inhibitors: A meta-analysis. Int Immunopharmacol 2022; 110:108955. [PMID: 35750017 DOI: 10.1016/j.intimp.2022.108955] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/17/2022] [Revised: 06/06/2022] [Accepted: 06/10/2022] [Indexed: 11/05/2022]
Abstract
INTRODUCTION Influence of concomitant use of gastric acid suppressants (GAS) on survival of non-small cell lung cancer (NSCLC) patients receiving programmed death-1/ligand-1 (PD-1/PD-L1) inhibitors has rarely been comprehensively evaluated. A meta-analysis was performed to systematically evaluate the effect of concomitant GAS in NSCLC patients receiving PD-1/PD-L1inhibitors. METHODS Relevant observational studies were identified by search of Medline, Embase, and Web of Science databases from inception to May 26, 2022. A random-effect model which incorporates the possible between-study heterogeneity was used to combine the results. RESULTS Ten retrospective and one prospective cohort studies including 5892 patients were patients were included. Influence of concomitant proton pump inhibitors (PPIs) was evaluated in ten studies, and influence of GAS, including PPIs or histamine type-2 receptor antagonists were evaluated in one study. Pooled results showed that concomitant use of GAS was associated with worse progression-free survival (PFS, adjusted hazard ratio [HR]: 1.32, 95% confidence interval [CI]: 1.20 to 1.45, P < 0.001; I2 = 0%) and overall survival (OS, adjusted HR: 1.36, 95% CI: 1.26 to 1.48, P < 0.001; I2 = 0%) in NSCLC patients taking PD-1/PD-L1inhibitors. Subgroup analyses indicated that the association between concomitant use of GAS and poor survival in NSCLC patients taking PD-L1inhibitors was consistent in univariate and multivariate studies (P values for subgroup difference both > 0.05 for PFS and OS). CONCLUSIONS The meta-analysis by summarizing the up-to-date literatures showed that use of GAS, primarily PPIs, may be associated with poor survival outcomes in patients with NSCLC receiving PD-1/PD-L1inhibitors.
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Affiliation(s)
- Mingyu Wang
- Department of Oncology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China; Department of Respiratory Disease, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - Depeng Lu
- Department of Gastroenterology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China
| | - Minghong Bi
- Department of Oncology, the First Affiliated Hospital of Bengbu Medical College, Bengbu 233000, China.
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27
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Berreta A, Kopper J. Equine probiotics-what are they, where are we and where do we need to go? J Equine Vet Sci 2022; 115:104037. [DOI: 10.1016/j.jevs.2022.104037] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/06/2021] [Revised: 05/03/2022] [Accepted: 06/06/2022] [Indexed: 11/26/2022]
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Czerwińska-Rogowska M, Skonieczna-Żydecka K, Kaseja K, Jakubczyk K, Palma J, Bott-Olejnik M, Brzozowski S, Stachowska E. Kitchen Diet vs. Industrial Diets-Impact on Intestinal Barrier Parameters among Stroke Patients. INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH 2022; 19:ijerph19106168. [PMID: 35627704 PMCID: PMC9141131 DOI: 10.3390/ijerph19106168] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/13/2022] [Revised: 05/15/2022] [Accepted: 05/16/2022] [Indexed: 12/10/2022]
Abstract
Background and aims: Strokes are the second highest cause of death in the world and the most common cause of permanent disability in adults. Intestinal barrier permeability thus contributes to diminished homeostasis within the body, which further affects the healing process and convalescence. Each stroke patient should be administered with ingredients that support the intestinal barrier (e.g., protein and fiber). The aim of this study was to compare the effect of various types of diet (enteral with or without fiber vs. a mixed kitchen diet) on the metabolic activity of intestinal microbiota, namely short chain fatty acids, and gut barrier integrity parameters (zonulin and calprotectin. Methods: Patients (n = 59), after suffering an ischemic stroke, were randomly allocated to three groups receiving: the kitchen diet (n = 32; 1.2 g fiber in 100 mL); Nutrison Energy® (n = 14; 0.02 g fiber in 100 mL); and Nutrison Diason Energy HP® (n = 13; 1.8 g fiber in 100 mL). The patients underwent anthropometric measurements and blood samples (for prealbumin measurements), and stool samples (for zonulin and calprotectin determinations) were taken twice, on admission and a week later. Results: Industrial diets enriched with fiber maintained nutritional status and had a beneficial effect on intestinal barrier permeability parameters. Patients fed with kitchen diets demonstrated a decreased number of lymphocytes, hemoglobin, erythrocytes, and increased serum concentration of C-reactive protein, but improved gut barrier markers. Proton pump inhibitors were shown to increase the inflammatory process in gut. Conclusions: Stroke patients should be administered with industrial diets enriched with fiber to improve gut barrier integrity and nutritional parameters.
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Affiliation(s)
- Maja Czerwińska-Rogowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
| | - Karolina Skonieczna-Żydecka
- Department od Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland; (K.S.-Ż.); (J.P.)
| | - Krzysztof Kaseja
- Department of General and Transplant Surgery, Pomeranian Medical University, 71-460 Szczecin, Poland;
| | - Karolina Jakubczyk
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
| | - Joanna Palma
- Department od Biochemical Sciences, Pomeranian Medical University, 71-460 Szczecin, Poland; (K.S.-Ż.); (J.P.)
| | - Marta Bott-Olejnik
- Neurology Department Regional Specialist Hospital in Gryfice, 72-300 Gryfice, Poland; (M.B.-O.); (S.B.)
| | - Sławomir Brzozowski
- Neurology Department Regional Specialist Hospital in Gryfice, 72-300 Gryfice, Poland; (M.B.-O.); (S.B.)
| | - Ewa Stachowska
- Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland; (M.C.-R.); (K.J.)
- Correspondence:
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29
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Martin S, Battistini C, Sun J. A Gut Feeling in Amyotrophic Lateral Sclerosis: Microbiome of Mice and Men. Front Cell Infect Microbiol 2022; 12:839526. [PMID: 35360111 PMCID: PMC8963415 DOI: 10.3389/fcimb.2022.839526] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2021] [Accepted: 02/14/2022] [Indexed: 02/06/2023] Open
Abstract
Amyotrophic lateral sclerosis (ALS) is a severely debilitating disease characterized by progressive degeneration of motor neurons. ALS etiology and pathophysiology are not well understood. It could be the consequences of complex interactions among host factors, microbiome, and the environmental factors. Recent data suggest the novel roles of intestinal dysfunction and microbiota in ALS etiology and progression. Although microbiome may indeed play a critical role in ALS pathogenesis, studies implicating innate immunity and intestinal changes in early disease pathology are limited. The gastrointestinal symptoms in the ALS patients before their diagnosis are largely ignored in the current medical practice. This review aims to explore existing evidence of gastrointestinal symptoms and progress of microbiome in ALS pathogenesis from human and animal studies. We discuss dietary, metabolites, and possible therapeutic approaches by targeting intestinal function and microbiome. Finally, we evaluate existing evidence and identify gaps in the knowledge for future directions in ALS. It is essential to understanding the microbiome and intestinal pathogenesis that determine when, where, and whether microbiome and metabolites critical to ALS progression. These studies will help us to develop more accurate diagnosis and better treatment not only for this challenging disease, but also for other neurodegenerative diseases.
