The potential role of molecular mimicry by the anaerobic microbiota in the aetiology of autoimmune disease

English, Jamie; Patrick, Sheila; Stewart, Linda

doi:10.1016/j.anaerobe.2023.102721

Cited by 4 publications

(4 citation statements)

References 137 publications

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“…35,36 Similarly, cross-reactive molecularly mimicry may be at play in the immune tissue of the gastrointestinal mucosa or against gastrointestinal commensals in IBD. 37,38 Alternatively, under the immune exhaustion hypothesis, EBV infection in the acute phase could be exhausting the immune system’s resources, potentially increasing vulnerability to IBD in genetically susceptible individuals as is also seen in MS with EBV-specific T-lymphocytes eventually becoming exhausted through cytokine polyfunctionality. 39…”

Section: Discussionmentioning

confidence: 99%

Risk of Inflammatory Bowel Disease Following Hospitalisation with Infectious Mononucleosis: A Danish Nationwide Cohort Study (1977-2021)

Ebert,

Harper,

Vestergaard

et al. 2024

Preprint

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Background:Infectious mononucleosis (IM) is a largely self-limiting syndrome mainly affecting adolescents and young adults but can present as a more severe disease requiring hospitalisation. The infectious agent most commonly causing IM, Epstein-Barr virus (EBV) has been associated with the development of several immune-mediated and inflammatory diseases.Objective:To investigate the risk of inflammatory bowel disease (IBD) following hospitalisation with severe IM.Methods:Danish nationwide registries were used to identify severe IM patients and sex-, age- and municipality- matched non-IM hospitalised controls, from 1st January 1977 to 31st December 2022. We undertook Cox regression modelling to calculate the hazards (HR) and 95% CI of IBD diagnosis, including Crohn's disease (CD) and ulcerative colitis (UC). Analyses were stratified by sex and age at IM hospitalisation.Results:We identified 39,684 patients with severe IM who were sex-, age-, and municipality-matched to 396,840 non-IM hospitalised controls. Severe IM was significantly associated with the development of IBD (HR:1.35; 95% CI: 1.22-1.49) and this was seen particularly in CD (HR: 1.56; 95% CI: 1.34-1.83) and to a lesser extent in UC (HR: 1.23; 95% CI: 1.08-1.40). Sex at severe IM diagnosis was not found to be a significant modifier to the risk of IBD development with risk increased in both females (HR: 1.36; 95% CI: 1.20-1.55) and males (HR: 1.34; 95% CI: 1.17-1.54). Only those receiving a severe IM diagnosis at 10-16 years (HR: 1.42; 95% CI:1.22-1.64) or 17-29 years (HR: 1.34; 95% CI:1.15-1.56) were at increased risk of IBD development.Conclusion:This study demonstrated an association between IM hospitalisation and later IBD development, indicating an association between severe EBV disease and IBD development. Further exploration of factors contributing to IBD susceptibility following EBV infection is warranted.

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Section: Discussionmentioning

confidence: 99%

Risk of Inflammatory Bowel Disease Following Hospitalisation with Infectious Mononucleosis: A Danish Nationwide Cohort Study (1977-2021)

Ebert,

Harper,

Vestergaard

et al. 2024

Preprint

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“…Following are some examples of the potential involvement of GEMs in chronic human diseases driven by disequilibrated gut homeostasis ( Table 2 ): Autoimmune diseases: Various ADs are associated with specific [ 83 , 84 , 85 , 86 ] or pathobiont [ 87 ]. Type 1 diabetes, multiple sclerosis, celiac disease and psoriasis are some of them [ 88 ].…”

