|
1
|
Pădureanu V, Dop D, Caragea DC, Rădulescu D, Pădureanu R, Forțofoiu MC. Cardiovascular and Neurological Diseases and Association with Helicobacter Pylori Infection-An Overview. Diagnostics (Basel) 2024; 14:1781. [PMID: 39202269 PMCID: PMC11353373 DOI: 10.3390/diagnostics14161781] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/12/2024] [Revised: 08/05/2024] [Accepted: 08/14/2024] [Indexed: 09/03/2024] Open
Abstract
This article investigates the link between Helicobacter pylori (H. pylori) infection and cardiovascular and neurological disorders. Recent research suggests that H. pylori may play a role in cardiovascular diseases like atherosclerosis, myocardial infarction, and stroke, as well as neurological diseases including Alzheimer's disease, multiple sclerosis, and Parkinson's disease. Cardiovascular Diseases: H. pylori induces endothelial dysfunction and chronic inflammation, promoting atherosclerotic plaque formation and other cardiac complications. High infection prevalence in cardiovascular patients implies that systemic inflammation from H. pylori accelerates disease progression. Eradication therapies combined with anti-inflammatory and lipid-lowering treatments may reduce cardiovascular risk. Neurological Diseases: H. pylori may contribute to Alzheimer's, multiple sclerosis, and Parkinson's through systemic inflammation, neuroinflammation, and autoimmune responses. Increased infection prevalence in these patients suggests bacterial involvement in disease pathogenesis. The eradication of H. pylori could reduce neuroinflammation and improve outcomes. Discussions and Future Research: Managing H. pylori infection in clinical practice could impact public health and treatment approaches. Further research is needed to clarify these relationships. Longitudinal and mechanistic studies are essential to fully understand H. pylori's role in these conditions. Conclusions: H. pylori infection is a potential risk factor for various cardiovascular and neurological conditions. Additional research is critical for developing effective prevention and treatment strategies. Targeted therapies, including H. pylori eradication combined with anti-inflammatory treatments, could improve clinical outcomes. These findings highlight the need for an integrated clinical approach to include H. pylori evaluation and treatment.
Collapse
Affiliation(s)
- Vlad Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Dalia Dop
- Department of Pediatrics, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Daniel Cosmin Caragea
- Department of Nephrology, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania;
| | - Dumitru Rădulescu
- Department of Surgery, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania
| | - Rodica Pădureanu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| | - Mircea-Cătălin Forțofoiu
- Department of Internal Medicine, University of Medicine and Pharmacy Craiova, 200349 Craiova, Romania; (V.P.); (M.-C.F.)
| |
Collapse
|
|
2
|
Thapa S, Bhattarai A, Shah S, Timsina S, Chand S, Jakimovski D. Helicobacter pylori infection and risk of multiple sclerosis: an updated meta-analysis. Neurol Sci 2024; 45:2539-2548. [PMID: 38243036 DOI: 10.1007/s10072-024-07328-8] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/20/2023] [Accepted: 01/11/2024] [Indexed: 01/21/2024]
Abstract
Numerous studies have proposed that Helicobacter pylori infection may possess a protective effect in terms of future risk of multiple sclerosis (MS), however is poorly evidenced. We performed a systematic review and meta-analysis to obtain the pooled results regarding the prevalence of H. pylori infection in persons with multiple sclerosis (pwMS) and healthy controls. A comprehensive database search was performed in PubMed, Embase, and medRxiv for all relevant literature published from the inception of the databases until the August 1, 2022. The retrieved articles were first screened by title and abstract, followed by full-text screening based on the pre-established eligibility criteria. The risk of bias was assessed using the ROBINS-I tool. Data on the seroprevalence of H. pylori in pwMS and healthy controls was extracted, and a meta-analysis was performed in Review Manager Version 5.4.1. Sub-group analysis was performed in accordance with the geographical distribution (Eastern and Western countries) and the method of detection of H. pylori infection enzyme-linked-immunoassay (ELISA), Immunofluorescence, Immunochromatography). Furthermore, sensitivity analyses and publication bias were determined. The preliminary database search retrieved a total of 822 studies. Seventeen case-control studies with a total of 2721 pwMS and 2245 controls were included as a final sample size for the meta-analysis. The overall risk of bias was moderate. Overall, the rate of H. pylori infection in pwMS was not significantly different than in healthy controls (OR: 0.79 (95% CI = 0.58-1.08); I2 = 79%, p = 0.14). Subgroup analysis revealed that the rate of H. pylori infection among PwMS was not significant in both Eastern and Western countries (OR: 0.75 (95% CI = 0.52-1.08); I2 = 81%, p = 0.12). In contrast, data revealed that the prevalence of H. pylori infection in pwMS was significantly lower than that of control based on studies utilizing ELISA assays detection (OR: 0.71 (95% CI = 0.50-1.00); I2 = 81%, p = 0.05), while no significant difference was seen on studies using other assays than ELISA (OR: 1.19 (95% CI = 0.81-1.77); I2 = 0%, p = 0.38). Our findings of statistically indifferent prevalence of H. pylori infection as compared between pwMS and healthy controls suggested the absence of protective effect for risk of MS following H. pylori infection.
Collapse
Affiliation(s)
- Sangharsha Thapa
- Jacobs Comprehensive MS Treatment and Research Center,, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA
| | - Abhinav Bhattarai
- Institute of Medicine, Tribhuvan University, Maharajgunj, 44600, Nepal
| | - Sangam Shah
- Institute of Medicine, Tribhuvan University, Maharajgunj, 44600, Nepal
| | - Sakchhyam Timsina
- Institute of Medicine, Tribhuvan University, Maharajgunj, 44600, Nepal
| | - Swati Chand
- Rochester General Hospital, Rochester, NY, USA
| | - Dejan Jakimovski
- Jacobs Comprehensive MS Treatment and Research Center,, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, Buffalo, NY, USA.
- Buffalo Neuroimaging Analysis Center, Department of Neurology, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo, State University of New York, 100 High Street , Buffalo, NY, 14203, USA.
| |
Collapse
|
|
3
|
Candelli M, Franza L, Cianci R, Pignataro G, Merra G, Piccioni A, Ojetti V, Gasbarrini A, Franceschi F. The Interplay between Helicobacter pylori and Gut Microbiota in Non-Gastrointestinal Disorders: A Special Focus on Atherosclerosis. Int J Mol Sci 2023; 24:17520. [PMID: 38139349 PMCID: PMC10744166 DOI: 10.3390/ijms242417520] [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: 10/27/2023] [Revised: 12/07/2023] [Accepted: 12/14/2023] [Indexed: 12/24/2023] Open
Abstract
The discovery of Helicobacter pylori (H. pylori) in the early 1980s by Nobel Prize winners in medicine Robin Warren and Barry Marshall led to a revolution in physiopathology and consequently in the treatment of peptic ulcer disease. Subsequently, H. pylori has also been linked to non-gastrointestinal diseases, such as autoimmune thrombocytopenia, acne rosacea, and Raynaud's syndrome. In addition, several studies have shown an association with cardiovascular disease and atherosclerosis. Our narrative review aims to investigate the connection between H. pylori infection, gut microbiota, and extra-gastric diseases, with a particular emphasis on atherosclerosis. We conducted an extensive search on PubMed, Google Scholar, and Scopus, using the keywords "H. pylori", "dysbiosis", "microbiota", "atherosclerosis", "cardiovascular disease" in the last ten years. Atherosclerosis is a complex condition in which the arteries thicken or harden due to plaque deposits in the inner lining of an artery and is associated with several cardiovascular diseases. Recent research has highlighted the role of the microbiota in the pathogenesis of this group of diseases. H. pylori is able to both directly influence the onset of atherosclerosis and negatively modulate the microbiota. H. pylori is an important factor in promoting atherosclerosis. Progress is being made in understanding the underlying mechanisms, which could open the way to interesting new therapeutic perspectives.
Collapse
Affiliation(s)
- Marcello Candelli
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| | - Laura Franza
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| | - Rossella Cianci
- Department of Translational Medicine and Surgery, Catholic University, Fondazione Policlinico Universitario A. Gemelli—IRCCS, 00168 Rome, Italy;
| | - Giulia Pignataro
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| | - Giuseppe Merra
- Biomedicine and Prevention Department, Section of Clinical Nutrition and Nutrigenomics, Facoltà di Medicina e Chirurgia, Università degli Studi di Roma Tor Vergata, 00133 Rome, Italy;
| | - Andrea Piccioni
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| | - Veronica Ojetti
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| | - Antonio Gasbarrini
- Medical, Abdominal Surgery and Endocrine-Metabolic Science Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy;
| | - Francesco Franceschi
- Emergency, Anesthesiological and Reanimation Sciences Department, Fondazione Policlinico Universitario A. Gemelli—IRCCS of Rome, 00168 Rome, Italy; (L.F.); (G.P.); (A.P.); (V.O.); (F.F.)