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Affiliation(s)
- Sarah Martin
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Carolina Battistini
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
| | - Jun Sun
- Division of Gastroenterology and Hepatology, Department of Medicine, University of Illinois at Chicago, Chicago, IL, United States
- Department of Microbiology and Immunology, University of Illinois at Chicago, Chicago, IL, United States
- University of Illinois at Chicago (UIC) Cancer Center, University of Illinois at Chicago, Chicago, IL, United States
- Jesse Brown VA Medical Center, Chicago, IL, United States
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30
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Leopold SR, Abdelraouf K, Nicolau DP, Agresta H, Johnson J, Teter K, Dunne WM, Broadwell D, van Belkum A, Schechter LM, Sodergren EJ, Weinstock GM. Murine Model for Measuring Effects of Humanized-Dosing of Antibiotics on the Gut Microbiome. Front Microbiol 2022; 13:813849. [PMID: 35250930 PMCID: PMC8892246 DOI: 10.3389/fmicb.2022.813849] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2021] [Accepted: 01/13/2022] [Indexed: 11/29/2022] Open
Abstract
There is a current need for enhancing our insight in the effects of antimicrobial treatment on the composition of human microbiota. Also, the spontaneous restoration of the microbiota after antimicrobial treatment requires better understanding. This is best addressed in well-defined animal models. We here present a model in which immune-competent or neutropenic mice were administered piperacillin-tazobactam (TZP) according to human treatment schedules. Before, during and after the TZP treatment, fecal specimens were longitudinally collected at established intervals over several weeks. Gut microbial taxonomic distribution and abundance were assessed through culture and molecular means during all periods. Non-targeted metabolomics analyses of stool samples using Quadrupole Time of Flight mass spectrometry (QTOF MS) were also applied to determine if a metabolic fingerprint correlated with antibiotic use, immune status, and microbial abundance. TZP treatment led to a 5–10-fold decrease in bacterial fecal viability counts which were not fully restored during post-antibiotic follow up. Two distinct, relatively uniform and reproducible restoration scenarios of microbiota changes were seen in post TZP-treatment mice. Post-antibiotic flora could consist of predominantly Firmicutes or, alternatively, a more diverse mix of taxa. In general, the pre-treatment microbial communities were not fully restored within the screening periods applied. A new species, closely related to Eubacterium siraeum, Mageeibacillus indolicus, and Saccharofermentans acetigenes, became predominant post-treatment in a significant proportion of mice, identified by 16S rRNA gene sequencing. Principal component analysis of QTOF MS of mouse feces successfully distinguished treated from non-treated mice as well as immunocompetent from neutropenic mice. We observe dynamic but distinct and reproducible responses in the mouse gut microbiota during and after TZP treatment and propose the current murine model as a useful tool for defining the more general post-antibiotic effects in the gastro-intestinal ecosystem where humanized antibiotic dosing may ultimately facilitate extrapolation to humans.
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Affiliation(s)
- Shana R. Leopold
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Kamilia Abdelraouf
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States
| | - David P. Nicolau
- Center for Anti-Infective Research and Development, Hartford Hospital, Hartford, CT, United States
| | - Hanako Agresta
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Jethro Johnson
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | - Kathleen Teter
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
| | | | | | - Alex van Belkum
- BioMérieux SA, Clinical Unit, Grenoble, France
- *Correspondence: Alex van Belkum,
| | | | - Erica J. Sodergren
- The Jackson Laboratory for Genomic Medicine, Farmington, CT, United States
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Hamilton MK, Wall ES, Robinson CD, Guillemin K, Eisen JS. Enteric nervous system modulation of luminal pH modifies the microbial environment to promote intestinal health. PLoS Pathog 2022; 18:e1009989. [PMID: 35143593 PMCID: PMC8830661 DOI: 10.1371/journal.ppat.1009989] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2021] [Accepted: 01/07/2022] [Indexed: 01/02/2023] Open
Abstract
The enteric nervous system (ENS) controls many aspects of intestinal homeostasis, including parameters that shape the habitat of microbial residents. Previously we showed that zebrafish lacking an ENS, due to deficiency of the sox10 gene, develop intestinal inflammation and bacterial dysbiosis, with an expansion of proinflammatory Vibrio strains. To understand the primary defects resulting in dysbiosis in sox10 mutants, we investigated how the ENS shapes the intestinal environment in the absence of microbiota and associated inflammatory responses. We found that intestinal transit, intestinal permeability, and luminal pH regulation are all aberrant in sox10 mutants, independent of microbially induced inflammation. Treatment with the proton pump inhibitor, omeprazole, corrected the more acidic luminal pH of sox10 mutants to wild type levels. Omeprazole treatment also prevented overabundance of Vibrio and ameliorated inflammation in sox10 mutant intestines. Treatment with the carbonic anhydrase inhibitor, acetazolamide, caused wild type luminal pH to become more acidic, and increased both Vibrio abundance and intestinal inflammation. We conclude that a primary function of the ENS is to regulate luminal pH, which plays a critical role in shaping the resident microbial community and regulating intestinal inflammation.
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Affiliation(s)
- M. Kristina Hamilton
- Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America
| | - Elena S. Wall
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America
| | - Catherine D. Robinson
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America
| | - Karen Guillemin
- Institute of Molecular Biology, University of Oregon, Eugene, Oregon, United States of America
- Humans and the Microbiome Program, CIFAR, Toronto, Ontario, Canada
- * E-mail: (KG); (JSE)
| | - Judith S. Eisen
- Institute of Neuroscience, University of Oregon, Eugene, Oregon, United States of America
- * E-mail: (KG); (JSE)
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Veettil SK, Sadoyu S, Bald EM, Chandran VP, Khuu SAT, Pitak P, Lee YY, Nair AB, Antony PT, Ford AC, Chaiyakunapruk N. Association of proton-pump inhibitor use with adverse health outcomes: A systematic umbrella review of meta-analyses of cohort studies and randomised controlled trials. Br J Clin Pharmacol 2022; 88:1551-1566. [PMID: 34622475 DOI: 10.1111/bcp.15103] [Citation(s) in RCA: 29] [Impact Index Per Article: 9.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 12/13/2022] Open
Abstract
AIMS The aim was to perform an umbrella review to summarise the existing evidence on proton-pump inhibitor (PPI) use and adverse outcomes and to grade the certainty of evidence. METHODS Electronic databases were searched up to July 2021 for meta-analyses of cohort studies and/or randomised controlled trials (RCTs). Summary effect sizes from a random-effects model, between-study heterogeneity, 95% prediction interval, small-study effect, excess significance and credibility ceilings were devised to classify the credibility of evidence from meta-analyses of cohort studies, whereas the GRADE approach was used for meta-analyses of RCTs. RESULTS In meta-analyses of cohort studies, 52 of the 91 examined associations were statistically significant (P ≤ .05). Convincing evidence emerged from main analysis for the association between PPI use and risk of all-site fracture and chronic kidney disease in the elderly population. However, none of these associations remained supported by convincing evidence after sensitivity analyses. The use of PPI is also associated with an increased risk of mortality due to COVID-19 infection and other related adverse outcomes, but the quality of evidence was weak. In meta-analyses of RCTs, 38 of the 63 examined associations were statistically significant. However, no associations were supported by high or moderate-quality evidence. CONCLUSION This study's findings imply that most putative adverse outcomes associated with PPI use may not be supported by high-quality evidence and are likely to have been affected by underlying confounding factors. Future research is needed to confirm the causal association between PPI use and risk of fracture and chronic kidney disease.
