ArticleProceedings of the National Academy of Sciences of the United States of America2020
Indoles from the commensal microbiota act via the AHR and IL-10 to tune the cellular composition of the colonic epithelium during aging.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers, 1 of them a synthesis that pooled it.
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Who cites it
99 citing papers in PubMed, 1 synthesis or guideline pooled it, 140 citations in OpenAlex.
- Probiotics supplements for the prevention of atopic dermatitis in children: an umbrella review.Frontiers in nutrition · 2025Pooled it
- A Polyphenol-Rich Diet Increases the Gut Microbiota Metabolite Indole 3-Propionic Acid in Older Adults with Preserved Kidney Function.Molecular nutrition & food research · 2022Trial
- Gut microbiota shaping fatty liver disease progression.Life science alliance · 2027Review
- Review
- Microbiota-derived indole limitsScience advances · 2026Article
- AHR: The Overlooked Mediator in SkincareBridging Environmental Sensing and Skin Physiology.Environment & health (Washington, D.C.) · 2026Review
- Cell Signaling by Tryptophan Catabolism.Biochemistry · 2026Review
- Habitual coffee intake shapes the gut microbiome and modifies host physiology and cognition.Nature communications · 2026Article
- Gut microbiota-derived metabolites as immune modulators in aging and age-related chronic inflammatory diseases.Ageing research reviews · 2026Review
- Pseudomonas plecoglossicida disrupts intestinal homeostasis through manipulation of palmitoleic acid microbial metabolism.NPJ biofilms and microbiomes · 2026Article
- Probiotics in Irritable Bowel Syndrome: An Umbrella Review of 27 Systematic Reviews on Methodological Quality and Certainty of Evidence.Journal of clinical medicine · 2026Review
- Intestinal aging-related immune dysfunction: mechanisms and interventions.Acta biochimica et biophysica Sinica · 2026Review
- Gut microbiome-derived indoles differentially suppress type III secretion system-associated virulence inFrontiers in microbiology · 2026Article
- Gastrointestinal acute graft versus host disease: a translational perspective from pathogenesis to precision prevention and treatment.Frontiers in immunology · 2026Review
- Gut Metabolite Indoleacrylic Acid Suppresses Osteoclast Formation by AHR mediated NF-κB Signaling Pathway.International journal of biological sciences · 2026Article
- The microbiota-metabolite-immune axis in colorectal cancer: mechanistic insights and emerging clinical applications.Frontiers in immunology · 2026Review
- Longitudinal analysis of fecal tryptophan metabolites and microbiome composition in very preterm infants: impact of birth mode and feeding type.Gut microbes · 2025Article
- Microbiome dysbiosis and chemotherapy resistance in acute myeloid leukemia (AML).NPJ biofilms and microbiomes · 2025Review
- Tryptophan catabolites from microbiota ameliorate immune-mediated hepatitis through activating aryl hydrocarbon receptor of T cells.Gut microbes · 2025Article
- The microbial metabolite desaminotyrosine protects against graft-versus-host disease via mTORC1 and STING-dependent intestinal regeneration.Nature communications · 2025Article
39 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The intestinal epithelium is a highly dynamic structure that rejuvenates in response to acute stressors and can undergo alterations in cellular composition as animals age. The microbiota, acting via secreted factors related to indole, appear to regulate the sensitivity of the epithelium to stressors and promote epithelial repair via IL-22 and type I IFN signaling. As animals age, the cellular composition of the intestinal epithelium changes, resulting in a decreased proportion of goblet cells in the colon. We show that colonization of young or geriatric mice with bacteria that secrete indoles and various derivatives or administration of the indole derivative indole-3 aldehyde increases proliferation of epithelial cells and promotes goblet cell differentiation, reversing an effect of aging. To induce goblet cell differentiation, indole acts via the xenobiotic aryl hydrocarbon receptor to increase expression of the cytokine IL-10. However, the effects of indoles on goblet cells do not depend on type I IFN or on IL-22 signaling, pathways responsible for protection against acute stressors. Thus, indoles derived from the commensal microbiota regulate intestinal homeostasis, especially during aging, via mechanisms distinct from those used during responses to acute stressors. Indoles may have utility as an intervention to limit the decline of barrier integrity and the resulting systemic inflammation that occurs with aging.
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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.