Section: Gems’ Horizontal Gene Exchanges Might Induce Human Diseasesmentioning

confidence: 99%

“… Metabolic diseases: All the components of the metabolic syndrome are related to a perturbated gut microbiome, hazardous mobilome, and disbalance of a fine synergistic luminal homeostasis [ 93 , 94 , 95 , 96 ]. Harmful proteinomes and metabolomes, increased intestinal permeability, post-translational modification of naïve peptides to immunogenic ones, cross-reactive autoantibodies, sequence similarity, molecular mimicry, bacterial fragments blood translocation and some other auto-immunogenic pathways might drive GEM involvement in metabolic conditions [ 2 , 85 , 96 , 97 ]. Allergic conditions: Food allergy is highly related to intestinal dysbiosis, and eubiotic equilibrium might protect allergy patients [ 98 ].…”

Section: Gems’ Horizontal Gene Exchanges Might Induce Human Diseasesmentioning

confidence: 99%

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The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

Lerner,

Benzvi,

Vojdani

2024

Microorganisms

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Gut luminal dysbiosis and pathobiosis result in compositional and biodiversified alterations in the microbial and host co-metabolites. The primary mechanism of bacterial evolution is horizontal gene transfer (HGT), and the acquisition of new traits can be achieved through the exchange of mobile genetic elements (MGEs). Introducing genetically engineered microbes (GEMs) might break the harmonized balance in the intestinal compartment. The present objectives are: 1. To reveal the role played by the GEMs’ horizontal gene transfers in changing the landscape of the enteric microbiome eubiosis 2. To expand on the potential detrimental effects of those changes on the human genome and health. A search of articles published in PubMed/MEDLINE, EMBASE, and Scielo from 2000 to August 2023 using appropriate MeSH entry terms was performed. The GEMs’ horizontal gene exchanges might induce multiple human diseases. The new GEMs can change the long-term natural evolution of the enteric pro- or eukaryotic cell inhabitants. The worldwide regulatory authority’s safety control of GEMs is not enough to protect public health. Viability, biocontainment, and many other aspects are only partially controlled and harmful consequences for public health should be avoided. It is important to remember that prevention is the most cost-effective strategy and primum non nocere should be the focus.

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Increased Intestinal Permeability: An Avenue for the Development of Autoimmune Disease?

2023

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The intestinal epithelium acts as the first line of defence against pathogens present in the lumen of the gastrointestinal tract. The epithelium is composed of a single monolayer that includes a variety of cell types, each of which play roles in nutrient and water absorption, antimicrobial defence, and immunomodulation to maintain a homeostatic gut environment. Tight junction (TJ) complexes between adjacent intestinal epithelial cells are responsible for the structural integrity of the gut barrier and controlling the paracellular translocation of luminal contents. The effectiveness of TJs can be impacted by both genetic and environmental factors including microbiota dysbiosis and dietary components. The increased systemic entry of luminal contents has been associated with the development, progression, and/or relapse of autoimmune diseases such as Crohn’s and rheumatoid arthritis. In particular, the extraintestinal spread of luminal microbes possessing components with structural similarity to those of the human host are thought to be involved in the breakdown of immune tolerance towards host components. Here, the structure and function of the intestinal epithelium are discussed as well as the genetic and environmental factors that influence its permeability. There is emphasis on the role of increased intestinal permeability and how the subsequent translocation of luminal contents could be involved in the development and/or exacerbation of autoimmune diseases. This review reinforces how protecting the integrity of the intestinal epithelium and minimising immunological exposure to luminal components, either directly or indirectly, could be a useful strategy in reducing the prevalence and severity of autoimmune diseases.

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The potential role of molecular mimicry by the anaerobic microbiota in the aetiology of autoimmune disease

Cited by 4 publications

References 137 publications

Risk of Inflammatory Bowel Disease Following Hospitalisation with Infectious Mononucleosis: A Danish Nationwide Cohort Study (1977-2021)

Risk of Inflammatory Bowel Disease Following Hospitalisation with Infectious Mononucleosis: A Danish Nationwide Cohort Study (1977-2021)

The Potential Harmful Effects of Genetically Engineered Microorganisms (GEMs) on the Intestinal Microbiome and Public Health

Increased Intestinal Permeability: An Avenue for the Development of Autoimmune Disease?

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