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Affiliation(s)
- Sajesh K Veettil
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
| | - Saranrat Sadoyu
- Department of Pharmacy, Pakchongnana Hospital, Pakchong, Thailand
| | - Elizabeth M Bald
- College of Pharmacy, University of Utah, Salt Lake City, UT, USA
| | - Viji P Chandran
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | | | | | - Yeong Yeh Lee
- School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia
- GI Function and Motility Unit, Hospital USM, Universiti Sains Malaysia, Kota Bharu, Malaysia
| | - Athira Balakrishnan Nair
- Department of Pharmacy Practice, Manipal College of Pharmaceutical Sciences, Manipal Academy of Higher Education, Manipal, Karnataka, India
| | - Paul T Antony
- Department of Rheumatology, Amala Institute of Medical Sciences, Kerala, India
| | - Alexander C Ford
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, UK
- Leeds Institute of Medical Research at St. James's, University of Leeds, Leeds, UK
| | - Nathorn Chaiyakunapruk
- Department of Pharmacotherapy, College of Pharmacy, University of Utah, Salt Lake City, UT, USA
- School of Pharmacy, University of Wisconsin, Madison, WI, USA
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Chen Y, Xueying Z, Jiaqu C, Qiyi C, Huanlong Q, Ning L, Yasong D, Xiaoxin Z, Rong Y, Jubao L, Xiaoqiong L, Chunlian M, Yu W, Shidong C, Guifang K, Dongmei Z, Shuanfeng F, Xujing Z, Binrang Y, Yanxia W, Ling L, Song Y, Xiang Z, Beihua Z, Lin J, Hong J. FTACMT study protocol: a multicentre, double-blind, randomised, placebo-controlled trial of faecal microbiota transplantation for autism spectrum disorder. BMJ Open 2022; 12:e051613. [PMID: 35105621 PMCID: PMC8804636 DOI: 10.1136/bmjopen-2021-051613] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
INTRODUCTION Autism spectrum disorder (ASD) is a complicated diffuse developmental disorder that commonly involves gastrointestinal distress and dysbacteriosis. Emerging lines of evidence have shown faecal microbiota transplantation (FMT) to be a potential therapeutic strategy for improving the clinical outcomes of patients with ASD by re-establishing their intestinal microflora. We are undertaking the first-ever multicentre, double-blind, randomised controlled trial of FMT for the treatment of children with both ASD and gastrointestinal symptoms and will assess the feasibility and efficacy outcomes of this strategy. METHODS In total, 318 children with both ASD and gastrointestinal symptoms will be enrolled (from 15 hospitals in China) to receive either FMT intervention (n=212) or a placebo (control, n=106). Children aged 3-6 years will take two capsules two times a day, and those older than 6 years will take three capsules two times a day. Each patient will receive four treatment courses, with each 12-day course being repeated every month. Outcomes will be evaluated at baseline, throughout the period of intervention, and at subsequent follow-ups for 2 months. The primary trial objective is to investigate the remodelling effect of FMT on the intestinal microflora in patients with ASD. The secondary objective focuses on the clinical efficacy and safety of FMT, including its improvement of the clinical response and metabonomics. ETHICS AND DISSEMINATION Ethical approval was obtained from the hospital Ethics Committee of each Faecal Transfer for ASD China Multicenter Trial Working Group. The ongoing FMT clinical trial is intended to support the approval of the new technology and its administration. The results of this trial will provide high-quality evidence to inform the future clinical application of this new therapy. TRIAL REGISTRATION NUMBER ChiCTR2100043906; Pre-results.
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Affiliation(s)
- Ye Chen
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Zhang Xueying
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Cui Jiaqu
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Chen Qiyi
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Qin Huanlong
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Li Ning
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Du Yasong
- Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai, China
| | - Zhao Xiaoxin
- Child and Adolescent Psychiatry, Shanghai Mental Health Center, Shanghai, China
| | - Yang Rong
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Lu Jubao
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Lv Xiaoqiong
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Ma Chunlian
- Department of Colorectal Diseases, Shanghai Tenth People's Hospital, Shanghai, China
| | - Wang Yu
- Child Healthcare Department, Shanghai Children's Hospital, Shanghai, China
| | - Chen Shidong
- Rehabilitation Medicine Department, Shanghai First People's Hospital, Shanghai, China
| | - Kuang Guifang
- Department of Pediatric Mental Health, Qingdao Women and Children's Hospital, Qingdao, China
| | - Zhao Dongmei
- Institute of Child Health, Qilu Children's Hospital of Shandong University, Jinan, China
| | - Fang Shuanfeng
- Child Healthcare Department, Zhengzhou University Third Hospital and Henan Province Women and Children's Hospital, Zhengzhou, China
| | - Zhang Xujing
- Clinical Psychology, Hebei Mental Health Center, Baoding, China
| | - Yang Binrang
- Child Healthcare Department, Shenzhen Children's Hospital, Shenzhen, China
| | - Wang Yanxia
- Child Healthcare Department, The Affiliated Hospital of Qingdao University, Qingdao, China
| | - Li Ling
- Child Rehabilitation Department, Hainan Women and Children's Medical Center, Haikou, China
| | - Yuan Song
- Psychiatry Department, Zhoushan Second People's Hospital, Zhoushan, China
| | - Zhou Xiang
- Department of Children Psychology, Zhuhai Maternal and Child Health Care Hospital, Zhuhai, China
| | - Zhang Beihua
- Yangzhi Affiliated Rehabilitation Hospital of Tongji University, Shanghai, China
| | - Jiang Lin
- Psychiatry Department, Dalian Seveth People's Hospital, Dalian, China
| | - Ji Hong
- Wuhu No.1 People's Hospital, Anhui, China
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34
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Wauters L, Tito RY, Ceulemans M, Lambaerts M, Accarie A, Rymenans L, Verspecht C, Toth J, Mols R, Augustijns P, Tack J, Vanuytsel T, Raes J. Duodenal Dysbiosis and Relation to the Efficacy of Proton Pump Inhibitors in Functional Dyspepsia. Int J Mol Sci 2021; 22:ijms222413609. [PMID: 34948413 PMCID: PMC8708077 DOI: 10.3390/ijms222413609] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2021] [Revised: 12/15/2021] [Accepted: 12/17/2021] [Indexed: 12/11/2022] Open
Abstract
Proton pump inhibitors (PPI) may improve symptoms in functional dyspepsia (FD) through duodenal eosinophil-reducing effects. However, the contribution of the microbiome to FD symptoms and its interaction with PPI remains elusive. Aseptic duodenal brushings and biopsies were performed before and after PPI intake (4 weeks Pantoprazole 40 mg daily, FD-starters and controls) or withdrawal (2 months, FD-stoppers) for 16S-rRNA sequencing. Between- and within-group changes in genera or diversity and associations with symptoms or duodenal factors were analyzed. In total, 30 controls, 28 FD-starters and 19 FD-stoppers were followed. Mucus-associated Porphyromonas was lower in FD-starters vs. controls and correlated with symptoms in FD and duodenal eosinophils in both groups, while Streptococcus correlated with eosinophils in controls. Although clinical and eosinophil-reducing effects of PPI therapy were unrelated to microbiota changes in FD-starters, increased Streptococcus was associated with duodenal PPI effects in controls and remained higher despite withdrawal of long-term PPI therapy in FD-stoppers. Thus, duodenal microbiome analysis demonstrated differential mucus-associated genera, with a potential role of Porphyromonas in FD pathophysiology. While beneficial effects of short-term PPI therapy were not associated with microbial changes in FD-starters, increased Streptococcus and its association with PPIeffects in controls suggest a role for duodenal dysbiosis after long-term PPI therapy.
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Affiliation(s)
- Lucas Wauters
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Raúl Y. Tito
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Matthias Ceulemans
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Maarten Lambaerts
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Alison Accarie
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Leen Rymenans
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Chloë Verspecht
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
| | - Joran Toth
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Raf Mols
- Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium; (R.M.); (P.A.)
| | - Patrick Augustijns
- Drug Delivery and Disposition, KU Leuven, 3000 Leuven, Belgium; (R.M.); (P.A.)
| | - Jan Tack
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
| | - Tim Vanuytsel
- Department of Gastroenterology and Hepatology, University Hospitals Leuven, 3000 Leuven, Belgium; (L.W.); (J.T.)
