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Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In-silico study.

ABSTRACT: Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immunogenic to host. This autoimmunity may make a protein molecule nonfunctional and thereby may be involved in late onset metabolic, autoimmune and inflammatory disorders such as, Diabetes, Rheumatoid Arthritis, Hyperlipidemias and Cancer. In this in-silico study we found a large number of peptides identical between human and gut bacteria which were binding to HLA-II alleles, and hence, likely to be auto-immunogenic. Further we observed that such autoimmune candidates were enriched in bacterial species belonging to Firmicutes and Proteobacteria phyla, which lead us to conclude that these phyla may have higher disease impact in genetically predisposed individuals. Functional annotation of human proteins homologous to candidate gut-bacterial peptides showed significant enrichment in metabolic processes and pathways. Cognitive trait, Ageing, Alzheimer, Type 2 diabetes, Chronic Kidney Failure (CKF), Chronic Obstructive Pulmonary Disease (COPD) and various Cancers were the major diseases represented in the dataset. This dataset provides us with gut bacterial autoimmune candidates which can be studied for their clinical significance in late onset diseases.

SUBMITTER: Negi S

PROVIDER: S-EPMC5498033 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In-silico study.

Negi Sapna S Singh Harpreet H Mukhopadhyay Anirban A

PloS one 20170705 7

Recent evidences suggest that human gut microbiota with major component as bacteria can induce immunity. It is also known that gut lining depletes with ageing and that there is increased risk of autoimmune and inflammatory disorders with ageing. It is therefore likely that both may be correlated as depletion of gut lining exposes the gut bacterial antigens to host immune mechanisms, which may induce immunity to certain bacterial proteins, but at the same time such immunity may also be auto-immun ...[more]

PMID: 28678867

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Project description:AIMS/HYPOTHESIS:We sought to assess the frequency, determinants and prognosis for future diabetes in individuals with islet autoimmunity and whether these factors differ depending on the age of onset of islet autoimmunity. METHODS:A prospective cohort (n = 2547) of children from the general population who had a high-risk HLA genotype and children who had a first-degree relative with type 1 diabetes were followed for up to 21 years. Those with the persistent presence of one or more islet autoantibodies were categorised as early-onset (<8 years of age, n = 143, median 3.3 years) or late-onset (?8 years of age, n = 64, median 11.1 years), and were followed for a median of 7.4 and 4.7 years, respectively. Progression to diabetes was evaluated by Kaplan-Meier analysis with logrank test. Factors associated with progression to diabetes were analysed using the parametric accelerated failure time model. RESULTS:Children with late-onset islet autoimmunity were more likely to be Hispanic or African-American than non-Hispanic white (p = 0.004), and less likely to be siblings of individuals with type 1 diabetes (p = 0.04). The frequencies of the HLA-DR3/4 genotype and non-HLA gene variants associated with type 1 diabetes did not differ between the two groups. However, age and HLA-DR3/4 were important predictors of rate of progression to both the presence of additional autoantibodies and type 1 diabetes. Late-onset islet autoimmunity was more likely to present with a single islet autoantibody (p = 0.01) and revert to an antibody-negative state (p = 0.01). Progression to diabetes was significantly slower in children with late-onset islet autoimmunity (p < 0.001). CONCLUSIONS/INTERPRETATION:A late onset of islet autoimmunity is more common in African-American and Hispanic individuals. About half of those with late-onset islet autoimmunity progress to show multiple islet autoantibodies and develop diabetes in adolescence or early adulthood. Further investigation of environmental determinants of late-onset autoimmunity may lead to an understanding of and ability to prevent adolescent and adult-onset type 1 diabetes.

Dataset Information

Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In-silico study.

Publications

Gut bacterial peptides with autoimmunity potential as environmental trigger for late onset complex diseases: In-silico study.

Similar Datasets

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