| |
Collapse
|
|
4
|
Arjmandi D, Graeili Z, Mohammadi P, Arshadi M, Jafari Tadi M, Ardekani A, Naeimi R, Abbasi F, Marhoommirzabak E, Mahjour S, Sartip B, Prasa H, Fallah Omrani V, Rostami A. Chlamydia pneumonia infection and risk of multiple sclerosis: A meta-analysis. Mult Scler Relat Disord 2023; 77:104862. [PMID: 37442074 DOI: 10.1016/j.msard.2023.104862] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2023] [Revised: 06/04/2023] [Accepted: 06/29/2023] [Indexed: 07/15/2023]
Abstract
BACKGROUND The role of infectious agents, including Chlamydia pneumoniae (Cpn), in the development of multiple sclerosis (MS), is still a matter of major contention. OBJECTIVE This meta-analysis study aimed to assess the actual involvement of Cpn in MS development. METHODS We undertook a search of international scientific databases to identify eligible studies. We used a random-effects meta-analysis model (REM) to generate the pooled odds ratio (OR) and 95% confidence intervals (CIs). Heterogeneity was calculated using the I2 statistic. Sensitivity and subgroup analyses were applied to assess the effects of study characteristics and socio-demographic variables on the pooled OR. RESULTS We identified 37 studies comprising 51 datasets that satisfied the inclusion criteria. Considering diagnostic methods for Cpn, 26 and 25 datasets used PCR- and serological-based methods, respectively. In PCR-based datasets, REM showed a significant positive association between Cpn infection and the development of MS (OR, 5.29; 95% CI, 3.12-8.97), while a non-significant positive association was achieved in serological-based datasets (OR, 1.34; 95% CI, 0.88-2.03). In subgroup analyses on PCR-based datasets, results were significant for both CSF (OR, 5.70) and serum (OR, 4.84) samples; both healthy (OR, 16.11) and hospital-based (OR, 2.88) controls; and both moderate (OR, 5.14) and high (OR, 5.48) quality studies. In serological-based datasets, only those that used CSF samples yielded significant results (OR, 3.41). CONCLUSIONS Our findings verify the significant positive relationship between Cpn infection and MS. We advocate prospective cohort studies with lifelong follow-ups and also experimental studies to better understand the role of Cpn in MS development.
Collapse
Affiliation(s)
- Delaram Arjmandi
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Zahra Graeili
- Department of Biostatistics and Epidemiology, School of Medicine, Babol University of Medical Sciences, Babol, Iran
| | - Parisa Mohammadi
- Department of Internal Medicine, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Mahdi Arshadi
- Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Mehrdad Jafari Tadi
- Department of Cell and Molecular Medicine, Rush University Medical Center, Chicago, IL 60607, USA
| | - Ali Ardekani
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Reza Naeimi
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Farzaneh Abbasi
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Elika Marhoommirzabak
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu city, 600 Cebu, Philippines
| | - Sanaz Mahjour
- Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Behnam Sartip
- Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, IL 60611, USA
| | - Hamid Prasa
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu city, 600 Cebu, Philippines
| | - Vahid Fallah Omrani
- Department of Biological Sciences, University of Calgary, Calgary, AB T2N 1N4, Canada
| | - Ali Rostami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
| |
Collapse
|
|
5
|
Malli C, Pandit L, D’Cunha A, Sudhir A. Helicobacter pylori infection may influence prevalence and disease course in myelin oligodendrocyte glycoprotein antibody associated disorder (MOGAD) similar to MS but not AQP4-IgG associated NMOSD. Front Immunol 2023; 14:1162248. [PMID: 37304259 PMCID: PMC10250711 DOI: 10.3389/fimmu.2023.1162248] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/09/2023] [Accepted: 03/30/2023] [Indexed: 06/13/2023] Open
Abstract
Background Helicobacter pylori (Hp) persists after colonizing the gut in childhood, and potentially regulates host immune system through this process. Earlier studies have shown that Hp infection in childhood, may protect against MS in later life. Such an association was not seen with AQP4-IgG positive NMOSD, while the association with MOGAD is unclear. Objective To evaluate frequency of Hp IgG among patients with MOGAD, MS, NMOSD and matched controls and its effect on disease course. To ascertain whether childhood socio economic factors were linked to prevalence of Hp infection. Methods In all, 99 patients diagnosed to have MOGAD, 99 AQP4 IgG+ NMOSD, 254MS and 243 matched controls were included. Patient demographics, diagnosis, age at disease onset, duration and the last recorded expanded disability status scale (EDSS) were obtained from our records. Socioeconomic and educational status was queried using a previously validated questionnaire. Serum HpIgG was detected using ELISA kits (Vircell, Spain). Result Frequency of Hp IgG was significantly lower among MOGAD (28.3% vs 44%, p-0.007) and MS (21.2% vs 44%, p-0.0001) but not AQP4-IgG+ NMOSD patients (42.4% vs 44%, p-0.78) when compared to controls. Frequency of Hp IgG in MOGAD & MS patients combined (MOGAD-MS) was significantly lower than those with NMOSD (23.2% vs 42.4%, p- 0.0001). Seropositive patients with MOGAD- MS were older (p-0.001. OR -1.04, 95% CI- 1.01- 1.06) and had longer disease duration (p- 0.04, OR- 1.04, 95% CI- 1.002- 1.08) at time of testing. Educational status was lower among parents/caregivers of this study cohort (p- 0.001, OR -2.34, 95% CI- 1.48-3.69) who were Hp IgG+. Conclusions In developing countries Hp infection may be a significant environmental factor related to autoimmune demyelinating CNS disease. Our preliminary data suggests that Hp may exert a differential influence - a largely protective role for MS-MOGAD but not NMOSD and may influence disease onset and course. This differential response maybe related to immuno-pathological similarities between MOGAD and MS in contrast to NMOSD. Our study further underscores the role of Hp as a surrogate marker for poor gut hygiene in childhood and its association with later onset of autoimmune diseases.
Collapse
|
|
6
|
Arjmandi D, Abdollahi A, Ardekani A, Razavian I, Razavian E, Sartip B, Mahjour S, Parsa H, Kyvanani NA, Marhoommirzabak E, Kountouras J, Rostami A. Helicobacter pylori infection and risk of multiple sclerosis: An updated meta-analysis. Helicobacter 2022; 27:e12927. [PMID: 36046943 DOI: 10.1111/hel.12927] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/18/2022] [Revised: 08/14/2022] [Accepted: 08/19/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND There is considerable controversy around the question as to whether Helicobacter pylori (H. pylori) infection has a protective or causative role in the development of multiple sclerosis (MS). This study evaluated published information to assess the association between H. pylori infection and MS. METHODS We conducted a comprehensive systematic review of relevant observational studies in international databases. A random-effects model was used to calculate pooled odds ratio (OR) and 95% confidence interval (CI). I2 statistic was used to assess the between-study heterogeneity. Subgroup and meta-regression analyses were applied to identify the source of heterogeneity. RESULTS In total, 22 studies (25 datasets) were eligible for the meta-analysis: 17 datasets had prevalence data and eight datasets had data on the mean titer of anti-H. pylori IgG. The pooled prevalence of H. pylori was 44.1% (908/2606) in the MS patients and 46.1% (1016/2200) in the controls, indicating a non-significant protective effect of H. pylori on MS (OR, 0.82; 95%CI, 0.58-1.17). In the subgroup analysis, studies that used ELISA yielded a significant protective association (OR, 0.59; 95%CI, 0.46-0.77), while a positive non-significant association (OR, 1.33; 95%CI, 0.83-2.15) was found from studies that used other serological methods; interestingly, a significant positive association (OR, 6.64; 95%CI, 2.40-13.76) was found from studies that used histological methods to detect H. pylori infection. CONCLUSIONS Our findings do not support the hypothesis that H. pylori infection represents a protective factor against the development of MS; however, the results varied depending on the diagnostic method(s). Particularly, a significant positive association was identified when studies introduced results based on histological examination, suggesting that active H. pylori infection might be a risk factor for development of MS. Thus, further studies are needed utilizing accurate diagnostic methods to elucidate the association between active H. pylori infection and MS.
Collapse
Affiliation(s)
- Delaram Arjmandi
- Immunoregulation Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| | - Ali Abdollahi
- Department of Surgery, Faculty of Medicine, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran
| | - Ali Ardekani
- School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Iman Razavian
- Department of Neurosurgery, Functional Neurosurgery Research Center, Shohada Tajrish Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
| | - Elnaz Razavian
- Department of Neurology, Tehran Medical Sciences Branch, Islamic Azad University, Tehran, Iran
| | - Behnam Sartip
- Department of Internal Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
| | - Sanaz Mahjour
- Department of Psychiatry and Behavioral Sciences, Northwestern Feinberg School of Medicine, Chicago, Illinois, USA
| | - Hamid Parsa
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu City, Philippines
| | - Nastaran Azizi Kyvanani
- Independent Researcher in the Field of Microbiology and Infectious Diseases, Erfurt, Germany
| | - Elika Marhoommirzabak
- Department of Neurology, University of Visayas, Gullas College of Medicine, Cebu City, Philippines
| | - Jannis Kountouras
- Second Medical Clinic, School of Medicine, Ippokration Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
| | - Ali Rostami
- Infectious Diseases and Tropical Medicine Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran
| |
Collapse
|
|
7
|
Park AM, Tsunoda I. Helicobacter pylori infection in the stomach induces neuroinflammation: the potential roles of bacterial outer membrane vesicles in an animal model of Alzheimer's disease. Inflamm Regen 2022; 42:39. [PMID: 36058998 PMCID: PMC9442937 DOI: 10.1186/s41232-022-00224-8] [Citation(s) in RCA: 40] [Impact Index Per Article: 13.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2022] [Accepted: 08/09/2022] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (HP) is a Gram-negative bacterium that colonizes the human stomach chronically. Colonization of HP in the gastric mucosa not only causes gastrointestinal diseases, but also is associated with extra-gastric diseases, such as idiopathic thrombocytopenic purpura and neurological diseases. Among neurological diseases, epidemiological studies have shown that HP infection increases the prevalence of Alzheimer's disease (AD) and Parkinson's disease (PD). Since HP does not invade the central nervous system (CNS), it has been considered that systemic immunological changes induced by HP infection may play pathogenic roles in AD and PD. Here, we investigated the effects of HP infection on the CNS in vivo and in vitro. In the CNS, chronically HP-infected mice had microglial activation without HP colonization, although systemic immunological changes were not observed. This led us to explore the possibility that HP-derived outer membrane vesicles (HP-OMVs) could cause neuroinflammation. OMVs are small, spherical bilayer vesicles (20-500 nm) released into the extracellular space from the outer membrane of Gram-negative bacteria; OMVs contain lipopolysaccharide, proteins, peptidoglycan, DNA, and RNA. OMVs have also been shown to activate both innate and acquired immune cells in vitro, and to disrupt the tight junctions of the gastric epithelium ("leaky gut") as well as cross the blood-brain barrier in vivo. Thus, in theory, OMVs can activate immune responses in the remote organs, including the lymphoid organs and CNS, if only OMVs enter the systemic circulation. From the exosome fraction of sera from HP-infected mice, we detected HP-specific DNA, suggesting the presence of HP-OMVs. We also found that microglia incubated with HP-OMVs in vitro increased the cell proliferation, inflammatory cytokine production, and migration. On the other hand, HP-OMVs suppressed the cell proliferation of neuroblastoma in vitro. Lastly, we found that AD model mice infected with HP had amyloid plaques adjacent to activated microglia and astrocytes in vivo. Based on the literature review and our experimental data, we propose our working hypothesis that OMVs produced in chronic HP infection in the gut induce neuroinflammation in the CNS, explaining the higher prevalence of AD in HP-infected people.