- Translational Research in Gastrointestinal Disorders (TARGID), KU Leuven, 3000 Leuven, Belgium; (M.C.); (M.L.); (A.A.); (J.T.)
- Correspondence: (T.V.); (J.R.)
| | - Jeroen Raes
- VIB Center for Microbiology, 3000 Leuven, Belgium; (R.Y.T.); (L.R.); (C.V.)
- Department of Microbiology and Immunology, Rega Institute, KU Leuven, 3000 Leuven, Belgium
- Correspondence: (T.V.); (J.R.)
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Baek YH, Kang EJ, Hong S, Park S, Kim JH, Shin JY. Survival outcomes of patients with nonsmall cell lung cancer concomitantly receiving proton pump inhibitors and immune checkpoint inhibitors. Int J Cancer 2021; 150:1291-1300. [PMID: 34877670 DOI: 10.1002/ijc.33892] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2021] [Revised: 11/21/2021] [Accepted: 12/01/2021] [Indexed: 01/21/2023]
Abstract
Recent evidence suggests that gut microbiota dysbiosis adversely affects the efficacy of immune checkpoint inhibitors (ICIs). Our objective was to investigate the association between concomitant use of proton pump inhibitors (PPIs) and ICIs, and poor prognosis in patients with nonsmall cell lung cancer (NSCLC). We conducted a cohort study using a completely enumerated lung cancer cohort from a nationwide healthcare database in South Korea. We identified 2963 patients treated with ICIs as second-line or later therapy for stage ≥IIIB NSCLC. PPI use was ascertained within 30-days before and on the date of ICI initiation, and nonuse was defined as no prescription of PPIs during this period. Using national vital statistics in South Korea, we assessed the risk of all-cause mortality associated with concomitant PPI use through a propensity score-matched Cox proportional hazard model. Among 1646 patients included after 1:1 propensity score-matching, concomitant PPI use was associated with a 28% increased risk of all-cause mortality, compared to nonuse (adjusted hazard ratio [HR] 1.28; 95% confidence intervals [CIs], 1.13-1.46). We observed an increased risk when we restricted the analysis to new users of PPI (adjusted HR = 1.64; 95% CI = 1.25-2.17). Subgroup analysis showed that PPI use was associated with high mortality risk among patients with viral hepatitis (adjusted HR = 2.72; 95% CI = 1.54-4.78; Pinteraction = .048). Our study indicates that PPI use is associated with poor prognosis in NSCLC patients treated with ICIs. Further prospective studies are required to determine the risk-benefit balance of concomitant use of PPIs and ICIs.
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Affiliation(s)
- Yeon-Hee Baek
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Eun Joo Kang
- Division of Medical Oncology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, South Korea
| | - Soojung Hong
- Department of Internal Medicine, Division of Medical Oncology, National Health Insurance Service Ilsan Hospital, Goyang, South Korea
| | - Sohee Park
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Ju Hwan Kim
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea
| | - Ju-Young Shin
- School of Pharmacy, Sungkyunkwan University, Suwon, South Korea.,Department of Biohealth Regulatory Science, Sungkyunkwan University, Suwon, South Korea.,Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Seoul, South Korea
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The uninvited guests of our microbiome: Helicobacter pylori and Epstein-Barr virus and their role in gastric cancerogenesis. POSTEP HIG MED DOSW 2021. [DOI: 10.2478/ahem-2021-0008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/20/2022] Open
Abstract
Abstract
It is well established that human body is an ecosystem for numerous microorganisms: bacteria, fungi, eukaryotic parasites, and viruses. They form a “microbiome” that under conditions of homeostasis remains in a friendly mutual relationship with the host. However, the composition and diversity of this microbe community is dynamic and can be changed under the influence of environmental factors, such as diet, antibiotic therapy, lifestyle, and the host’s genotype and immunity. The result of gut microbiome dysbiosis can lead even to cancer. The aim of this review is the description of the healthy gastrointestinal microbiome and the role of two infectious agents: Gram-negative bacteria Helicobacter pylori and Epstein-Barr virus in the development of gastric cancer in terms of gut dysbiosis. H. pylori is the most important pathogen of gastric microbiome with clear impact on its diversity. Coinfection with Epstein-Barr virus causes chronic gastritis, and the inflammatory process is significantly increased. The process of carcinogenesis begins with chronic inflammation that causes atrophic gastritis, intestinal metaplasia, dysplasia, and finally cancer. It has been proven that chronic inflammatory infection caused by infectious agents increases the risk of stomach cancer. Molecular methods that are progressively used to explore the human microbiome provide hope that this knowledge will be used for future diagnoses and therapy in the state of its dysbiosis and in cases of gastric cancer.
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Ghosh S, Pramanik S. Structural diversity, functional aspects and future therapeutic applications of human gut microbiome. Arch Microbiol 2021; 203:5281-5308. [PMID: 34405262 PMCID: PMC8370661 DOI: 10.1007/s00203-021-02516-y] [Citation(s) in RCA: 67] [Impact Index Per Article: 16.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2021] [Revised: 07/29/2021] [Accepted: 08/06/2021] [Indexed: 02/06/2023]
Abstract
The research on human gut microbiome, regarded as the black box of the human body, is still at the stage of infancy as the functional properties of the complex gut microbiome have not yet been understood. Ongoing metagenomic studies have deciphered that the predominant microbial communities belong to eubacterial phyla Firmicutes, Bacteroidetes, Proteobacteria, Fusobacteria, Cyanobacteria, Verrucomicrobia and archaebacterial phylum Euryarchaeota. The indigenous commensal microbial flora prevents opportunistic pathogenic infection and play undeniable roles in digestion, metabolite and signaling molecule production and controlling host's cellular health, immunity and neuropsychiatric behavior. Besides maintaining intestinal health via short-chain fatty acid (SCFA) production, gut microbes also aid in neuro-immuno-endocrine modulatory molecule production, immune cell differentiation and glucose and lipid metabolism. Interdependence of diet and intestinal microbial diversity suggests the effectiveness of pre- and pro-biotics in maintenance of gut and systemic health. Several companies worldwide have started potentially exploiting the microbial contribution to human health and have translated their use in disease management and therapeutic applications. The present review discusses the vast diversity of microorganisms playing intricate roles in human metabolism. The contribution of the intestinal microbiota to regulate systemic activities including gut-brain-immunity crosstalk has been focused. To the best of our knowledge, this review is the first of its kind to collate and discuss the companies worldwide translating the multi-therapeutic potential of human intestinal microbiota, based on the multi-omics studies, i.e. metagenomics and metabolomics, as ready solutions for several metabolic and systemic disorders.
