Unravelling the Link between the Gut Microbiome and Autoimmune Kidney Diseases: A Potential New Therapeutic Approach.

The gut microbiota and short chain fatty acids (SCFA) have been associated with immune regulation and autoimmune diseases. Autoimmune kidney diseases arise from a loss of tolerance to antigens, often with unclear triggers. In this review, we explore the role of the gut microbiome and how disease, diet, and therapy can alter the gut microbiota consortium. Perturbations in the gut microbiota may systemically induce the translocation of microbiota-derived inflammatory molecules such as liposaccharide (LPS) and other toxins by penetrating the gut epithelial barrier. Once in the blood stream, these pro-inflammatory mediators activate immune cells, which release pro-inflammatory molecules, many of which are antigens in autoimmune diseases. The ratio of gut bacteria Bacteroidetes/Firmicutes is associated with worse outcomes in multiple autoimmune kidney diseases including lupus nephritis, MPO-ANCA vasculitis, and Goodpasture's syndrome. Therapies that enhance SCFA-producing bacteria in the gut have powerful therapeutic potential. Dietary fiber is fermented by gut bacteria which in turn release SCFAs that protect the gut barrier, as well as modulating immune responses towards a tolerogenic anti-inflammatory state. Herein, we describe where the current field of research is and the strategies to harness the gut microbiome as potential therapy.

Emerging role of gut microbiota in autoimmune diseases.

Accumulating studies have indicated that the gut microbiota plays a pivotal role in the onset of autoimmune diseases by engaging in complex interactions with the host. This review aims to provide a comprehensive overview of the existing literatures concerning the relationship between the gut microbiota and autoimmune diseases, shedding light on the complex interplay between the gut microbiota, the host and the immune system. Furthermore, we aim to summarize the impacts and potential mechanisms that underlie the interactions between the gut microbiota and the host in autoimmune diseases, primarily focusing on systemic lupus erythematosus, rheumatoid arthritis, Sjögren's syndrome, type 1 diabetes mellitus, ulcerative colitis and psoriasis. The present review will emphasize the clinical significance and potential applications of interventions based on the gut microbiota as innovative adjunctive therapies for autoimmune diseases.

Prevalence and risk factors of non-tuberculous mycobacterial pulmonary isolates and infection in interstitial lung disease associated with systemic autoimmune disease.

OBJECTIVES: Non-tuberculous mycobacterial (NTM) lung disease (NTM-LD) prevalence is increasing worldwide. In this study, we aimed to evaluate the clinical significance of NTM pulmonary isolates (NTM-PI) and NTM-LD in patients with systemic autoimmune disease (SAD) who had a concurrent interstitial lung disease (ILD) diagnosis. METHODS: We retrospectively identified patients with SAD who had a concurrent ILD diagnosis (SAD-ILD) and from whom clinically indicated sputum specimens were collected for NTM culture between 2003 and 2018 at a tertiary referral hospital. We analysed the prevalence and risk factors of NTM pulmonary isolates (NTM-PI; ≥1 positive culture) and NTM-LD (≥2 positive cultures). RESULTS: This study included 258 patients. Rheumatoid arthritis and Sjögren's syndrome were the most common SADs (32.2% and 26.7%, respectively). The NTM-negative subgroup had 204 patients (79.1%) and the NTM-PI subgroup had 54 patients (20.9%). In the NTM-PI subgroup, 33 patients had one NTM positive set of specimens (NTM 1+, 12.8% of the entire sample) and 21 had NTM-LD (8.1% of the entire sample). In a multivariable analysis, chronic kidney disease (CKD; adjusted odds ratio [aOR]: 3.10 [1.53, 6.29]) and chronic obstructive pulmonary disease (COPD; aOR: 2.59 [1.16, 5.78]) were significantly associated with NTM-PI. For NTM-LD, CKD (aOR: 2.79 [1.00, 7.76]) and COPD (aOR: 3.70 [1.23, 10.72]) remained significant risk factors. CONCLUSIONS: In patients with SAD-ILD, the NTM-PI and NTM-LD prevalence rates were 20.9% and 8.1%, respectively. COPD and CKD were independent risk factors of both NTM-PI and NTM-LD. Previous use of biological agents was associated with NTM-PI.