Collapse
Affiliation(s)
- Ah-Mee Park
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan.
| | - Ikuo Tsunoda
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka, 589-8511, Japan
| |
Collapse
|
|
8
|
Mărginean CD, Mărginean CO, Meliț LE. Helicobacter pylori-Related Extraintestinal Manifestations—Myth or Reality. CHILDREN 2022; 9:children9091352. [PMID: 36138661 PMCID: PMC9497822 DOI: 10.3390/children9091352] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Revised: 08/29/2022] [Accepted: 09/01/2022] [Indexed: 11/16/2022]
Abstract
It is well documented that Helicobacter pylori (H. pylori) can cause both gastrointestinal and extraintestinal manifestations. The latter one represents a major burden in terms of diagnosis and treatment. H. pylori-associated systemic subclinical inflammation is mostly responsible for the development of extraintestinal manifestations, and its early eradication might result in preventing all adverse events related to their occurrence. Thus, it was suggested that H. pylori might be associated with iron deficiency anemia, thrombocytopenia (immune thrombocytopenic purpura), Schonlein Henoch purpura, failure to thrive, vitamin B12 deficiency, diabetes mellitus, body mass index, cardiovascular diseases, as well as certain neurological conditions. Nevertheless, studies showed both pros and cons in terms of the role of H. pylori in the development of previously mentioned clinical entity underlining the crucial need for further studies on these topics. Although most of these extraintestinal manifestations occur during adulthood, we must not forget that H. pylori infection is acquired mainly during childhood, and thus its early diagnosis and eradication might represent the cornerstone in the prevention of H. pylori-induced inflammatory status and consequently of all related extraintestinal conditions.
Collapse
Affiliation(s)
- Cristian Dan Mărginean
- Department of Pediatrics I, County Emergency Hospital Târgu Mureș, Gheorghe Marinescu Street No. 50, 540136 Târgu Mureș, Romania
| | - Cristina Oana Mărginean
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
- Correspondence:
| | - Lorena Elena Meliț
- Department of Pediatrics I, “George Emil Palade” University of Medicine, Pharmacy, Science, and Technology of Târgu Mureș, Gheorghe Marinescu Street No. 38, 540136 Târgu Mureș, Romania
| |
Collapse
|
|
9
|
He J, Liu Y, Ouyang Q, Li R, Li J, Chen W, Hu W, He L, Bao Q, Li P, Hu C. Helicobacter pylori and unignorable extragastric diseases: Mechanism and implications. Front Microbiol 2022; 13:972777. [PMID: 35992650 PMCID: PMC9386483 DOI: 10.3389/fmicb.2022.972777] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2022] [Accepted: 07/11/2022] [Indexed: 11/15/2022] Open
Abstract
Considered as the most popular pathogen worldwide, Helicobacter pylori is intensively associated with diverse gastric diseases, including gastric ulcers, chronic progressive gastritis, and gastric cancer. Aside from its pathogenic effect on gastric diseases, growing evidences reveal that H. pylori may be related to numerous extragastric diseases. In this article, we reviewed recent studies and systematically elucidated that H. pylori may interfere with many biological processes outside the stomach and influence the occurrence of various extragastric diseases. Many epidemiological studies have indicated that H. pylori plays a pathogenic role in COVID-19, atherosclerosis, hyperemesis gravidarum and several other extragastric diseases, while the effect of H. pylori is currently under investigation in gastroesophageal reflux disease, asthma, and inflammatory bowel disease. Moreover, we also summarized the possible pathogenic mechanisms of H. pylori that may be related to chronic systemic inflammation and molecular mimicker. Taken together, this review provides a new perspective on the role of H. pylori in extragastric diseases and explores the possible mechanisms, which may help guide clinical treatment.
Collapse
Affiliation(s)
- Junjian He
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Yunyi Liu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Qin Ouyang
- Department of Medicinal Chemistry, College of Pharmacy, Army Medical University, Chongqing, China
| | - Rongxing Li
- Department of Foreign Languages, Army Medical University, Chongqing, China
| | - Jie Li
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Weiyan Chen
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Weichao Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Lijiao He
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Qiyu Bao
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
| | - Ping Li
- Institute of Cardiovascular Diseases, Xinqiao Hospital, Army Medical University, Chongqing, China
- *Correspondence: Ping Li,
| | - Changjiang Hu
- Department of Gastroenterology, Xinqiao Hospital, Army Medical University, Chongqing, China
- Changjiang Hu,
| |
Collapse
|
|
10
|
Szilagyi A. Relationships between Western Non Communicable Diseases and Geographic Pattern Modifiers Based on Latitude and Lactase Distributions. Med Hypotheses 2022. [DOI: 10.1016/j.mehy.2022.110797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|
|
11
|
Sarsenbaeva AS. <i>Helicobacter pylori</i>-associated comorbidity. EXPERIMENTAL AND CLINICAL GASTROENTEROLOGY 2021:38-52. [DOI: 10.31146/1682-8658-ecg-193-9-38-52] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
Abstract
Helicobacter pylori (H. pylori) infection is known to lead to various diseases such as gastric and duodenal ulcers, chronic gastritis and malignant diseases, including MALT lymphoma and stomach cancer. To date, various factors of pathogenicity and virulence of the H. pylori bacterium have been studied. The interaction of infection with host cells leads to the induction of inflammatory responses through the release of cytokines, activation of apoptosis or proliferation, which leads to inflammation and dysfunction of the epithelial barrier. This process can facilitate the movement of H. pylori virulence factors and inflammatory mediators into the bloodstream and promote or enhance the development of a systemic inflammatory response and the possible clinical effects of H. pylori infections outside the stomach. The purpose of this review is to clarify the available data on H. pylori-associated comorbidity with diseases of the cardiovascular, nervous, endocrine systems, autoimmune diseases and some other pathologies outside the digestive system.
Collapse
Affiliation(s)
- A. S. Sarsenbaeva
- South Ural State Medical University of the Ministry of Health of the Russian Federation
| |
Collapse
|
|
12
|
Schroeter CB, Huntemann N, Bock S, Nelke C, Kremer D, Pfeffer K, Meuth SG, Ruck T. Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells. Front Immunol 2021; 12:747143. [PMID: 34691057 PMCID: PMC8529161 DOI: 10.3389/fimmu.2021.747143] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2021] [Accepted: 09/20/2021] [Indexed: 12/22/2022] Open
Abstract
Regulatory T cells (Tregs) are the major determinant of peripheral immune tolerance. Many Treg subsets have been described, however thymus-derived and peripherally induced Tregs remain the most important subpopulations. In multiple sclerosis, a prototypical autoimmune disorder of the central nervous system, Treg dysfunction is a pathogenic hallmark. In contrast, induction of Treg proliferation and enhancement of their function are central immune evasion mechanisms of infectious pathogens. In accordance, Treg expansion is compartmentalized to tissues with high viral replication and prolonged in chronic infections. In friend retrovirus infection, Treg expansion is mainly based on excessive interleukin-2 production by infected effector T cells. Moreover, pathogens seem also to enhance Treg functions as shown in human immunodeficiency virus infection, where Tregs express higher levels of effector molecules such as cytotoxic T-lymphocyte-associated protein 4, CD39 and cAMP and show increased suppressive capacity. Thus, insights into the molecular mechanisms by which intracellular pathogens alter Treg functions might aid to find new therapeutic approaches to target central nervous system autoimmunity. In this review, we summarize the current knowledge of the role of pathogens for Treg function in the context of autoimmune neuroinflammation. We discuss the mechanistic implications for future therapies and provide an outlook for new research directions.