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Affiliation(s)
- Soma Ghosh
- Kolkata Zonal Center, CSIR-National Environmental Engineering Research Institute, i-8 Sector-C, East Kolkata Township, Kolkata, 700107, India.
| | - Sreemanta Pramanik
- Kolkata Zonal Center, CSIR-National Environmental Engineering Research Institute, i-8 Sector-C, East Kolkata Township, Kolkata, 700107, India
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Ostrowski J, Kulecka M, Zawada I, Żeber-Lubecka N, Paziewska A, Graca-Pakulska K, Dąbkowski K, Skubisz K, Cybula P, Ambrożkiewicz F, Urasińska E, Mikula M, Starzyńska T. The gastric microbiota in patients with Crohn's disease; a preliminary study. Sci Rep 2021; 11:17866. [PMID: 34504159 PMCID: PMC8429686 DOI: 10.1038/s41598-021-97261-z] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/11/2021] [Accepted: 08/23/2021] [Indexed: 11/09/2022] Open
Abstract
The gastric microbiota in Crohn's disease (CD) has not been studied. The purpose of the study was to evaluate differences of stomach microbiota between CD patients and controls. DNA was extracted from gastric mucosal and fluid samples, from 24 CD patients and 19 controls. 16S rRNA gene sequencing identified 1511 operational taxonomic units (OTUs), of which 239 passed the low abundance and low variance filters. All but one CD patients were HP negative. Fifteen bacterial phyla were identified in at least one mucosal or fluid site. Of these, Bacteroidota and Firmicutes accounted for 70% of all phyla. Proteobacteria, Actinobacteriota, and Fusobacteriota combined accounted for 27%. There was significant difference in the relative abundance of Bacteroidota, Proteobacteria, Fusobacteriota, and Campilobacterota between CD patients and controls only in gastric corpus samples. In gastric liquid, there was a significant difference only in Actinobacteriota. Pairwise comparison identified 67 differentially abundant OTUs in at least one site. Of these, 13 were present in more than one comparison, and four differentiating OTUs (Neisseriaceae, Neisseria, Absconditabacteriales, and Microbacteriaceae) were identified at all tested sites. The results reveal significant changes in gastric microbial profiles (beta diversity, phylum, and individual taxa levels) between H. pylori-negative CD patients and controls.
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Affiliation(s)
- Jerzy Ostrowski
- Department of Genetics, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland. .,Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland.
| | - Maria Kulecka
- Department of Genetics, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.,Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Iwona Zawada
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252, Szczecin, Poland
| | - Natalia Żeber-Lubecka
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Agnieszka Paziewska
- Department of Genetics, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland.,Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Katarzyna Graca-Pakulska
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252, Szczecin, Poland
| | - Krzysztof Dąbkowski
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252, Szczecin, Poland
| | - Karolina Skubisz
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Patrycja Cybula
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Filip Ambrożkiewicz
- Department of Genetics, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
| | - Elżbieta Urasińska
- Department of Pathology, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Michał Mikula
- Department of Genetics, Maria Skłodowska-Curie National Research Institute of Oncology, Roentgena 5, 02-781, Warsaw, Poland
| | - Teresa Starzyńska
- Department of Gastroenterology, Pomeranian Medical University in Szczecin, Unii Lubelskiej 1, 71-252, Szczecin, Poland.
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Mousavi T, Nikfar S, Abdollahi M. The pharmacotherapeutic management of duodenal and gastric ulcers. Expert Opin Pharmacother 2021; 23:63-89. [PMID: 34435515 DOI: 10.1080/14656566.2021.1959914] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/20/2022]
Abstract
INTRODUCTION Although the incidence and prevalence of duodenal and gastric ulcers have been declining, it remains challenging for health care systems. Based on the underlying cause, history, and characteristics of ulcers, management is generally provided by administering proton pump inhibitors (PPIs) or antibiotics. AREAS COVERED This article is based on global guidelines and English language literature from the past decade obtained through searches using PubMed, Clinicaltrials.gov, the US FDA, and the Cochrane library. Using a stepwise approach, dose and duration of treatment, drug interactions, warnings and contraindications, adverse effects, and administration points were specified. New drug candidates that may get American and European approvals were also introduced. EXPERT OPINION Despite the wide use of PPIs, their development lags behind the clinical need. There is an absolute requirement to develop third-generation PPIs with higher potency and improved pharmacokinetic and safety profiles. Regarding the antibiotic resistance crisis, including those used against H. pylori, conducting more clinical trials and investigating regional antibiotic resistance are warranted. Potassium competitive acid blockers, ilaprazole, and an H. pylori vaccine all show promise for the future.
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Affiliation(s)
- Taraneh Mousavi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Shekoufeh Nikfar
- Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran.,Evidence-Based Evaluation of Cost-Effectiveness and Clinical Outcomes Group, Pharmaceutical Sciences Research Center (PSRC), and the Pharmaceutical Management and Economics Research Center (PMERC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Pharmacoeconomics and Pharmaceutical Administration, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Abdollahi
- Toxicology and Diseases Group (TDG), Pharmaceutical Sciences Research Center (PSRC), the Institute of Pharmaceutical Sciences (TIPS), Tehran University of Medical Sciences, Tehran, Iran.,Department of Toxicology and Pharmacology, School of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.,Personalized Medicine Research Center, Endocrinology and Metabolism Research Institute, Tehran University of Medical Sciences, Tehran, Iran
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Berreta A, Kopper JJ, Alexander TL, Kogan CJ, Burbick CR. Effect of an In Vitro Proximal Gastrointestinal Tract on Viability of Commercially Available Equine Probiotics. J Equine Vet Sci 2021; 104:103671. [PMID: 34416988 DOI: 10.1016/j.jevs.2021.103671] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/15/2021] [Revised: 05/16/2021] [Accepted: 05/18/2021] [Indexed: 12/19/2022]
Abstract
Probiotics, by definition, are live micro-organisms and should remain viable when they reach the intended site of action which is typically the cecum and/or colon. In humans, probiotics often need enteric protection to survive transit through the proximal gastrointestinal (GI) tract. Typically, equine probiotics do not advertise enteric protection and to the author's knowledge the viability of equine probiotics after exposure to the proximal GI tract has not been evaluated. The objective of this study was to evaluate the effect of an in vitro simulation of the equine proximal GI tract on probiotic viability. We hypothesized that the simulated proximal GI tract would adversely effect microbial viability and that the adverse effects would be partially ameliorated by increasing the gastric pH to 4. A total of 11 products were evaluated of which six had at least one micro-organism that was adversely effected by exposure to the proximal GI tract and four of which had at least one micro-organism that was adversely affected when the gastric pH was increased to 4.0. Results from this study indicate that some micro-organisms in equine probiotics do not appear to be adversely affected by exposure to the equine proximal GI tract.
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Affiliation(s)
- Ana Berreta
- Department of Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA
| | - Jamie J Kopper
- Department of Clinical Sciences, College of Veterinary Medicine, Washington State University, Pullman, WA.
| | - Trevor L Alexander
- Washington Animal Disease Diagnostic Laboratory, Washington State University, Pullman, WA
| | - Clark J Kogan
- Center for Interdisciplinary Statistical Education and Research, Washington State University, Pullman, WA
| | - Claire R Burbick
- Washington Animal Disease Diagnostic Laboratory, Washington State University, Pullman, WA; Department of Veterinary Microbiology and Pathology, Washington State University, Pullman, WA
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41
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Feng Y, Chen CL, Chang YJ, Li YH, Chiou CS, Su LH, Li HC, Yang HP, Chiu CH. Microbiological and genomic investigations of invasive Salmonella enterica serovar Panama from a large outbreak in Taiwan. J Formos Med Assoc 2021; 121:660-669. [PMID: 34294499 DOI: 10.1016/j.jfma.2021.07.002] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/03/2021] [Revised: 04/26/2021] [Accepted: 07/03/2021] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND/PURPOSE Salmonella Panama was considered an invasive non-typhoidal Salmonella (iNTS) serovar. Comprehensive clinical, microbiological, and genomic studies on S. Panama are scarce. We aimed to characterize the clinical and microbiological characteristics of S. Panama infection. Virulence mechanism of S. Panama and other iNTS serovars were also examined. METHODS Based on data from the longitudinal surveillance system for Salmonella deployed in Taiwan since 2004, a case-control study was undertaken to evaluate clinical characteristics of S. Panama infection during an outbreak in 2015-2016. Cellular experiments were conducted to compare pathogenicity of S. Panama and other iNTS with S. Typhimurium. RESULTS Most patients (41/44, 93.2%) infected by S. Panama were <5 years old (median, 1.3 years). The case-control study showed that 28 out of the 41 (68.3%) manifested as bacteremia, compared to S. Typhimurium (11.1%). Patients infected by S. Panama had longer durations of fever (P = 0.005) and hospitalization (P < 0.001). Genomic analyses split the isolates into three clades: two clones caused the outbreak, whereas another one accounted for the sporadic infections before 2015. Cellular experiments revealed that S. Panama and other iNTS serovars showed higher monolayer penetration and intracellular survival within macrophages, compared to S. Typhimurium. CONCLUSION This study confirmed that S. Panama is a clinically invasive serovar. Different iNTS serovars express common virulence phenotypes, but they may acquire invasiveness through distinct expression or combinations of virulence genes.
