Project description:Recently, gut metabolites have been recognized to play significant roles in liver diseases via the gut-liver axis. In this study, we investigate the regulatory effects of the tryptophan metabolite, indole-3-propionic acid (IPA), on immune cells during liver fibrogenesis using single-cell RNA sequencing (scRNA-seq).
Project description:Hepatocellular carcinoma is one of the most prevalent malignancies worldwide, and the role of stress in hepatocellular carcinoma progression remains incompletely understood. In this study, we integrated clinical and preclinical models to investigate how stress-associated gut microbiota remodeling contributes to hepatocellular carcinoma progression. Stress profoundly altered the gut microbiota, with Phocaeicola vulgatus significantly reduced. Restoration of Phocaeicola vulgatus or administration of its tryptophan-derived metabolite indole-3-propionic acid attenuated hepatocellular carcinoma progression in vivo. Single-cell RNA sequencing was performed to characterize changes in the hepatocellular carcinoma tumor microenvironment. Indole-3-propionic acid treatment reduced endothelial JAM2 expression and was associated with reduced JAM2-F11R-mediated endothelial-macrophage crosstalk. These findings support a role for the stress-gut microbiota-metabolite-tumor microenvironment axis in hepatocellular carcinoma progression and suggest potential translational targets for microbiome-based therapeutic strategies.
Project description:Purpose: compare the response of DRG neurons to indole-3-propionic acid treatment before and after sciatic nerve injury Results: we found that IPA induced transcription changes before and after injury inside the DRG tissue. In particular expression of immune system related genes
Project description:Maternal environmental exposures are critical in shaping offspring immunity. Yet, the role of helminths, mammals’ symbiotic evolutionary partners that have been eliminated from modern societies, remains poorly understood. Here, we show that maternal helminth infection enhances type I interferon (IFN-I) signaling in the offspring’s lung epithelium, conferring broad and lasting protection against respiratory viruses. Using cross-fostering, antibiotics, and gnotobiotic systems, we demonstrate that this antiviral immunity is mediated by helminth-altered maternal microbiota. Mechanistically, we identify the microbial tryptophan metabolite indole-3-propionic acid (IPA) as a key driver of IFN-I responses in lung epithelium. Furthermore, the tryptophan metabolic pathway is enriched in the microbiome of helminth-infected human populations, and IPA alone is sufficient to enhance IFN-I signaling in human bronchial epithelial cells. We uncover a conserved trans-kingdom mechanism by which maternal helminths imprint offspring antiviral immunity and propose that microbial metabolites could be harnessed to restore early-life antiviral defenses in helminth-depleted societies.
Project description:Acne vulgaris is a chronic inflammatory dermatosis where conventional therapies of-ten face limitations in efficacy and safety, necessitating the development of microbi-ome-targeted interventions. This study investigated the immunomodulatory potential of microbiome-derived tryptophan metabolites as a novel therapeutic strategy for Cutibacterium acnes-induced inflammation, focusing on the aryl hydrocarbon receptor (AHR) pathway. We evaluated indole-3-lactic acid (ILA), indole-3-acrylic acid (IAA), and indole-3-propionic acid (IPA) in comparison to tapinarof, utilizing C. ac-nes-stimulated human epidermal keratinocytes and a C. acnes-induced acne mouse model. In vitro, ILA and IPA significantly suppressed C. acnes-driven inflammatory mediators, including TNF-α, IL-1β, and COX2, whereas IAA demonstrated limited ef-ficacy. In vivo, ILA treatment exhibited superior therapeutic activity, markedly reduc-ing inflammatory cell infiltration, epidermal hyperplasia, and IL-1β expression. Tran-scriptomic analysis confirmed that ILA attenuates inflammatory signaling (e.g., IL-17 and TNF pathways) while upregulating AHR-responsive genes such as CYP1A1 and CYP1B1. Collectively, these findings establish ILA as a potent postbiotic that mitigates cutaneous inflammation through selective activation of the AHR. Future studies should prioritize the clinical translation of ILA-based topical fomulations, with rigorous evaluation of their efficacy and safety in well-designed human trials, to support their development as a non-antibiotic therapeutic alternative for acne management.
2026-01-05 | GSE315350 | GEO
Project description:Clostridium sporogenes and its tryptophan metabolite indole-3-propionic acid repair antibiotic-induced muscle atrophy in mice
Project description:Lactobacillus intestinalis-derived indole-3-propionic acid mediates benefits of maternal tryptophan metabolism on offspring intestinal health