How to Tackle the Relationship between Autoimmune Diseases and Diet: Well Begun Is Half-Done.

Nutrition and immunity are closely related, and the immune system is composed of the most highly energy-consuming cells in the body. Much of the immune system is located within the GI tract, since it must deal with the huge antigenic load introduced with food. Moreover, the incidence of immune-mediated diseases is elevated in Westernized countries, where "transition nutrition" prevails, owing to the shift from traditional dietary patterns towards Westernized patterns. This ecological correlation has fostered increasing attempts to find evidence to support nutritional interventions aimed at managing and reducing the risk of immune-mediated diseases. Recent studies have described the impacts of single nutrients on markers of immune function, but the knowledge currently available is not sufficient to demonstrate the impact of specific dietary patterns on immune-mediated clinical disease endpoints. If nutritional scientists are to conduct quality research, one of many challenges facing them, in studying the complex interactions between the immune system and diet, is to develop improved tools for investigating eating habits in the context of immunomediated diseases.

Crosstalk of Microorganisms and Immune Responses in Autoimmune Neuroinflammation: A Focus on Regulatory T Cells.

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.

Leveraging diet to engineer the gut microbiome.

Autoimmune diseases, including inflammatory bowel disease, multiple sclerosis and rheumatoid arthritis, have distinct clinical presentations but share underlying patterns of gut microbiome perturbation and intestinal barrier dysfunction. Their potentially common microbial drivers advocate for treatment strategies aimed at restoring appropriate microbiome function, but individual variation in host factors makes a uniform approach unlikely. In this Perspective, we consolidate knowledge on diet-microbiome interactions in local inflammation, gut microbiota imbalance and host immune dysregulation. By understanding and incorporating the effects of individual dietary components on microbial metabolic output and host physiology, we examine the potential for diet-based therapies for autoimmune disease prevention and treatment. We also discuss tools targeting the gut microbiome, such as faecal microbiota transplantation, probiotics and orthogonal niche engineering, which could be optimized using custom dietary interventions. These approaches highlight paths towards leveraging diet for precise engineering of the gut microbiome at a time of increasing autoimmune disease.

Lyme arthritis: linking infection, inflammation and autoimmunity.

Infectious agents can trigger autoimmune responses in a number of chronic inflammatory diseases. Lyme arthritis, which is caused by the tick-transmitted spirochaete Borrelia burgdorferi, is effectively treated in most patients with antibiotic therapy; however, in a subset of patients, arthritis can persist and worsen after the spirochaete has been killed (known as post-infectious Lyme arthritis). This Review details the current understanding of the pathogenetic events in Lyme arthritis, from initial infection in the skin, through infection of the joints, to post-infectious chronic inflammatory arthritis. The central feature of post-infectious Lyme arthritis is an excessive, dysregulated pro-inflammatory immune response during the infection phase that persists into the post-infectious period. This response is characterized by high amounts of IFNγ and inadequate amounts of the anti-inflammatory cytokine IL-10. The consequences of this dysregulated pro-inflammatory response in the synovium include impaired tissue repair, vascular damage, autoimmune and cytotoxic processes, and fibroblast proliferation and fibrosis. These synovial characteristics are similar to those in other chronic inflammatory arthritides, including rheumatoid arthritis. Thus, post-infectious Lyme arthritis provides a model for other chronic autoimmune or autoinflammatory arthritides in which complex immune responses can be triggered and shaped by an infectious agent in concert with host genetic factors.

Mining the capacity of human-associated microorganisms to trigger rheumatoid arthritis-A systematic immunoinformatics analysis of T cell epitopes.