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Affiliation(s)
- Ye Feng
- Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China; Institute for Translational Medicine, Zhejiang University School of Medicine, Hangzhou, China
| | - Chyi-Liang Chen
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yi-Jung Chang
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Yi-Hua Li
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Chien-Shun Chiou
- Center for Research, Diagnostics and Vaccine Development, Taiwan Centers for Disease Control, Taichung, Taiwan
| | - Lin-Hui Su
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hsin-Chieh Li
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Hsin-Ping Yang
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan
| | - Cheng-Hsun Chiu
- Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan; Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan.
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Zhang J, Che H, Zhang B, Zhang C, Zhou B, Ji H, Xie J, Shi X, Li X, Wang F, Tang X. JianpiQinghua granule reduced PPI dosage in patients with nonerosive reflux disease: A multicenter, randomized, double-blind, double-dummy, noninferiority study. PHYTOMEDICINE : INTERNATIONAL JOURNAL OF PHYTOTHERAPY AND PHYTOPHARMACOLOGY 2021; 88:153584. [PMID: 34119741 DOI: 10.1016/j.phymed.2021.153584] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/20/2020] [Revised: 02/26/2021] [Accepted: 04/25/2021] [Indexed: 06/12/2023]
Abstract
BACKGROUND Proton pump inhibitors (PPIs) play an important role in the treatment of nonerosive reflux disease (NERD), but their long-term and excessive uses have been associated with safety concerns. Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. METHODS A total of 204 patients were randomly assigned to the combination group or PPI group (1:1 ratio). They were given JianpiQinghua (JQ) granules (34.8 g) plus omeprazole (10 mg) plus dummy omeprazole (10 mg) or dummy JQ granules (34.8 g) plus omeprazole (20 mg) daily for 4 weeks. The primary endpoints were the rate of sufficient relief and complete resolution of GERD Q at week 4. Metabonomics and the gut microbiota were also assessed. RESULTS Complete resolution was observed in 40.8% of patients in the combination group and 26.8% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.88; 95% CI, 1.03-3.44; p = 0.039). Sufficient relief was observed in 50% of patients in the combination group and 43.30% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.31; 95% CI, 0.74-2.30; p = 0.35). Three patients had liver dysfunction, one of whom had a mild case and 2 of whom had moderate-to-severe cases in the combination group. Patients in the combination group showed a significant increase in richness and diversity of their gut microbiota compared with those in the PPI group. Metabonomics showed that the combination therapy could correct the glutamate metabolism pathway. CONCLUSION Our findings demonstrate the superior efficacy of JQ granules combined with omeprazole (10 mg) vs. omeprazole (20 mg) in terms of symptom relief in patients with NERD. TRIAL REGISTRATION ClinicalTrials.gov number NCT02892357. Registered on 14 February 2019.
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Affiliation(s)
- Jiaqi Zhang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Hui Che
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Beihua Zhang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Chang Zhang
- Department of Gastroenterology, Oriental Hospital, Beijing University of Chinese Medicine, Beijing, China
| | - Bin Zhou
- Department of Gastroenterology, Guang'anmen Hospital, Chinese Academy of traditional Chinese Medicine, Beijing, China
| | - Haijie Ji
- Shanxi Province Academy of Traditional Chinese Medicine, Taiyuan, China
| | - Jingyi Xie
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China
| | - Xiaoshuang Shi
- Institute of Acupuncture and Moxibustion, Chinese Academy of traditional Chinese Medicine, Beijing, China
| | - Xia Li
- Beijing University of Chinese Medicine, Beijing, China
| | - Fengyun Wang
- Department of Gastroenterology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
| | - Xudong Tang
- China Academy of Chinese Medical Sciences, Beijing, China.
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Liang X, Wang P, Lian K, Han F, Tang Y, Zhang S, Zhang W. APB-13 improves the adverse outcomes caused by TGEV infection by correcting the intestinal microbial disorders in piglets. J Anim Physiol Anim Nutr (Berl) 2021; 106:69-77. [PMID: 34075636 DOI: 10.1111/jpn.13555] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/05/2020] [Revised: 10/09/2020] [Indexed: 12/22/2022]
Abstract
Porcine transmissible gastroenteritis virus (TGEV) is an enteric coronavirus that has caused high morbidity and mortality of piglets worldwide. Previous studies have shown that the TGEV can lead to severe diarrhoea, vomiting and dehydration in 2-week-old piglets and weaned piglets, resulting in a large number of piglet deaths. Antimicrobial peptides have broad-spectrum antimicrobial activity and a strong killing effect on bacteria, especially on the drug-resistant pathogenic bacteria, and it has attracted broad concern. However, there are very few reports on the effect of APB-13 (an antimicrobial peptide) on the intestinal microbes of piglets infected with TGEV. In this study, 16S rRNA gene sequencing was used to compare the microbial phylum and the genus of piglet's enteric microorganism in different experimental groups, and to predict the metabolic function of the microbial flora. At the same time, the apparent digestibility of nutrients, digestive enzyme activity, daily weight gain and survival rate were also measured. TGEV infection could cause the imbalance of intestinal microbes in piglets, and increase of the relative abundance of Proteobacteria, and decrease of the relative abundance of Firmicutes, Bacteroidetes and Actinobacteri. With the addition of APB-13, this problem can be alleviated, which can reduce the relative abundance of Proteobacteria and improve the balance of intestinal microorganisms. At the microbial genus level, after adding APB-13, the relative abundance of Catenibacterium, Enterobacter and Streptococcus in the intestinal tract of piglets infected with TGEV showed significant decrease, while the relative abundance of Lactobacillus and Ruminococcus increased. Finally, we found that APB-13 can significantly increase the activity of digestive enzyme in the intestinal tract of piglet, thereby improving the apparent digestibility of nutrients and the growth performance of piglets. This study demonstrates that APB-13 can alleviate the adverse outcomes caused by TGEV infection by correcting the intestinal microbial disorders.
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Affiliation(s)
- Xiuli Liang
- Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology, Anyang, China.,College of Animal Science and Technology, Shihezi University, Shihezi, China
| | - Pengtao Wang
- College of Animal Husbandry, Henan Agricultural University, Zhengzhou, China
| | - Kaiqi Lian
- Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology, Anyang, China
| | - Fangfang Han
- College of Animal Husbandry, Henan Agricultural University, Zhengzhou, China
| | - Yajie Tang
- Henan Joint International Research Laboratory of Veterinary Biologics Research and Application, Anyang Institute of Technology, Anyang, China
| | - Shouming Zhang
- Anyang City Animal Product Quality Safety Monitoring and Inspection Center, Anyang, China
| | - Wenju Zhang
- College of Animal Science and Technology, Shihezi University, Shihezi, China
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Chan GCK, Wong SH, Ng JKC, Li PKT, Szeto CC, Chow KM. Risk of peritonitis after gastroscopy in peritoneal dialysis patients. Perit Dial Int 2021; 42:162-170. [PMID: 34032173 DOI: 10.1177/08968608211018608] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023] Open
Abstract
BACKGROUND Peritonitis is a common and serious complication of peritoneal dialysis (PD). Translocation of gut bacteria to peritoneum is an important mechanism, which may be enhanced by gastrointestinal endoscopy. METHODS In this retrospective observational cohort study, we identified 450 gastroscopies performed in PD patients within a single centre between 2014 and 2019. Gastroscopy-related peritonitis was defined by peritonitis within 1 week after endoscopy. RESULTS A total of 408 endoscopic episodes in 216 patients were analysed after excluding 42 cases with either pre-existing peritonitis before endoscopy, or concomitant biliary, small bowel or large bowel endoscopy. There were 16 episodes of peritonitis within 1 week of endoscopy (3.9%). One-quarter of cases were polymicrobial (four episodes, 25.0%). Logistic regression model showed that patient's age, number of endoscopic biopsies, and histamine-2 receptor blocker use were independently associated with peritonitis, while prior antibiotics exposure was associated with lower risk of peritonitis, odds ratio 0.23 (95% confidence interval 0.06-0.95; p = 0.04). CONCLUSION Peritonitis can complicate gastroscopy in PD patients and occurs more often in elderly or after repeated biopsy procedures.
