{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE318nnn/GSE318635/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Mus musculus"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE318635"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Gut mycobiota-associated tryptophan catabolites protect against metabolic dysfunction-associated steatotic liver disease","description":"Accumulating evidence suggests that the intestinal microbiota participates in the development of metabolic dysfunction-associated steatotic liver disease (MASLD) through metabolite-host interaction. However, the beneficial role of commensal mycobiota in MASLD progression remains poorly understood. Comparing the gut microbiome differences, we demonstrated that the deficiency of Caspase Recruitment Domain-containing protein 9 (CARD9), an adaptor protein for a microbiota recognition receptor, exacerbated HFD-induced MASLD in a gut fungi-dependent manner. CARD9 deficiency reduced the abundance of Saccharomyces cerevisiae (S. cerevisiae), which was a probiotic alleviating MASLD progression. S.cerevisiae promoted a significantly greater abundance of 5-hydroxyindoleacetic acid (5-HIAA) in intestine through TLR1, which then alleviated MASLD phenotypes via “gut-liver” axis. Particularly, 5-HIAA directly bond to aryl-hydrocarbon receptor (AhR) and stimulated its nuclear translocation, subsequently inducing fatty acid oxidation via carnitine palmitoyl transferase 1A (CPT1A) and acyl-CoA oxidase 1 (ACOX1) transactivation. MASLD patients exhibited decreased levels of S. cerevisiae and 5-HIAA, and S.cerevisiae effectively ameliorated hepatic steatosis and improved glucose homeostasis in patients with MASLD. In summary, our findings identified a novel pathway of fungi-S. cerevisiae stimulating intestinal 5-HIAA production and indicated that S. cerevisiae and 5-HIAA might alleviate MASLD progression, highlighting that mycobiota-dependent gut-liver axis was a promising target for the prevention of MASLD.","dates":{"publication":"2026/07/15"},"accession":"GSE318635","cross_references":{"GSM":["GSM9499608","GSM9499609","GSM9499606","GSM9499607","GSM9499604","GSM9499605","GSM9499613","GSM9499614","GSM9499603","GSM9499611","GSM9499612","GSM9499610"],"GPL":["24247"],"GSE":["318635"],"taxon":["Mus musculus"],"PMID":["[42052722]"]}}