Collapse
Affiliation(s)
- Christina B Schroeter
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Niklas Huntemann
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Stefanie Bock
- Department of Neurology With Institute of Translational Neurology, University of Münster, Münster, Germany
| | - Christopher Nelke
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - David Kremer
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Klaus Pfeffer
- Institute of Medical Microbiology and Hospital Hygiene, Heinrich-Heine-University Düsseldorf, Düsseldorf, Germany
| | - Sven G Meuth
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| | - Tobias Ruck
- Department of Neurology, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany
| |
Collapse
|
|
13
|
Zarghami A, Li Y, Claflin SB, van der Mei I, Taylor BV. Role of environmental factors in multiple sclerosis. Expert Rev Neurother 2021; 21:1389-1408. [PMID: 34494502 DOI: 10.1080/14737175.2021.1978843] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/22/2023]
Abstract
INTRODUCTION Environmental factors play a significant role in the pathogenesis and progression of multiple sclerosis (MS), either acting alone or by interacting with other environmental or genetic factors. This cumulative exposure to external risk factors is highly complex and highly variable between individuals. AREAS COVERED We narratively review the current evidence on the role of environment-specific risk factors in MS onset and progression, as well as the effect of gene-environment interactions and the timing of exposure We have reviewed the latest literature, by Ovid Medline, retrieving the most recently published systematic reviews and/or meta-analyses and more recent studies not previously included in meta-analyses or systematic reviews. EXPERT OPINION There is some good evidence supporting the impact of some environmental risk factors in increasing the risk of developing MS. Tobacco smoking, low vitamin D levels and/or low sun exposure, Epstein Barr Virus (EBV) seropositivity and a history of infectious mononucleosis may increase the risk of developing MS. Additionally, there is some evidence that gene-smoking, gene-EBV, and smoking-EBV interactions additively affect the risk of MS onset. However, the evidence for a role of other environmental factors in MS progression is limited. Finally, there is some evidence that tobacco smoking, insufficient vitamin D levels and/or sun exposure have impacts on MS phenotypes and various markers of disease activity including relapse, disability progression and MRI findings. Clearly the effect of environmental factors on MS disease course is an area that requires significantly more research.
Collapse
Affiliation(s)
- Amin Zarghami
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Ying Li
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Suzi B Claflin
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Ingrid van der Mei
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| | - Bruce V Taylor
- Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS, Australia
| |
Collapse
|
|
14
|
Papeix C, Donze C, Lebrun-Frénay C. Infections and multiple sclerosis: Recommendations from the French Multiple Sclerosis Society. Rev Neurol (Paris) 2021; 177:980-994. [PMID: 34303537 DOI: 10.1016/j.neurol.2021.04.011] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/22/2021] [Accepted: 04/29/2021] [Indexed: 01/03/2023]
Abstract
INTRODUCTION Viral, bacterial, or fungal infections are suspected of triggering multiple sclerosis (MS) and promoting relapses of the disease and are likely to be promoted by immune-active treatments. This raises questions about the infectious workup and preventive treatment of these infections prior to their initiation. OBJECTIVES To establish recommendations on infections and MS. Provide information to patients and healthcare professionals on the minimal infectious workup to be performed in an MS patient at diagnosis and prior to initiation of immuno-active therapy in MS. METHODS The recommendation attempts to answer four main questions about infections and MS. The French Group for Recommendations in Multiple Sclerosis (France4MS) did a systematic review of articles from PubMed and universities databases (from January 1975 to June 2020), using the RAND/UCLA formalized consensus method. The RAND/UCLA method has been developed to synthesize the scientific literature and expert opinions on health care topics and was used for reaching a formal agreement. Twenty-three experts contributed to the detailed review and a group of 63 multidisciplinary health professionals validated the final version of 36 recommendations. RESULTS It is recommended that MS patients undergo a minimal infectious workup, check their vaccination status at diagnosis, and repeat it during follow-up and before starting immunotherapy. Screening and preventive treatment of viral (group Herpes virus, HPV, JCV, HCV, HBV), bacterial (mycobacteria) and fungal (Cryptococcus) infections is recommended prior to the initiation of certain immuno-active MS therapies. DISCUSSION AND CONCLUSIONS At diagnosis of MS and prior to the choice of therapeutic strategy, it is recommended to update the vaccination schedule of MS patients in reference to the HCSP vaccination schedule and the SFSEP recommendations. Before starting immunosuppressive treatment, it is recommended to inform patients of the risks of infections and to look for a constitutive or acquired immune deficiency. Health professionals and patients should be informed of the updated recommendations on infections and MS.
Collapse
Affiliation(s)
- C Papeix
- Département de neurologie, CRCSEP-Paris, Sorbonne Université, Hôpital de la Pitié salpêtrière, AP-HP 6, Paris 75013, France.
| | - C Donze
- Faculté de médecine et de maïeutique de Lille, hôpital Saint-Philibert, groupement des hôpitaux de l'institut catholique de Lille, Lomme, France
| | - C Lebrun-Frénay
- URC2A, Cote d'Azur University, CRCSEP-Côte d'Azur, neurologie, Hôpital Pasteur2, CHU Nice, France
| | | | | | | | | | | | | |
Collapse
|
|
15
|
Farmen K, Tofiño-Vian M, Iovino F. Neuronal Damage and Neuroinflammation, a Bridge Between Bacterial Meningitis and Neurodegenerative Diseases. Front Cell Neurosci 2021; 15:680858. [PMID: 34149363 PMCID: PMC8209290 DOI: 10.3389/fncel.2021.680858] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Accepted: 05/03/2021] [Indexed: 12/13/2022] Open
Abstract
Bacterial meningitis is an inflammation of the meninges which covers and protects the brain and the spinal cord. Such inflammation is mostly caused by blood-borne bacteria that cross the blood-brain barrier (BBB) and finally invade the brain parenchyma. Pathogens such as Streptococcus pneumoniae, Neisseria meningitidis, and Haemophilus influenzae are the main etiological causes of bacterial meningitis. After trafficking across the BBB, bacterial pathogens in the brain interact with neurons, the fundamental units of Central Nervous System, and other types of glial cells. Although the specific molecular mechanism behind the interaction between such pathogens with neurons is still under investigation, it is clear that bacterial interaction with neurons and neuroinflammatory responses within the brain leads to neuronal cell death. Furthermore, clinical studies have shown indications of meningitis-caused dementia; and a variety of neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease and Huntington's disease are characterized by the loss of neurons, which, unlike many other eukaryotic cells, once dead or damaged, they are seldom replaced. The aim of this review article is to provide an overview of the knowledge on how bacterial pathogens in the brain damage neurons through direct and indirect interactions, and how the neuronal damage caused by bacterial pathogen can, in the long-term, influence the onset of neurodegenerative disorders.
Collapse
Affiliation(s)
| | | | - Federico Iovino
- Department of Neuroscience, Karolinska Institutet Biomedicum, Stockholm, Sweden
| |
Collapse
|
|
16
|
Youssefi M, Tafaghodi M, Farsiani H, Ghazvini K, Keikha M. Helicobacter pylori infection and autoimmune diseases; Is there an association with systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis and autoimmune pancreatitis? A systematic review and meta-analysis study. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2021; 54:359-369. [PMID: 32891538 DOI: 10.1016/j.jmii.2020.08.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 8.8] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 03/21/2020] [Revised: 07/07/2020] [Accepted: 08/16/2020] [Indexed: 02/05/2023]
Affiliation(s)
- Masoud Youssefi
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Mohsen Tafaghodi
- School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran; Nanotechnology Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hadi Farsiani
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Kiarash Ghazvini
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Masoud Keikha
- Antimicrobial Resistance Research Center, Mashhad University of Medical Sciences, Mashhad, Iran; Department of Microbiology and Virology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran; Student Research Committee, Mashhad University of Medical Sciences, Mashhad, Iran.
| |
Collapse
|
|
17
|
Murdaca G, Greco M, Borro M, Gangemi S. Hygiene hypothesis and autoimmune diseases: A narrative review of clinical evidences and mechanisms. Autoimmun Rev 2021; 20:102845. [PMID: 33971339 DOI: 10.1016/j.autrev.2021.102845] [Citation(s) in RCA: 31] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Revised: 02/20/2021] [Accepted: 02/27/2021] [Indexed: 12/12/2022]
Abstract
Since the start of the "modern era", characterized by the increase in urbanization, a progressive attention to hygiene and autoimmune conditions has considerably grown. Although these diseases are often multifactorial, it was demonstrated that environment factors such as pollution, diet and lifestyles may play a crucial role together with genetic signature. Our research, based on the newest and most significant literature of this topic, highlights that the progressive depletion of microbes and parasites due to increased socioeconomic improvement, may lead to a derangement of immunoregulatory mechanisms. Moreover, special attention was given to the complex interplay between microbial agents, as gut microbiome, diet and vitamin D supplementation with the aim of identifying promising future therapeutic options. In conclusion, autoimmunity cannot be limited to hygiene-hypothesis, but from the point of view of precision medicine, this theory represents a fundamental element together with the study of genomics, the microbiome and proteomics, in order to understand the complex functioning of the immune system.