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Affiliation(s)
- Gordon Chun-Kau Chan
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Sunny Hei Wong
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Jack Kit-Chung Ng
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Philip Kam-Tao Li
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Cheuk-Chun Szeto
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
| | - Kai-Ming Chow
- Carol and Richard Yu Peritoneal Dialysis Research Centre, Department of Medicine and Therapeutics, Prince of Wales Hospital, The Chinese University of Hong Kong, Shatin, Hong Kong, China
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Impact of the repurposed drug thonzonium bromide on host oral-gut microbiomes. NPJ Biofilms Microbiomes 2021; 7:7. [PMID: 33483519 PMCID: PMC7822857 DOI: 10.1038/s41522-020-00181-5] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2020] [Accepted: 12/14/2020] [Indexed: 12/28/2022] Open
Abstract
Drug repurposing is a feasible strategy for the development of novel therapeutic applications. However, its potential use for oral treatments and impact on host microbiota remain underexplored. Here, we assessed the influences of topical oral applications of a repurposed FDA-approved drug, thonzonium bromide, on gastrointestinal microbiomes and host tissues in a rat model of dental caries designed to reduce cross-contamination associated with coprophagy. Using this model, we recapitulated the body site microbiota that mirrored the human microbiome profile. Oral microbiota was perturbed by the treatments with specific disruption of Rothia and Veillonella without affecting the global composition of the fecal microbiome. However, disturbances in the oral-gut microbial interactions were identified using nestedness and machine learning, showing increased sharing of oral taxon Sutterella in the gut microbiota. Host-tissue analyses revealed caries reduction on teeth by thonzonium bromide without cytotoxic effects, indicating bioactivity and biocompatibility when used orally. Altogether, we demonstrate how an oral treatment using a repurposed drug causes localized microbial disturbances and therapeutic effects while promoting turnover of specific oral species in the lower gut in vivo.
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Plomer M, Iii Perez M, Greifenberg DM. Effect of Bacillus clausii Capsules in Reducing Adverse Effects Associated with Helicobacter pylori Eradication Therapy: A Randomized, Double-Blind, Controlled Trial. Infect Dis Ther 2020; 9:867-878. [PMID: 32897519 PMCID: PMC7680487 DOI: 10.1007/s40121-020-00333-2] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/16/2020] [Indexed: 12/02/2022] Open
Abstract
INTRODUCTION Antibiotic treatment can alter the gut microbiome and cause short-term gastrointestinal adverse effects (AEs). This study assessed the efficacy of lyophilized capsules containing 2 × 109 spores of Bacillus clausii (Enterogermina®; Sanofi Synthelabo) in reducing AEs associated with Helicobacter pylori eradication therapy in Italy. METHODS In this randomized, double-blind, single-center, phase IIIB study, 130 adult outpatients with H. pylori infection were assigned to receive one Enterogermina® capsule or placebo three times daily for 2 weeks (1:1). During week 1, all patients received clarithromycin 500 mg, amoxicillin 1 g, and rabeprazole 20 mg twice daily. The primary efficacy outcome was the presence of diarrhea in week 1. RESULTS A total of 130 patients were randomized. The incidence of diarrhea in week 1 was 29% in the B. clausii group and 48% in the placebo group [relative risk (RR) 0.61; 95% confidence interval (CI) 0.39-0.97; p = 0.03]. The incidence of diarrhea remained lower with B. clausii than with placebo in week 2 (RR 0.38; 95% CI 0.14-1.02; p = 0.0422). In week 1, the number of days without diarrhea was significantly higher in the B. clausii group than in the placebo group (6.25 vs. 5.86; p = 0.0304). In both groups, the number of days without diarrhea increased significantly (p < 0.0001) from week 1 to week 2. A total of three AEs occurred in two patients in the placebo group, but none were serious. CONCLUSIONS Compared with placebo, Enterogermina® reduced the incidence of, and the number of days with, diarrhea in patients receiving H. pylori eradication therapy. Enterogermina® was well tolerated.
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Affiliation(s)
- Manuel Plomer
- Consumer Healthcare, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany
| | - Marcos Iii Perez
- Consumer Healthcare, Sanofi-Aventis Deutschland GmbH, Industriepark Höchst, Frankfurt am Main, Germany
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Perry IE, Sonu I, Scarpignato C, Akiyama J, Hongo M, Vega KJ. Potential proton pump inhibitor-related adverse effects. Ann N Y Acad Sci 2020; 1481:43-58. [PMID: 32761834 DOI: 10.1111/nyas.14428] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2020] [Revised: 05/31/2020] [Accepted: 06/12/2020] [Indexed: 12/11/2022]
Abstract
Proton pump inhibitors (PPIs) are one of the most common medications taken by patients worldwide. PPIs are used to treat acid-related disorders, including gastroesophageal reflux disease, peptic ulcer disease, Helicobacter pylori infection, and nonsteroidal anti-inflammatory drug/stress ulceration. For some of these diseases, long-term treatment is necessary. With such prolonged use, concern and investigation into potential adverse effects has increased. In addition, data are available regarding potential anticancer effects of PPIs, especially regarding solid tumors. The aim of this review is to assess the literature on PPIs with regard to common concerns, such as drug-drug interactions, the intestinal microbiome, dementia and central nervous system disease, and osteoporosis, as well as to highlight potential negative and positive impacts of the drug in cancer.
