ArticleThe Journal of experimental medicine2022
Lysophosphatidylserines derived from microbiota in Crohn's disease elicit pathological Th1 response.
Article in The Journal of experimental medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 39 citations in OpenAlex.
- Excessive HIF-1α driven by phospholipid metabolism causes septic cardiomyopathy through cytopathic hypoxia.Nature cardiovascular research · 2025Article
- Microbiota metabolite taurodeoxycholic acid maintains intestinal tissue residency of innate lymphoid cells via engagement with P2Y10 receptor.Science advances · 2025Article
- Limosilactobacillus reuteri prevents progression of ankylosing spondylitis in mice by restoring gut microbiota-metabolism homeostasis.Journal of translational medicine · 2025Article
- Host-pathobiont interactions in Crohn's disease.Nature reviews. Gastroenterology & hepatology · 2025Review
- Integrative analysis of metabolomics and transcriptomics reveals alterations in egg quality and hepatic lipid metabolism in hens supplemented with curcumin.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2025Article
- Association of distinct microbial and metabolic signatures with microscopic colitis.Nature communications · 2025Article
- Age-related alterations in gut homeostasis are microbiota dependent.NPJ biofilms and microbiomes · 2025Article
- Review
- Ganglion cell-derived LysoPS induces retinal neovascularisation by activating the microglial GPR34-PI3K-AKT-NINJ1 axis.Journal of neuroinflammation · 2024Article
- The involvement of oral bacteria in inflammatory bowel disease.Gastroenterology report · 2024Review
- Prokaryotic and viral genomes recovered from 787 Japanese gut metagenomes revealed microbial features linked to diets, populations, and diseases.Cell genomics · 2022Article
- Fueling the fire in the gut.The Journal of experimental medicine · 2022Article
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19 authors at 2 institutions in 1 country.
Funding
Abstract
Microbiota alteration and IFN-γ-producing CD4+ T cell overactivation are implicated in Crohn's disease (CD) pathogenesis. However, it remains unclear how dysbiosis enhances Th1 responses, leading to intestinal inflammation. Here, we identified key metabolites derived from dysbiotic microbiota that induce enhanced Th1 responses and exaggerate colitis in mouse models. Patients with CD showed elevated lysophosphatidylserine (LysoPS) concentration in their feces, accompanied by a higher relative abundance of microbiota possessing a gene encoding the phospholipid-hydrolyzing enzyme phospholipase A. LysoPS induced metabolic reprogramming, thereby eliciting aberrant effector responses in both human and mouse IFN-γ-producing CD4+ T cells. Administration of LysoPS into two mouse colitis models promoted large intestinal inflammation. LysoPS-induced aggravation of colitis was impaired in mice lacking P2ry10 and P2ry10b, and their CD4+ T cells were hyporesponsive to LysoPS. Thus, our findings elaborate on the mechanism by which metabolites elevated in patients with CD harboring dysbiotic microbiota promote Th1-mediated intestinal pathology.
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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 Socratic graph.