Collapse
Affiliation(s)
- Giuseppe Murdaca
- Department of Internal Medicine, University of Genoa and IRCCS Ospedale Policlinico San Martino, Genoa, Italy.
| | - Monica Greco
- Internal Medicine Department, San Paolo Hospital, 17100 Savona, Italy
| | - Matteo Borro
- Internal Medicine Department, San Paolo Hospital, 17100 Savona, Italy
| | - Sebastiano Gangemi
- School and Operative Unit of Allergy and Clinical Immunology, Department of Clinical and Experimental Medicine, University of Messina, 98125 Messina, Italy
| |
Collapse
|
|
18
|
Cerri G, Farina M, Brundu A, Gavini E, Salis A, Dathe W. Antibacterial activity of Zn-loaded Cuban zeolite against Helicobacter pylori in comparison to its Na-loaded and unmodified counterparts. ENVIRONMENTAL GEOCHEMISTRY AND HEALTH 2021; 43:2037-2048. [PMID: 33244649 PMCID: PMC8081705 DOI: 10.1007/s10653-020-00781-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 04/10/2020] [Accepted: 11/10/2020] [Indexed: 05/02/2023]
Abstract
Helicobacter pylori can be found in the stomach of about half of the humans, and a large population can be associated with serious diseases. To survive in the stomach H. pylori increases the pH locally by producing ammonia which binds to H+ becoming ammonium. This work investigated the effects on the in-vitro growth of H. pylori of a natural cation-exchanger mainly composed (≈70%) of clinoptilolite and mordenite. The zeolitized material from Cuba was evaluated in its original form (M), as well as in its Na- (M-Na) and Zn-exchanged (M-Zn) counterparts. In the preliminary agar cup diffusion test, H. pylori revealed susceptibility only to M-Zn, with a direct relationship between concentration and width of inhibition halo. Further experiments evidenced that bacterium replication increases when ammonium is supplied to the growth medium and decreases when zeolites subtract NH4+ via ion exchange. Due to the multi-cationic population of its zeolites M was not effective enough in removing ammonium and, in the Minimum Inhibitory Concentration (MIC) test, allowed bacterial growth even at a concentration of 50 mg/mL. Inhibition was achieved with M-Na because it contained sodium zeolites capable of maximizing NH4+ subtraction, although the MIC was high (30 mg/mL). M-Zn evidenced a more effective inhibitory capacity, with a MIC of 4 mg/mL. Zinc has antimicrobial properties and H. pylori growth was affected by Zn2+ released from clinoptilolite and mordenite. These zeolites, being more selective towards NH4+ than Zn2+, can also subtract ammonium to the bacterium, thus enhancing the efficacy of M-Zn.
Collapse
Affiliation(s)
- Guido Cerri
- Department of Architecture, Design and Urban Planning - GeoMaterials Lab, Sassari University, Via Piandanna 4, 07100, Sassari, Italy.
| | - Mauro Farina
- Department of Architecture, Design and Urban Planning - GeoMaterials Lab, Sassari University, Via Piandanna 4, 07100, Sassari, Italy
| | - Antonio Brundu
- Department of Architecture, Design and Urban Planning - GeoMaterials Lab, Sassari University, Via Piandanna 4, 07100, Sassari, Italy
| | - Elisabetta Gavini
- Department of Chemistry and Pharmacy, Sassari University, Via Muroni 23, 07100, Sassari, Italy
| | - Andrea Salis
- Department of Chemistry and Pharmacy, Sassari University, Via Muroni 23, 07100, Sassari, Italy
| | - Wilfried Dathe
- Heck Bio-Pharma GmbH, Gerberstraße 15, 73650, Winterbach, Germany
| |
Collapse
|
|
19
|
Santos MLC, de Brito BB, da Silva FAF, Sampaio MM, Marques HS, Oliveira e Silva N, de Magalhães Queiroz DM, de Melo FF. Helicobacter pylori infection: Beyond gastric manifestations. World J Gastroenterol 2020; 26:4076-4093. [PMID: 32821071 PMCID: PMC7403793 DOI: 10.3748/wjg.v26.i28.4076] [Citation(s) in RCA: 79] [Impact Index Per Article: 15.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2020] [Revised: 05/29/2020] [Accepted: 07/14/2020] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is a bacterium that infects more than a half of world’s population. Although it is mainly related to the development of gastroduodenal diseases, several studies have shown that such infection may also influence the development and severity of various extragastric diseases. According to the current evidence, whereas this bacterium is a risk factor for some of these manifestations, it might play a protective role in other pathological conditions. In that context, when considered the gastrointestinal tract, H. pylori positivity have been related to Inflammatory Bowel Disease, Gastroesophageal Reflux Disease, Non-Alcoholic Fatty Liver Disease, Hepatic Carcinoma, Cholelithiasis, and Cholecystitis. Moreover, lower serum levels of iron and vitamin B12 have been found in patients with H. pylori infection, leading to the emergence of anemias in a portion of them. With regards to neurological manifestations, a growing number of studies have associated that bacterium with multiple sclerosis, Alzheimer’s disease, Parkinson’s disease, and Guillain-Barré syndrome. Interestingly, the risk of developing cardiovascular disorders, such as atherosclerosis, is also influenced by the infection. Besides that, the H. pylori-associated inflammation may also lead to increased insulin resistance, leading to a higher risk of diabetes mellitus among infected individuals. Finally, the occurrence of dermatological and ophthalmic disorders have also been related to that microorganism. In this sense, this minireview aims to gather the main studies associating H. pylori infection with extragastric conditions, and also to explore the main mechanisms that may explain the role of H. pylori in those diseases.
Collapse
Affiliation(s)
- Maria Luísa Cordeiro Santos
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Breno Bittencourt de Brito
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Mariana Miranda Sampaio
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | | | - Natália Oliveira e Silva
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| | - Dulciene Maria de Magalhães Queiroz
- Laboratory of Research in Bacteriology, Faculdade de Medicina, Universidade Federal de Minas Gerais, Belo Horizonte 30130-100, Minas Gerais, Brazil
| | - Fabrício Freire de Melo
- Instituto Multidisciplinar em Saúde, Universidade Federal da Bahia, Vitória da Conquista 45029-094, Bahia, Brazil
| |
Collapse
|
|
20
|
Cavallo S. Immune-mediated genesis of multiple sclerosis. J Transl Autoimmun 2020; 3:100039. [PMID: 32743522 PMCID: PMC7388381 DOI: 10.1016/j.jtauto.2020.100039] [Citation(s) in RCA: 22] [Impact Index Per Article: 4.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/08/2019] [Revised: 01/03/2020] [Accepted: 01/05/2020] [Indexed: 12/14/2022] Open
Abstract
Multiple sclerosis (MS) is widely acknowledged to be an autoimmune disease affecting the neuronal myelin structure of the CNS. Autoantigens recognized as the target of this autoimmune process are: myelin basal protein, anti-proteolipid protein, antimyelin-associated glycoprotein and antimyelin-based oligodendrocytic basic protein. Ample evidence supports the idea of a dysregulation of immunological tolerance towards self-antigens of neuronal myelin structure triggered by one or more viral or bacterial microbial agents in predisposed HLA gene subjects. Genetic predisposition to MS has been highlighted by numerous studies associating the disease to specific HLA haplotypes. Moreover, a wide range of evidence supports the fact that MS may be consequence of one or more viral or bacterial infections such as measles virus, EBV, HHV6, HZV, Chlamydia pneumoniae, Helicobacter Pylori, and other microbial agents. Microbiota elements also seems to have a role on the determinism of the disease as a pathogenic or protective factor. The autoimmune pathogenetic process could arise when a molecular mimicry between a foreign microbial antigen and an auto-antigen occurs in an HLA gene subject competent for that particular antigen. The antigen-presenting cells in this case would induce the activation of a specific Th clone causing a cross-reaction between a foreign antigen and an autoantigen resulting in an autoimmune response.
A multifactorial ethiopathogenetic model based on immunomediation is a reliable hypothesis for multiple sclerosis. Evidence found in the scientific literature makes it possible to reconstruct this etiopathogenetic hypothesis for MS. HLA gene predisposition, correlation with infections, molecular mimicry and other immunological data are reported.
Collapse
Affiliation(s)
- Salvatore Cavallo
- Expert Doctor in Non-Conventional Medicine, Professor and Member of the Board of the MMS, MMS (Medicina di Modulazione Dei Sistemi) Roma, Salvatore Cavallo Via G.B. Pergolesi, 28, 75100, Matera, Italy
| |
Collapse
|
|
21
|
Jakimovski D, Weinstock-Guttman B, Ramanathan M, Dwyer MG, Zivadinov R. Infections, Vaccines and Autoimmunity: A Multiple Sclerosis Perspective. Vaccines (Basel) 2020; 8:vaccines8010050. [PMID: 32012815 PMCID: PMC7157658 DOI: 10.3390/vaccines8010050] [Citation(s) in RCA: 35] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Revised: 01/21/2020] [Accepted: 01/24/2020] [Indexed: 12/13/2022] Open
Abstract
Background: Multiple sclerosis (MS) is a chronic neuroinflammatory and neurodegenerative disease that is associated with multiple environmental factors. Among suspected susceptibility events, studies have questioned the potential role of overt viral and bacterial infections, including the Epstein Bar virus (EBV) and human endogenous retroviruses (HERV). Furthermore, the fast development of immunomodulatory therapies further questions the efficacy of the standard immunization policies in MS patients. Topics reviewed: This narrative review will discuss the potential interplay between viral and bacterial infections and their treatment on MS susceptibility and disease progression. In addition, the review specifically discusses the interactions between MS pathophysiology and vaccination for hepatitis B, influenza, human papillomavirus, diphtheria, pertussis, and tetanus (DTP), and Bacillus Calmette-Guerin (BCG). Data regarding potential interaction between MS disease modifying treatment (DMT) and vaccine effectiveness is also reviewed. Moreover, HERV-targeted therapies such as GNbAC1 (temelimab), EBV-based vaccines for treatment of MS, and the current state regarding the development of T-cell and DNA vaccination are discussed. Lastly, a reviewing commentary on the recent 2019 American Academy of Neurology (AAN) practice recommendations regarding immunization and vaccine-preventable infections in the settings of MS is provided. Conclusion: There is currently no sufficient evidence to support associations between standard vaccination policies and increased risk of MS. MS patients treated with immunomodulatory therapies may have a lower benefit from viral and bacterial vaccination. Despite their historical underperformance, new efforts in creating MS-based vaccines are currently ongoing. MS vaccination programs follow the set back and slow recovery which is widely seen in other fields of medicine.