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Affiliation(s)
- Issac E Perry
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, Georgia
| | - Irene Sonu
- Division of Gastroenterology and Hepatology, Stanford University, Redwood City, California
| | - Carmelo Scarpignato
- Department of Health Sciences, United Campus of Malta, Msida, Malta
- Faculty of Medicine, Chinese University of Hong Kong, ShaTin, Hong Kong
| | - Junichi Akiyama
- Division of Gastroenterology and Hepatology, National Center for Global Health and Medicine, Tokyo, Japan
| | - Michio Hongo
- Department of Comprehensive Medicine, Tohoku University School of Medicine, Sendai, Miyagi, Japan
- Department of Medicine, Kurokawa General Hospital, Kurokawa, Miyagi, Japan
| | - Kenneth J Vega
- Division of Gastroenterology and Hepatology, Augusta University-Medical College of Georgia, Augusta, Georgia
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Mulder M, Radjabzadeh D, Kiefte-de Jong JC, Uitterlinden AG, Kraaij R, Stricker BH, Verbon A. Long-term effects of antimicrobial drugs on the composition of the human gut microbiota. Gut Microbes 2020; 12:1795492. [PMID: 32991820 PMCID: PMC7781642 DOI: 10.1080/19490976.2020.1791677] [Citation(s) in RCA: 27] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
INTRODUCTION Antimicrobial drugs are known to have effects on the human gut microbiota. We studied the long-term temporal relationship between several antimicrobial drug groups and the composition of the human gut microbiota determined in feces samples. METHODS Feces samples were obtained from a community-dwelling cohort of middle-aged and elderly individuals (Rotterdam Study). Bacterial DNA was isolated and sequenced using V3/V4 16 S ribosomal RNA sequencing (Illumina MiSeq). The time between the last prescription of several antimicrobial drug groups and the day of sampling was categorized into 0-12, 12-24, 24-48 and >48 months. The effects of the antimicrobial drug groups on the Shannon alpha-diversity (diversity), the Bray-Curtis beta-diversity (community structure), the Firmicutes/Bacteroidetes (F/B) ratio and individual genera were determined. RESULTS We studied the gut microbiota of 1413 individuals (57.5% female, median age 62.6 years). The alpha-diversity was significantly lower up to 4 years after prescriptions of macrolides and lincosamides. It was also lower in the first year after the use of beta-lactams. The community structure (beta-diversity) of the microbiota was significantly different up to 4 years for macrolides and lincosamides, the first year for beta-lactams and at least the first year for quinolones. For the F/B ratio, drugs with a high anaerobic activity shifted the ratio toward Firmicutes in the first year whereas other antimicrobial drugs shifted the ratio toward Bacteroidetes. CONCLUSION Use of antimicrobial drugs is associated with a shift in the composition of the gut microbiota.These effects differ in strength and duration, depending on the antimicrobial drug group used. These findings should be considered when prescribing antimicrobial drugs.
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Affiliation(s)
- M. Mulder
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands,Youth and Healthcare Inspectorate, Heerlen, The Netherlands
| | - D. Radjabzadeh
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - J. C. Kiefte-de Jong
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands,Department of Public Health and Primary Care, LUMC, The Hague, The Netherlands
| | - A. G. Uitterlinden
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands,Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - R. Kraaij
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands
| | - B. H. Stricker
- Department of Epidemiology, Erasmus MC, Rotterdam, The Netherlands,Youth and Healthcare Inspectorate, Heerlen, The Netherlands,Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands,CONTACT B. H. Stricker Department of Epidemiology, Erasmus MC Rotterdam, PO Box 2040, Rotterdam, CA 3000, The Netherlands
| | - A. Verbon
- Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands,Department of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The Netherlands
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Fisher L, Fisher A, Smith PN. Helicobacter pylori Related Diseases and Osteoporotic Fractures (Narrative Review). J Clin Med 2020; 9:E3253. [PMID: 33053671 PMCID: PMC7600664 DOI: 10.3390/jcm9103253] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2020] [Revised: 09/28/2020] [Accepted: 10/07/2020] [Indexed: 02/06/2023] Open
Abstract
Osteoporosis (OP) and osteoporotic fractures (OFs) are common multifactorial and heterogenic disorders of increasing incidence. Helicobacter pylori (H.p.) colonizes the stomach approximately in half of the world's population, causes gastroduodenal diseases and is prevalent in numerous extra-digestive diseases known to be associated with OP/OF. The studies regarding relationship between H.p. infection (HPI) and OP/OFs are inconsistent. The current review summarizes the relevant literature on the potential role of HPI in OP, falls and OFs and highlights the reasons for controversies in the publications. In the first section, after a brief overview of HPI biological features, we analyze the studies evaluating the association of HPI and bone status. The second part includes data on the prevalence of OP/OFs in HPI-induced gastroduodenal diseases (peptic ulcer, chronic/atrophic gastritis and cancer) and the effects of acid-suppressive drugs. In the next section, we discuss the possible contribution of HPI-associated extra-digestive diseases and medications to OP/OF, focusing on conditions affecting both bone homeostasis and predisposing to falls. In the last section, we describe clinical implications of accumulated data on HPI as a co-factor of OP/OF and present a feasible five-step algorithm for OP/OF risk assessment and management in regard to HPI, emphasizing the importance of an integrative (but differentiated) holistic approach. Increased awareness about the consequences of HPI linked to OP/OF can aid early detection and management. Further research on the HPI-OP/OF relationship is needed to close current knowledge gaps and improve clinical management of both OP/OF and HPI-related disorders.
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Affiliation(s)
- Leon Fisher
- Department of Gastroenterology, Frankston Hospital, Peninsula Health, Melbourne 3199, Australia
| | - Alexander Fisher
- Department of Geriatric Medicine, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
| | - Paul N Smith
- Department of Orthopedic Surgery, The Canberra Hospital, ACT Health, Canberra 2605, Australia;
- Australian National University Medical School, Canberra 2605, Australia
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50
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Babic A, Zhang X, Morales-Oyarvide V, Yuan C, Khalaf N, Khalili H, Lochhead P, Chan AT, Ogino S, Wolpin BM, Wu K, Fuchs CS, Giovannucci EL, Stampfer MJ, Ng K. Acid-suppressive medications and risk of colorectal cancer: results from three large prospective cohort studies. Br J Cancer 2020; 123:844-851. [PMID: 32541871 PMCID: PMC7462971 DOI: 10.1038/s41416-020-0939-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2020] [Revised: 05/05/2020] [Accepted: 05/28/2020] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Despite several plausible biological mechanisms linking proton pump inhibitors (PPIs) and H2 receptor antagonists (H2RAs) with colorectal tumorigenesis, their association with risk of colorectal cancer (CRC) has not been adequately assessed in prospective epidemiological studies. METHODS We evaluated the association of acid-suppressive medication use with CRC risk among 175,871 (PPI) and 208,831 (H2RA) participants from three large prospective cohort studies. Medication use was assessed at baseline and updated biennially. The association was evaluated using multivariate Cox proportional hazards regression models. RESULTS There was no significant association between baseline PPI use (hazard ratio (HR) = 0.89, 95% confidence interval (CI), 0.71-1.12) or PPI use after a lag of 8-10 years (HR = 1.12, 95% CI, 0.78-1.59) with CRC risk. We observed no significant association between H2RA use after a lag of 8-10 years and CRC risk (HR = 1.02, 95% CI, 0.81-1.28), while risk was lower for participants with baseline H2RA use (HR = 0.76, 95% CI, 0.60-0.95). Duration of PPI use or H2RA use was not associated with CRC risk (P-trend = 0.21 and 0.95, respectively). CONCLUSIONS Among participants from three large prospective cohorts, use of PPI or H2RA was not associated with higher risk of colorectal cancer.
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Affiliation(s)
- Ana Babic
- Dana-Farber Cancer Institute, Boston, MA, USA.
| | - Xuehong Zhang
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | | | - Chen Yuan
- Dana-Farber Cancer Institute, Boston, MA, USA
| | - Natalia Khalaf
- Division of Gastroenterology, Hepatology, and Endoscopy, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
| | - Hamed Khalili
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
| | - Paul Lochhead
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
| | - Andrew T Chan
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Clinical and Translational Epidemiology Unit, Department of Medicine, Massachusetts General Hospital, Boston, MA, USA
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
| | - Shuji Ogino
- Dana-Farber Cancer Institute, Boston, MA, USA
- Broad Institute of MIT and Harvard, Cambridge, MA, USA
- Program in MPE Molecular Pathological Epidemiology, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | | | - Kana Wu
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Charles S Fuchs
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Yale Cancer Center, New Haven, CT, USA
- Department of Medicine, Yale School of Medicine, New Haven, CT, USA
- Smilow Cancer Hospital, New Haven, CT, USA
| | - Edward L Giovannucci
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Meir J Stampfer
- Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA
- Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA, USA
| | - Kimmie Ng
- Dana-Farber Cancer Institute, Boston, MA, USA
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