Autoimmune diseases, often triggered by infection, affect ~5% of the worldwide population. Rheumatoid Arthritis (RA)-a painful condition characterized by the chronic inflammation of joints-comprises up to 20% of known autoimmune pathologies, with the tendency of increasing prevalence. Molecular mimicry is recognized as the leading mechanism underlying infection-mediated autoimmunity, which assumes sequence similarity between microbial and self-peptides driving the activation of autoreactive lymphocytes. T lymphocytes are leading immune cells in the RA-development. Therefore, deeper understanding of the capacity of microorganisms (both pathogens and commensals) to trigger autoreactive T cells is needed, calling for more systematic approaches. In the present study, we address this problem through a comprehensive immunoinformatics analysis of experimentally determined RA-related T cell epitopes against the proteomes of Bacteria, Fungi, and Viruses, to identify the scope of organisms providing homologous antigenic peptide determinants. By this, initial homology screening was complemented with de novo T cell epitope prediction and another round of homology search, to enable: i) the confirmation of homologous microbial peptides as T cell epitopes based on the predicted binding affinity to RA-related HLA polymorphisms; ii) sequence similarity inference for top de novo T cell epitope predictions to the RA-related autoantigens to reveal the robustness of RA-triggering capacity for identified (micro/myco)organisms. Our study reveals a much larger repertoire of candidate RA-triggering organisms, than previously recognized, providing insights into the underestimated role of Fungi in autoimmunity and the possibility of a more direct involvement of bacterial commensals in RA-pathology. Finally, our study pinpoints Endoplasmic reticulum chaperone BiP as the most potent (most likely mimicked) RA-related autoantigen, opening an avenue for identifying the most potent autoantigens in a variety of different autoimmune pathologies, with possible implications in the design of next-generation therapeutics aiming to induce self-tolerance by affecting highly reactive autoantigens.

A Role for Folate in Microbiome-Linked Control of Autoimmunity.

The microbiome exerts considerable control over immune homeostasis and influences susceptibility to autoimmune and autoinflammatory disease (AD/AID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS), type 1 diabetes (T1D), psoriasis, and uveitis. In part, this is due to direct effects of the microbiome on gastrointestinal (GI) physiology and nutrient transport, but also to indirect effects on immunoregulatory controls, including induction and stabilization of T regulatory cells (T reg). Secreted bacterial metabolites such as short-chain fatty acids (SCFA) are under intense investigation as mediators of these effects. In contrast, folate (vitamin B9), an essential micronutrient, has attracted less attention, possibly because it exerts global physiological effects which are difficult to differentiate from specific effects on the immune system. Here, we review the role of folate in AD/AID with some emphasis on sight-threatening autoimmune uveitis. Since folate is required for the generation and maintenance of T reg , we propose that one mechanism for microbiome-based control of AD/AID is via folate-dependent induction of GI tract T reg , particularly colonic T reg, via anergic T cells (T an). Hence, folate supplementation has potential prophylactic and/or therapeutic benefit in AID/AD.

The role of the microbiome in gastrointestinal inflammation.

The microbiome plays an important role in maintaining human health. Despite multiple factors being attributed to the shaping of the human microbiome, extrinsic factors such diet and use of medications including antibiotics appear to dominate. Mucosal surfaces, particularly in the gut, are highly adapted to be able to tolerate a large population of microorganisms whilst still being able to produce a rapid and effective immune response against infection. The intestinal microbiome is not functionally independent from the host mucosa and can, through presentation of microbe-associated molecular patterns (MAMPs) and generation of microbe-derived metabolites, fundamentally influence mucosal barrier integrity and modulate host immunity. In a healthy gut there is an abundance of beneficial bacteria that help to preserve intestinal homoeostasis, promote protective immune responses, and limit excessive inflammation. The importance of the microbiome is further highlighted during dysbiosis where a loss of this finely balanced microbial population can lead to mucosal barrier dysfunction, aberrant immune responses, and chronic inflammation that increases the risk of disease development. Improvements in our understanding of the microbiome are providing opportunities to harness members of a healthy microbiota to help reverse dysbiosis, reduce inflammation, and ultimately prevent disease progression.

Partners in Leaky Gut Syndrome: Intestinal Dysbiosis and Autoimmunity.