Collapse
Affiliation(s)
- Dejan Jakimovski
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
- Correspondence:
| | - Bianca Weinstock-Guttman
- Jacobs MS Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
| | - Murali Ramanathan
- School of Pharmaceutical Sciences, University at Buffalo, State University of New York, Buffalo, NY 14214, USA
| | - Michael G. Dwyer
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
| | - Robert Zivadinov
- Buffalo Neuroimaging Analysis Center, Department of Neurology, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
- Center for Biomedical Imaging at Clinical Translational Science Institute, University at Buffalo, State University of New York, Buffalo, NY 14203, USA
| |
Collapse
|
|
22
|
Wasko NJ, Nichols F, Clark RB. Multiple sclerosis, the microbiome, TLR2, and the hygiene hypothesis. Autoimmun Rev 2020; 19:102430. [DOI: 10.1016/j.autrev.2019.102430] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2019] [Accepted: 07/11/2019] [Indexed: 12/14/2022]
|
|
23
|
Chaiwiang N, Poyomtip T. Microbial dysbiosis and microbiota-gut-retina axis: The lesson from brain neurodegenerative diseases to primary open-angle glaucoma pathogenesis of autoimmunity. Acta Microbiol Immunol Hung 2019; 66:541-558. [PMID: 31786943 DOI: 10.1556/030.66.2019.038] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022]
Abstract
In recent years, microbiota-associated neurodegenerative diseases have been exploited and provided new insight into disease pathogenesis. However, primary open-angle glaucoma (POAG), known as a complex neurodegenerative disease resulting from retinal ganglion cell death and optic nerve damage, can cause irreversible blindness and visual field loss. POAG, which shares several similarities with Parkinson's disease (PD) and Alzheimer's disease (AD), has limited studies and slow progression in the understanding of pathogenesis when compared to PD and AD. In this review, we summarized the current knowledge of POAG and commensal microbiota, combined with several lines of evidence in PD and AD to propose a possible hypothesis for POAG pathogenesis: microorganisms cause glaucoma via gut-retina axis, resulting in autoantibodies and autoreactive T cells that lead to autoimmunity. Furthermore, dual-hit hypothesis, an example of a commensal pathogen that causes PD, was partially exported in POAG. Finally, future perspectives are suggested to expand understanding of POAG.
Collapse
Affiliation(s)
| | - Teera Poyomtip
- 1 Faculty of Optometry, Ramkhamhaeng University, Bangkok, Thailand
| |
Collapse
|
|
24
|
Ranjbar R, Karampoor S, Jalilian FA. The protective effect of Helicobacter Pylori infection on the susceptibility of multiple sclerosis. J Neuroimmunol 2019; 337:577069. [DOI: 10.1016/j.jneuroim.2019.577069] [Citation(s) in RCA: 16] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/19/2019] [Revised: 09/13/2019] [Accepted: 09/13/2019] [Indexed: 12/18/2022]
|
|
25
|
Domínguez-Andrés J, Netea MG. Impact of Historic Migrations and Evolutionary Processes on Human Immunity. Trends Immunol 2019; 40:1105-1119. [PMID: 31786023 PMCID: PMC7106516 DOI: 10.1016/j.it.2019.10.001] [Citation(s) in RCA: 36] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2019] [Revised: 10/04/2019] [Accepted: 10/09/2019] [Indexed: 12/30/2022]
Abstract
The evolution of mankind has constantly been influenced by the pathogens encountered. The various populations of modern humans that ventured out of Africa adapted to different environments and faced a large variety of infectious agents, resulting in local adaptations of the immune system for these populations. The functional variation of immune genes as a result of evolution is relevant in the responses against infection, as well as in the emergence of autoimmune and inflammatory diseases observed in modern populations. Understanding how host-pathogen interactions have influenced the human immune system from an evolutionary perspective might contribute to unveiling the causes behind different immune-mediated disorders and promote the development of new strategies to detect and control such diseases.
Collapse
Affiliation(s)
- Jorge Domínguez-Andrés
- Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB Nijmegen, The Netherlands.
| | - Mihai G Netea
- Department of Internal Medicine and Radboud Center for Infectious diseases (RCI), Radboud University Nijmegen Medical Centre, Geert Grooteplein 8, 6500HB Nijmegen, The Netherlands; Department for Genomics and Immunoregulation, Life and Medical Sciences Institute (LIMES), University of Bonn, 53115 Bonn, Germany; Human Genomics Laboratory, Craiova University of Medicine and Pharmacy, Craiova, Romania
| |
Collapse
|
|
26
|
Patrick KL, Bell SL, Weindel CG, Watson RO. Exploring the "Multiple-Hit Hypothesis" of Neurodegenerative Disease: Bacterial Infection Comes Up to Bat. Front Cell Infect Microbiol 2019; 9:138. [PMID: 31192157 PMCID: PMC6546885 DOI: 10.3389/fcimb.2019.00138] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2019] [Accepted: 04/16/2019] [Indexed: 12/23/2022] Open
Abstract
Despite major strides in personalized genomics, it remains poorly understood why neurodegenerative diseases occur in only a fraction of individuals with a genetic predisposition and conversely, why individuals with no genetic risk of a disorder develop one. Chronic diseases like Alzheimer's, Parkinson's, and Multiple sclerosis are speculated to result from a combination of genetic and environmental factors, a concept commonly referred to as the “multiple hit hypothesis.” A number of bacterial infections have been linked to increased risk of neurodegeneration, and in some cases, clearance of bacterial pathogens has been correlated with amelioration of central nervous system (CNS) deficits. Additionally, mutations in several genes known to contribute to CNS disorders like Parkinson's Disease have repeatedly been implicated in susceptibility to intracellular bacterial infection. Recent data has begun to demonstrate roles for these genes (PARK2, PINK1, and LRRK2) in modulating innate immune outcomes, suggesting that immune dysregulation may play an even more important role in neurodegeneration than previously appreciated. This review will broadly explore the connections between bacterial infection, immune dysregulation, and CNS disorders. Understanding this interplay and how bacterial pathogenesis contributes to the “multiple-hit hypothesis” of neurodegeneration will be crucial to develop therapeutics to effectively treat both neurodegeneration and infection.
Collapse
Affiliation(s)
- Kristin L Patrick
- Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX, United States
| | - Samantha L Bell
- Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX, United States
| | - Chi G Weindel
- Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX, United States
| | - Robert O Watson
- Department of Microbial Pathogenesis and Immunology, Texas A&M Health Science Center, Bryan, TX, United States
| |
Collapse
|
|
27
|
Kira JI, Isobe N. Helicobacter pylori infection and demyelinating disease of the central nervous system. J Neuroimmunol 2019; 329:14-19. [DOI: 10.1016/j.jneuroim.2018.06.017] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/05/2018] [Accepted: 06/28/2018] [Indexed: 12/29/2022]
|
|
28
|
Cossu D, Yokoyama K, Hattori N. Bacteria-Host Interactions in Multiple Sclerosis. Front Microbiol 2018; 9:2966. [PMID: 30564215 PMCID: PMC6288311 DOI: 10.3389/fmicb.2018.02966] [Citation(s) in RCA: 30] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/01/2018] [Accepted: 11/18/2018] [Indexed: 12/14/2022] Open
Abstract
Multiple sclerosis (MS) is caused by a complex interaction of genetic and environmental factors. Numerous causative factors have been identified that play a role in MS, including exposure to bacteria. Mycobacteria, Chlamydia pneumoniae, Helicobacter pylori, and other bacteria have been proposed as risk factors for MS with different mechanisms of action. Conversely, some pathogens may have a protective effect on its etiology. In terms of acquired immunity, molecular mimicry has been hypothesized as the mechanism by which bacterial structures such as DNA, the cell wall, and intracytoplasmic components can activate autoreactive T cells or produce autoantibodies in certain host genetic backgrounds of susceptible individuals. In innate immunity, Toll-like receptors play an essential role in combating invading bacteria, and their activation leads to the release of cytokines or chemokines that mediate effective adaptive immune responses. These receptors may also be involved in central nervous system autoimmunity, and their contribution depends on the infection site and on the pathogen. We have reviewed the current knowledge of the influence of bacteria on MS development, emphasizing the potential mechanisms of action by which bacteria affect MS initiation and/or progression.
