ArticleProceedings of the National Academy of Sciences of the United States of America2015
Microbiota regulates type 1 diabetes through Toll-like receptors.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 1 of them a synthesis that pooled it.
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Who cites it
101 citing papers in PubMed, 1 synthesis or guideline pooled it, 171 citations in OpenAlex.
- Fecal microbiota transplantation treatment of autoimmune-mediated type 1 diabetes: A systematic review.Frontiers in cellular and infection microbiology · 2022Pooled it
- The Role of Microbiota in Type 1 Diabetes: Insights into Dysbiosis and Immune Interactions.Nutrients · 2026Review
- [Gut microbiota dysbiosis in type 1 diabetes mellitus: Impacts, mechanisms, and interventions].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2026Review
- Endotoxin Tolerance Impinges on T Cell Activation and Chemoattraction in Autoimmune Diabetes.Journal of immunology research · 2026Article
- Human Gut Commensal Bacteroides fragilis Suppresses Mucin Production and Alters Microbiota Composition Resulting in Accelerated Type 1 Diabetes in Mice.Immunology · 2026Article
- Modulating the Gut Microbiome in Type 2 Diabetes: Nutritional and Therapeutic Strategies.Nutrients · 2025Review
- Article
- Gut microbiota development across the lifespan: Disease links and health-promoting interventions.Journal of internal medicine · 2025Review
- Influence of gut microbiota on the pediatric endocrine system and associated disorders.Annals of medicine and surgery (2012) · 2025Review
- Targeting the TLR4 axis with microbiota-oriented interventions and innovations in diabetes therapy: a narrative review.Frontiers in immunology · 2025Review
- Sensing danger in the islet: the roles of pattern recognition receptors in β cells and type 1 diabetes.Frontiers in immunology · 2025Review
- Advancing Animal Models of Human Type 1 Diabetes.Cold Spring Harbor perspectives in medicine · 2024Review
- Gut microbiome shifts in people with type 1 diabetes are associated with glycaemic control: an INNODIA study.Diabetologia · 2024Article
- Dietary emulsifier consumption accelerates type 1 diabetes development in NOD mice.NPJ biofilms and microbiomes · 2024Article
- Engineering Probiotics for Diabetes Management: Advances, Challenges, and Future Directions in Translational Microbiology.International journal of nanomedicine · 2024Review
- TLR5-deficiency controls dendritic cell subset development in an autoimmune diabetes-susceptible model.Frontiers in immunology · 2024Article
- Mutual modulation of gut microbiota and the immune system in type 1 diabetes models.Nature communications · 2023Article
- A Supportive Role of Mesenchymal Stem Cells on Insulin-Producing Langerhans Islets with a Specific Emphasis on The Secretome.Biomedicines · 2023Review
- Pathobionts from chemically disrupted gut microbiota induce insulin-dependent diabetes in mice.Microbiome · 2023Article
- Microbiota-dependent proteolysis of gluten subverts diet-mediated protection against type 1 diabetes.Cell host & microbe · 2023Article
41 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Deletion of the innate immune adaptor myeloid differentiation primary response gene 88 (MyD88) in the nonobese diabetic (NOD) mouse model of type 1 diabetes (T1D) results in microbiota-dependent protection from the disease: MyD88-negative mice in germ-free (GF), but not in specific pathogen-free conditions develop the disease. These results could be explained by expansion of particular protective bacteria ("specific lineage hypothesis") or by dominance of negative (tolerizing) signaling over proinflammatory signaling ("balanced signal hypothesis") in mutant mice. Here we found that colonization of GF mice with a variety of intestinal bacteria was capable of reducing T1D in MyD88-negative (but not wild-type NOD mice), favoring the balanced signal hypothesis. However, the receptors and signaling pathways involved in prevention or facilitation of the disease remained unknown. The protective signals triggered by the microbiota were revealed by testing NOD mice lacking MyD88 in combination with knockouts of several critical components of innate immune sensing for development of T1D. Only MyD88- and TIR-domain containing adapter inducing IFN β (TRIF) double deficient NOD mice developed the disease. Thus, TRIF signaling (likely downstream of Toll-like receptor 4, TLR4) serves as one of the microbiota-induced tolerizing pathways. At the same time another TLR (TLR2) provided prodiabetic signaling by controlling the microbiota, as reduction in T1D incidence caused by TLR2 deletion was reversed in GF TLR2-negative mice. Our results support the balanced signal hypothesis, in which microbes provide signals that both promote and inhibit autoimmunity by signaling through different receptors, including receptors of the TLR family.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.