The intestinal surface is constitutively exposed to diverse antigens, such as food antigens, food-borne pathogens, and commensal microbes. Intestinal epithelial cells have developed unique barrier functions that prevent the translocation of potentially hostile antigens into the body. Disruption of the epithelial barrier increases intestinal permeability, resulting in leaky gut syndrome (LGS). Clinical reports have suggested that LGS contributes to autoimmune diseases such as type 1 diabetes, multiple sclerosis, rheumatoid arthritis, and celiac disease. Furthermore, the gut commensal microbiota plays a critical role in regulating host immunity; abnormalities of the microbial community, known as dysbiosis, are observed in patients with autoimmune diseases. However, the pathological links among intestinal dysbiosis, LGS, and autoimmune diseases have not been fully elucidated. This review discusses the current understanding of how commensal microbiota contributes to the pathogenesis of autoimmune diseases by modifying the epithelial barrier.

Prevotella diversity, niches and interactions with the human host.

The genus Prevotella includes more than 50 characterized species that occur in varied natural habitats, although most Prevotella spp. are associated with humans. In the human microbiome, Prevotella spp. are highly abundant in various body sites, where they are key players in the balance between health and disease. Host factors related to diet, lifestyle and geography are fundamental in affecting the diversity and prevalence of Prevotella species and strains in the human microbiome. These factors, along with the ecological relationship of Prevotella with other members of the microbiome, likely determine the extent of the contribution of Prevotella to human metabolism and health. Here we review the diversity, prevalence and potential connection of Prevotella spp. in the human host, highlighting how genomic methods and analysis have improved and should further help in framing their ecological role. We also provide suggestions for future research to improve understanding of the possible functions of Prevotella spp. and the effects of the Western lifestyle and diet on the host-Prevotella symbiotic relationship in the context of maintaining human health.

Klebsiella pneumoniae pneumonia in patients with rheumatic autoimmune diseases: clinical characteristics, antimicrobial resistance and factors associated with extended-spectrum ß-lactamase production.

BACKGROUND: Over the past decades, Klebsiella pneumoniae (K. pneumoniae) infections have been increasing and affected immunocompromised patients nosocomially and communally, with extended-spectrum ß-lactamase (ESBL) production becoming a major concern. Patients with rheumatic autoimmune diseases, mostly receiving immunosuppressive therapy, are vulnerable to various infections, including K. pneumoniae. However, few have investigated K. pneumoniae infections in this specific population. This study aimed to identify factors associated with ESBL production and mortality of K. pneumoniae pneumonia among patients with rheumatic autoimmune diseases in the Emergency Department. METHODS: We retrospectively investigated patients with rheumatic diseases who were diagnosed with K. pneumoniae pneumonia. The diagnosis of K. pneumoniae pneumonia was based on clinical manifestations, radiological findings and microbiological testing results. Prognostic factors and risk factors for ESBL production were determined with univariate and multivariate logistic regression analysis. Empirical therapy and antimicrobial susceptibility data were also collected. RESULTS: Of 477 K. pneumoniae pneumonia patients, 60 were enrolled into this study. The in-hospital mortality was 28.3%. Septic shock, ICU admission, the need for mechanical ventilation and change of antibiotics due to clinical deterioration, all related to mortality, were included as unfavorable clinical outcomes. Multivariate analysis suggested that ESBL production (OR, 6.793; p = 0.012), initial PCT ≥ 0.5 ng/ml (OR, 5.024; p = 0.033) and respiratory failure at admission (OR, 4.401; p = 0.046) predicted increased mortality. ESBL production was significantly associated with dose of corticosteroids (OR, 1.033; p = 0.008) and CMV viremia (OR, 4.836; p = 0.032) in patients with rheumatic autoimmune diseases. Abnormal leukocyte count (OR, 0.192; p = 0.036) was identified as a protective factor of ESBL-producing K. pneumoniae pneumonia. The most commonly used empirical antibiotic was ceftazidime, while most isolates showed less resistance to carbapenems and amikacin in susceptibility testing. CONCLUSIONS: K. pneumoniae pneumonia could be life-threatening in patients with rheumatic autoimmune diseases. Our findings suggested that ESBL production, initial PCT ≥ 0.5 ng/ml and respiratory failure at admission were independent factors associated with poor prognosis. Dose of corticosteroids and CMV viremia, predicting ESBL production in K. pneumoniae pneumonia, may help make individualized antibiotic decisions in clinical practice.