Collapse
Affiliation(s)
- Davide Cossu
- Department of Neurology, Juntendo University, Tokyo, Japan.,Advanced Research Institute for Health Science, Juntendo University, Tokyo, Japan
| | - Kazumasa Yokoyama
- Department of Neurology, Juntendo University, Tokyo, Japan.,Advanced Research Institute for Health Science, Juntendo University, Tokyo, Japan
| | - Nobutaka Hattori
- Department of Neurology, Juntendo University, Tokyo, Japan.,Advanced Research Institute for Health Science, Juntendo University, Tokyo, Japan
| |
Collapse
|
|
29
|
Tiwari S, Lapierre J, Ojha CR, Martins K, Parira T, Dutta RK, Caobi A, Garbinski L, Ceyhan Y, Esteban-Lopez M, El-Hage N. Signaling pathways and therapeutic perspectives related to environmental factors associated with multiple sclerosis. J Neurosci Res 2018; 96:1831-1846. [PMID: 30204260 PMCID: PMC7167107 DOI: 10.1002/jnr.24322] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2018] [Revised: 08/09/2018] [Accepted: 08/13/2018] [Indexed: 12/16/2022]
Abstract
Multiple sclerosis (MS) is an immune-mediated demyelinating disorder of unknown etiology. Both genetic-susceptibility and environment exposures, including vitamin D deficiency, Epstein-Barr viral and Herpesvirus (HHV-6) infections are strongly implicated in the activation of T cells and MS-pathogenesis. Despite precise knowledge of how these factors could be operating alone or in combination to facilitate and aggravate the disease progression, it is clear that prolonged induction of inflammatory molecules and recruitment of other immune cells by the activated T cells results in demyelination and axonal damage. It is imperative to understand the risk factors associated with MS progression and how these factors contribute to disease pathology. Understanding of the underlying mechanisms of what factors triggers activation of T cells to attack myelin antigen are important to strategize therapeutics and therapies against MS. Current review provides a detailed literature to understand the role of both pathogenic and non-pathogenic factors on the impact of MS.
Collapse
Affiliation(s)
- Sneham Tiwari
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Jessica Lapierre
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Chet Raj Ojha
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Kyle Martins
- Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Tiyash Parira
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Rajib Kumar Dutta
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Allen Caobi
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Luis Garbinski
- Cell Biology and Pharmacology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Yasemin Ceyhan
- Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Maria Esteban-Lopez
- Human and Molecular Genetics, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| | - Nazira El-Hage
- Departments of Immunology, Herbert Wertheim College of Medicine, Florida International University, Miami, Florida
| |
Collapse
|
|
30
|
Saberi A, Akhondzadeh S, Kazemi S. Infectious agents and different course of multiple sclerosis: a systematic review. Acta Neurol Belg 2018; 118:361-377. [PMID: 30006858 DOI: 10.1007/s13760-018-0976-y] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2018] [Accepted: 07/05/2018] [Indexed: 01/22/2023]
Abstract
Multiple sclerosis (MS) causes demyelination of white matter of central nervous system and neuro-degeneration due to inflammation. Different types of MS, as well as disease progression, come with different pathology and pathophysiology. The objective of this study was to evaluate the possible association between different micro-organisms and the relapse or progression of MS. Studies indexed in Medline/PMC, Scopus and Web of Science published without time and language limitation until March 2017 were identified through the search terms "infection" or "infectious" and "multiple sclerosis". A total of 20878 abstracts were identified through the initial search terms. Selection of articles and assessment of their quality was done based on Cochrane library guidelines. Full texts were reviewed for 33 articles out of which 14 articles met the criteria for inclusion. Different micro-organisms are known to play roles in the pathogenesis of MS and its relapse; including Human herpesvirus 6 (HHV-6), Human herpesvirus 7 (HHV-7), Epstein-Barr virus (EBV), Chlamydia pneumoniae and Torque teno virus (TTV). But in this review only HHV-6, C. pneumoniae and TTV have been considered to play a role in disease progression in some studies and not all of them. This review concluded that some micro-organisms such as HHV-6, C. pneumoniae and TTV have been considered as cofactors to make MS a progressive type. It should be considered that these findings do not necessarily rule out the role of other pathogens in MS progression but may represent population differences or different sensitivity of the technique used.
Collapse
Affiliation(s)
- Alia Saberi
- Neuroscience Research Center, Department of Neurology, Poursina Hospital, School of Medicine, Guilan University of Medical Sciences, Rasht, Iran
| | - Shahin Akhondzadeh
- Psychiatric Research Center, Roozbeh Hospital, Tehran University of Medical Sciences, Tehran, Iran
| | - Samaneh Kazemi
- Deputy of Research and Technology, Guilan University of Medical Sciences, Rasht, Iran.
| |
Collapse
|
|
31
|
Bravo D, Hoare A, Soto C, Valenzuela MA, Quest AFG. Helicobacter pylori in human health and disease: Mechanisms for local gastric and systemic effects. World J Gastroenterol 2018; 24:3071-3089. [PMID: 30065554 PMCID: PMC6064966 DOI: 10.3748/wjg.v24.i28.3071] [Citation(s) in RCA: 138] [Impact Index Per Article: 19.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2018] [Revised: 05/17/2018] [Accepted: 06/27/2018] [Indexed: 02/06/2023] Open
Abstract
Helicobacter pylori (H. pylori) is present in roughly 50% of the human population worldwide and infection levels reach over 70% in developing countries. The infection has classically been associated with different gastro-intestinal diseases, but also with extra gastric diseases. Despite such associations, the bacterium frequently persists in the human host without inducing disease, and it has been suggested that H. pylori may also play a beneficial role in health. To understand how H. pylori can produce such diverse effects in the human host, several studies have focused on understanding the local and systemic effects triggered by this bacterium. One of the main mechanisms by which H. pylori is thought to damage the host is by inducing local and systemic inflammation. However, more recently, studies are beginning to focus on the effects of H. pylori and its metabolism on the gastric and intestinal microbiome. The objective of this review is to discuss how H. pylori has co-evolved with humans, how H. pylori presence is associated with positive and negative effects in human health and how inflammation and/or changes in the microbiome are associated with the observed outcomes.
Collapse
Affiliation(s)
- Denisse Bravo
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Anilei Hoare
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Cristopher Soto
- Oral Microbiology Laboratory, Pathology and Oral Medicine Department, Faculty of Dentistry, Universidad de Chile, Santiago 8380492, Chile
| | - Manuel A Valenzuela
- Advanced Center for Chronic Diseases, Institute for Health-Related Research and Innovation, Faculty of Health Sciences, Universidad Central de Chile, Santiago 8380447, Chile
| | - Andrew FG Quest
- Advanced Center for Chronic Diseases, Center for Studies on Exercise, Metabolism and Cancer, Biomedical Science Institute, Faculty of Medicine, Universidad de Chile, Santiago 8380447, Chile
| |
Collapse
|
|
32
|
Hossain MJ, Morandi E, Tanasescu R, Frakich N, Caldano M, Onion D, Faraj TA, Erridge C, Gran B. The Soluble Form of Toll-Like Receptor 2 Is Elevated in Serum of Multiple Sclerosis Patients: A Novel Potential Disease Biomarker. Front Immunol 2018; 9:457. [PMID: 29593720 PMCID: PMC5861194 DOI: 10.3389/fimmu.2018.00457] [Citation(s) in RCA: 36] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/21/2017] [Accepted: 02/20/2018] [Indexed: 01/08/2023] Open
Abstract
Multiple sclerosis (MS) is an immune-mediated inflammatory demyelinating disease of the central nervous system. It was previously shown that toll-like receptor (TLR)-2 signaling plays a key role in the murine experimental autoimmune encephalomyelitis (EAE) model of MS, and that TLR2-stimulation of regulatory T cells (Tregs) promotes their conversion to T helper 17 (Th17) cells. Here, we sought potential sources of TLR2 stimulation and evidence of TLR2 activity in MS patient clinical samples. Soluble TLR2 (sTLR2) was found to be significantly elevated in sera of MS patients (n = 21), in both relapse and remission, compared to healthy controls (HC) (n = 24). This was not associated with the acute phase reaction (APR) as measured by serum C-reactive protein (CRP) level, which was similarly increased in MS patients compared to controls. An independent validation cohort from a different ethnic background showed a similar upward trend in mean sTLR2 values in relapsing-remitting MS (RRMS) patients, and significant differences in sTLR2 values between patients and HC were preserved when the data from the two cohorts were pooled together (n = 41 RRMS and 44 HC, P = 0.0006). TLR2-stimulants, measured using a human embryonic kidney (HEK)-293 cells transfectant reporter assay, were significantly higher in urine of MS patients than HC. A screen of several common urinary tract infections (UTI)-related organisms showed strong induction of TLR2-signaling in the same assay. Taken together, these results indicate that two different markers of TLR2-activity—urinary TLR2-stimulants and serum sTLR2 levels—are significantly elevated in MS patients compared to HC.
Collapse
Affiliation(s)
- Md Jakir Hossain
- Division of Clinical Neuroscience, University of Nottingham School of Medicine, Queen's Medical Centre, Nottingham, United Kingdom
| | - Elena Morandi
- Division of Clinical Neuroscience, University of Nottingham School of Medicine, Queen's Medical Centre, Nottingham, United Kingdom
| | - Radu Tanasescu
- Division of Clinical Neuroscience, University of Nottingham School of Medicine, Queen's Medical Centre, Nottingham, United Kingdom.,Department of Neurology, Neurosurgery and Psychiatry, University of Medicine and Pharmacy Carol Davila, Colentina Hospital, Bucharest, Romania
| | - Nanci Frakich
- Division of Clinical Neuroscience, University of Nottingham School of Medicine, Queen's Medical Centre, Nottingham, United Kingdom
| | - Marzia Caldano
- Neurologia - Centro Riferimento Regionale Sclerosi Multipla (CReSM), Neuroscience Institute Cavalieri Ottolenghi (NICO), San Luigi University Hospital, Orbassano, Turin, Italy
| | - David Onion
- School of Life Sciences, University of Nottingham Flow Cytometry Facility, University of Nottingham, Nottingham, United Kingdom
| | - Tola A Faraj
- Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, United Kingdom
| | - Clett Erridge
- Department of Cardiovascular Sciences, University of Leicester, Clinical Sciences Wing, Glenfield General Hospital, Leicester, United Kingdom.,Department of Biomedical and Forensic Sciences, Anglia Ruskin University, Cambridge, United Kingdom
| | - Bruno Gran
- Division of Clinical Neuroscience, University of Nottingham School of Medicine, Queen's Medical Centre, Nottingham, United Kingdom.,Department of Neurology, Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
| |
Collapse
|
|
33
|
Maev IV, Bakulin IG, Kurilovich SA, Bakulina NV, Andreev NG, Golubev NN. Helicobacter pylori and extragastroduodenal diseases: the proven facts and assumptions. DOKAZATEL'NAYA GASTROENTEROLOGIYA 2018; 7:45. [DOI: 10.17116/dokgastro2018703145] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
|
|
34
|
Wendel-Haga M, Celius EG. Is the hygiene hypothesis relevant for the risk of multiple sclerosis? Acta Neurol Scand 2017; 136 Suppl 201:26-30. [PMID: 29068485 DOI: 10.1111/ane.12844] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 08/31/2017] [Indexed: 12/30/2022]
Abstract
The hygiene hypothesis, suggesting that low exposure to pathogens early in life can increase the risk for immune-mediated diseases, has been proposed as an explanation for the increase in incidence of allergy and autoimmune diseases in industrialized countries during the last decades. Several aspects of the hygiene hypothesis have been related to MS. Already in 1966, the risk of MS was suggested to be higher in individuals with high hygienic standard during childhood. Further, an episode of infectious mononucleosis is an independent risk factor for MS and can be regarded as an indicator of low exposure to pathogens early in life, as infection with Epstein-Barr virus often is asymptomatic when it occurs in young children. Conflicting results have been reported regarding number of siblings, attendance in a day care center and exposure to animals during childhood in relation to MS risk, but common childhood infections and vaccinations do not seem to influence the risk of MS. In line with the hygiene hypothesis, two large meta-analyses have recently shown that infection with Helicobacter pylori is negatively correlated with MS. Moreover, a protective influence of helminth infection on MS has been observed in several, small clinical studies, but more knowledge is needed before a potential role of helminth-derived therapy in MS is determined. Also, it has been hypothesized that infection with the parasite Toxoplasma gondii could be protective against MS.
Collapse
Affiliation(s)
- M. Wendel-Haga
- Department of Neurology; Telemark Hospital; Skien Norway
- MS Research Group; Oslo University Hospital; Oslo Norway
| | - E. G. Celius
- MS Research Group; Oslo University Hospital; Oslo Norway
- Department of Neurology; Oslo University Hospital; Oslo Norway
- Institute of Health and Society; University of Oslo; Oslo Norway
| |
Collapse
|
|
35
|
de Korwin JD, Ianiro G, Gibiino G, Gasbarrini A. Helicobacter pylori infection and extragastric diseases in 2017. Helicobacter 2017; 22 Suppl 1. [PMID: 28891133 DOI: 10.1111/hel.12411] [Citation(s) in RCA: 32] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
The huge variety of extragastric diseases linked to Helicobacter pylori infection is widely known, and new studies are conducted every year on this topic. Neurological disorders and metabolic syndrome are some of the main issues debated in the most recent literature. Articles on the association of H. pylori with skin diseases, inflammatory bowel diseases, immunologic impairment, kidney dysfunction, allergic asthma, and respiratory diseases have been published as well. In this perspective, eradication therapy for this infection could become a mandatory measure in prevention strategy.
Collapse
Affiliation(s)
- Jean-Dominique de Korwin
- Department of Internal Medicine, University of Lorraine and University Hospital of Nancy, Nancy, France
| | - Gianluca Ianiro
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Catholic University of Rome, Milano, Italy
| | - Giulia Gibiino
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Catholic University of Rome, Milano, Italy
| | - Antonio Gasbarrini
- Department of Internal Medicine, Gastroenterology and Hepatology, Agostino Gemelli Hospital, Catholic University of Rome, Milano, Italy
| |
Collapse
|
|
36
|
Abstract
BACKGROUND The associations between allergies, antibiotics use, and multiple sclerosis (MS) remain controversial and their mediating or moderating effects have not yet been examined. We aimed to assess the direct and indirect influences of allergies and antibiotics use on MS development, and their interactions. METHODS A 1:3 matched case-control study was performed using the National Ambulatory Medical Care Survey database from 2006 to 2013 in the USA. Multiple sclerosis was identified based on the ICD-9 code (340.0) in any position. Cases were matched to their controls based on survey year, age, gender, race, payer type, region, and tobacco use. Allergy diseases and antibiotics prescriptions were extracted by ICD-9 code and drug classification code, respectively. Both generalized structural equation model and MacArthur approach were used to examine their intrinsic relationships. RESULTS The weighted prevalence of MS was 133.7 per 100,000 visits. A total of 829 MS patients and 2441 controls were matched. Both respiratory tract allergies (OR = 0.29, 95% CI: 0.18, 0.49) and other allergies (OR = 0.38, 95% CI: 0.19, 0.77) were associated with a reduction of the risk of MS. Patients with respiratory tract allergies were more likely to use penicillin (OR = 8.73, 95% CI: 4.12, 18.53) and other antibiotics (OR = 3.77, 95% CI: 2.72, 5.21), and those with other allergies had a higher likelihood of penicillin use (OR = 4.15, 95% CI: 1.27, 13.54); however, the link between antibiotics use and MS was not confirmed although penicillin use might mediate the relationship between allergies and MS. CONCLUSIONS The findings supported allergy as a protective factor for MS development. We also suggest antibiotics use might not be a suitable indicator of bacterial infection to investigate the cause of MS.
Collapse
Affiliation(s)
- Jinma Ren
- a Center for Outcomes Research , University of Illinois College of Medicine at Peoria , Peoria , Illinois , USA
| | - Huijuan Ni
- b Department of Mathematics , Illinois State University , Normal , Illinois , USA
| | - Minchul Kim
- a Center for Outcomes Research , University of Illinois College of Medicine at Peoria , Peoria , Illinois , USA
| | - Kimberly L Cooley
- c Research, Jump Simulation and Education Center , Peoria , Illinois , USA
- d Neurology, OSF Saint Francis Medical Center , Peoria , Illinois , USA
| | | | - Carl V Asche
- a Center for Outcomes Research , University of Illinois College of Medicine at Peoria , Peoria , Illinois , USA
- e Center for Pharmacoepidemiology & Pharmacoeconomic Research, University of Illinois College of Pharmacy at Chicago , Illinois , USA
| |
Collapse
|
|
37
|
Park AM, Omura S, Fujita M, Sato F, Tsunoda I. Helicobacter pylori and gut microbiota in multiple sclerosis versus Alzheimer's disease: 10 pitfalls of microbiome studies. CLINICAL & EXPERIMENTAL NEUROIMMUNOLOGY 2017; 8:215-232. [PMID: 29158778 DOI: 10.1111/cen3.12401] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Alteration of microbiota has been associated with intestinal, inflammatory, and neurological diseases. Abundance of "good bacteria" such as Bifidobacterium, or their products have been generally believed to be beneficial for any diseases, while "bad bacteria" such as pathogenic Helicobacter pylori are assumed to be always detrimental for hosts. However, this is not the case when we compare and contrast the association of the gut microbiota with two neurological diseases, multiple sclerosis (MS) and Alzheimer's disease (AD). Following H. pylori infection, pro-inflammatory T helper (Th)1 and Th17 immune response are initially induced to eradicate bacteria. However, H. pylori evades the host immune response by inducing Th2 cells and regulatory T cells (Tregs) that produce anti-inflammatory interleukin (IL)-10. Suppression of anti-bacterial Th1/Th17 cells by Tregs may enhance gastric H. pylori propagation, followed by a cascade reaction involving vitamin B12 and folic acid malabsorption, plasma homocysteine elevation, and reactive oxygen species induction. This can damage the blood-brain barrier (BBB), leading to accumulation of amyloid-β in the brain, a hallmark of AD. On the other hand, this suppression of pro-inflammatory Th1/Th17 responses to H. pylori has protective effects on the hosts, since it prevents uncontrolled gastritis as well as suppresses the induction of encephalitogenic Th1/Th17 cells, which can mediate neuroinflammation in MS. The above scenario may explain why chronic H. pylori infection is positively associated with AD, while it is negatively associated with MS. Lastly, we list "10 pitfalls of microbiota studies", which will be useful for evaluating and designing clinical and experimental microbiota studies.
Collapse
Affiliation(s)
- Ah-Mee Park
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Seiichi Omura
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Mitsugu Fujita
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Fumitaka Sato
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| | - Ikuo Tsunoda
- Department of Microbiology, Kindai University Faculty of Medicine, 377-2 Ohnohigashi, Osakasayama, Osaka 589-8511, Japan
| |
Collapse
|
|
38
|
Wood H. Could Helicobacter pylori provide protection against multiple sclerosis? Nat Rev Neurol 2016; 12:313. [DOI: 10.1038/nrneurol.2016.62] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
|
|
39
|
Banwell B, Giovannoni G, Hawkes C, Lublin F. Editors’ Welcome. Mult Scler Relat Disord 2016; 7:A1-2. [DOI: 10.1016/j.msard.2016.05.011] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/28/2022]
|