Intestinal Flora: A Pivotal Role in Investigation of Traditional Chinese Medicine.

Intestinal flora is essential for maintaining host health and plays a unique role in transforming Traditional Chinese Medicine (TCM). TCM, as a bodyguard, has saved countless lives and maintained human health in the long history, especially in this COVID-19 pandemic. Pains of diseases have been removed from the effective TCM therapy, such as TCM preparation, moxibustion, and acupuncture. With the development of life science and technology, the wisdom and foresight of TCM has been more displayed. Furthermore, TCM has been also inherited and developed in innovation to better realize the modernization and globalization. Nowadays, intestinal flora transforming TCM and TCM targeted intestinal flora treating diseases have been important findings in life science. More and more TCM researches showed the significance of intestinal flora. Intestinal flora is also a way to study TCM to elucidate the profound theory of TCM. Processing, compatibility, and properties of TCM are well demonstrated by intestinal flora. Thus, it is no doubt that intestinal flora is a core in TCM study. The interaction between intestinal flora and TCM is so crucial for host health. Therefore, it is necessary to sum up the latest results in time. This paper systematically depicted the profile of TCM and the importance of intestinal flora in host. What is more, we comprehensively summarized and discussed the latest progress of the interplay between TCM and intestinal flora to better reveal the core connotation of TCM.

Gut Commensal Segmented Filamentous Bacteria Fine-Tune T Follicular Regulatory Cells to Modify the Severity of Systemic Autoimmune Arthritis.

Autoantibodies play a major pathogenic role in rheumatoid arthritis. T follicular helper (Tfh) cells promote germinal center B cell and Ab responses. Excessive Tfh cell responses lead to autoimmunity, and therefore, counterregulation is crucial. T follicular regulatory (Tfr) cells, mainly differentiated from T regulatory cells, can negatively regulate Tfh and germinal center B cells. Dysbiosis is involved in rheumatoid arthritis's pathogenesis. We previously demonstrated that the gut microbiota, segmented filamentous bacteria (SFB), promote autoimmune arthritis by inducing Tfh cells. However, little is known regarding whether gut microbiota influence systemic (nongut) Tfr cells, impacting gut-distal autoimmunity. In this study, using SFB in autoimmune arthritic K/BxN mice, we demonstrated that SFB-induced arthritis is linked to the reduction of Tfr cells' CTLA-4, the key regulatory molecule of Tfr cells. This SFB-mediated CTLA-4 reduction is associated with increased Tfr glycolytic activity, and glycolytic inhibition increases Tfr cells' CTLA-4 levels and reduces arthritis. The surface expression of CTLA-4 is tied to TCR signaling strength, and we discovered that SFB-reduced CTLA-4 is associated with a reduction of Nur77, an indicator of TCR signaling strength. Nur77 is known for repressing glycolytic activity. Using a loss-of-function study, we demonstrated that Nur77+/- haplodeficiency increases glycolysis and reduces CTLA-4 on Tfr cells, which is associated with increased arthritis and anti-glucose-6-phosphate isomerase titers. Tfr-specific deletion (KRN.Foxp3CreBcl-6fl/fl) in autoimmune condition reveals that Tfr cells repress arthritis, Tfh cells, and autoantibody responses and that SFB can mitigate this repression. Overall, these findings demonstrated that gut microbiota distally impact systemic autoimmunity by fine-tuning Tfr cells.

Causal Relationship Between Gut Microbiota and Autoimmune Diseases: A Two-Sample Mendelian Randomization Study.

Background: Growing evidence has shown that alterations in gut microbiota composition are associated with multiple autoimmune diseases (ADs). However, it is unclear whether these associations reflect a causal relationship. Objective: To reveal the causal association between gut microbiota and AD, we conducted a two-sample Mendelian randomization (MR) analysis. Materials and Methods: We assessed genome-wide association study (GWAS) summary statistics for gut microbiota and six common ADs, namely, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, multiple sclerosis, type 1 diabetes (T1D), and celiac disease (CeD), from published GWASs. Two-sample MR analyses were first performed to identify causal bacterial taxa for ADs in discovery samples. Significant bacterial taxa were further replicated in independent replication outcome samples. A series of sensitivity analyses was performed to validate the robustness of the results. Finally, a reverse MR analysis was performed to evaluate the possibility of reverse causation. Results: Combining the results from the discovery and replication stages, we identified one causal bacterial genus, Bifidobacterium. A higher relative abundance of the Bifidobacterium genus was associated with a higher risk of T1D [odds ratio (OR): 1.605; 95% CI, 1.339-1.922; PFDR = 4.19 × 10-7] and CeD (OR: 1.401; 95% CI, 1.139-1.722; PFDR = 2.03 × 10-3), respectively. Further sensitivity analyses validated the robustness of the above associations. The results of reverse MR analysis showed no evidence of reverse causality from T1D and CeD to the Bifidobacterium genus. Conclusion: This study implied a causal relationship between the Bifidobacterium genus and T1D and CeD, thus providing novel insights into the gut microbiota-mediated development mechanism of ADs.

Discerning novel drug targets for treating Mycobacterium avium ss. paratuberculosis-associated autoimmune disorders: an in silico approach.

Mycobacterium avium subspecies paratuberculosis (MAP) exhibits 'molecular mimicry' with the human host resulting in several autoimmune diseases such as multiple sclerosis, type 1 diabetes mellitus (T1DM), Hashimoto's thyroiditis, Crohn's disease (CD), etc. The conventional therapy for autoimmune diseases includes immunosuppressants or immunomodulators that treat the symptoms rather than the etiology and/or causative mechanism(s). Eliminating MAP-the etiopathological agent might be a better strategy to treat MAP-associated autoimmune diseases. In this case study, we conducted a systematic in silico analysis to identify the metabolic chokepoints of MAP's mimicry proteins and their interacting partners. The probable inhibitors of chokepoint proteins were identified using DrugBank. DrugBank molecules were stringently screened and molecular interactions were analyzed by molecular docking and 'off-target' binding. Thus, we identified 18 metabolic chokepoints of MAP mimicry proteins and 13 DrugBank molecules that could inhibit three chokepoint proteins viz. katG, rpoB and narH. On the basis of molecular interaction between drug and target proteins finally eight DrugBank molecules, viz. DB00609, DB00951, DB00615, DB01220, DB08638, DB08226, DB08266 and DB07349 were selected and are proposed for treatment of three MAP-associated autoimmune diseases namely, T1DM, CD and multiple sclerosis. Because these molecules are either approved by the Food and Drug Administration or these are experimental drugs that can be easily incorporated in clinical studies or tested in vitro. The proposed strategy may be used to repurpose drugs to treat autoimmune diseases induced by other pathogens.

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.

Autoimmune diseases are considered as one of the most important disorders of the immune system, in which the prolonged and chronic processes eliminate self-tolerance to the auto-antigens. The prevalence of autoimmune diseases has been increasing worldwide in the recent years. According to the literature, biological processes such as the host genome, epigenetic events, environmental condition, drug consumption, and infectious agents are the most important risk factors that make the host susceptible to the development of autoimmune diseases. In the recent years, the role of Helicobacter pylori in the induction of autoimmune diseases has attracted extensive attention. Via molecular mimicry, epitope spreading, bystander activation, polyclonal activation, dysregulation in immune response, and highly immune-dominant virulence, such as cagA, H. pylori causes tissue damage, polarity, and proliferation of the host cells leading to the modulation of host immune responses. Moreover, given the large population worldwide infected with H. pylori, it seems likely that the bacterium may develop into autoimmune diseases through dysregulation of the immune response. The frequency and relationship between H. pylori infection and systemic lupus erythematosus, rheumatoid arthritis, autoimmune atrophy gastritis, and autoimmune pancreatitis were evaluated using the data from 43 studies involving 5052 patients. According to statistical analysis it is probable that infection with more virulent strains of H. pylori (such as H. pylori cagA positive) can increase the risk of autoimmune diseases. In addition, it was shown that infection with H. pylori can prevent the development of atrophic gastritis by stimulating inflammation in the gastric antrum. However, future studies should confirm the validity of this study.