Petitfils, C. | bioRxiv Science

bioRxiv2025

Fecal Dysosmobacter spp. concentration is linked to plasma lipidome in insulin-resistant individuals with overweight, obesity and metabolic syndrome

BackgroundObesity is reaching epidemic proportions worldwide. This excessive increase of adipose tissue is a risk factor for the development of multiple diseases and premature death. Amongst associated diseases, metabolic syndrome is one of the main comorbidities of obesity. In this context, the gut microbiota has been recognized as both shaping and responding to host energy metabolism. Recently metabolomics has emerged as a powerful tool to capture a snapshot of the metabolites present in a specific tissue, offering new insights into host-microbiota interactions. Integrating metabolomics with gut microbiota studies could help us better understand how specific species impact on host metabolomic profile. Dysosmobacter welbionis has been identified as a promising next generation beneficial bacteria with potential effects on fat mass and glucose metabolism in mice, and fecal Dysosmobacter spp concentration was inversely correlated to body mass index fasting glucose and plasmatic HbA1c in humans. MethodsConcentration of Dysosmobacter spp was quantified by qPCR in the stools of insulin resistant overweight/obese participants with a metabolic syndrome and plasma metabolites were analyzed using untargeted metabolomics. Correlations between Dysosmobacter spp fecal abundance and the 1169 identified plasma metabolites were uncovered using Spearman correlations followed by a false discovery rate correction. ResultsInterestingly, among the detected metabolites, Dysosmobacter spp was exclusively associated with lipid molecules, primarily structural lipids involved in membrane formation. This finding aligns with previous in vivo studies highlighting lipid profile alterations in multiple tissues of mice treated with this bacterium. ConclusionThese results suggest that Dysosmobacter spp plays a specific role in host lipid metabolism. Further studies are needed to elucidate the underlying mechanisms and assess its potential therapeutic applications.

physiology↗

bioRxiv2021

T helper cell-licensed mast cells promote inflammatory Th17 cells

CD4+ T helper cells (Th) infiltrate sites of inflammation and orchestrate the immune response by instructing local leukocytes. Mast cells (MCs) are tissue sentinel cells particularly abundant in skin and mucosa. Here, we analyzed the interplay between human MCs and Th cells and, through the application of RNAseq and functional assays, showed that Th cells induced a specific transcriptomic program in helped MCs (named here MCTH) driving them toward an inflammatory phenotype. The gene signature of MCTH indicated that MCs helped by Th cell acquired in turn the capacity to regulate effector T cell response through wide-range of soluble and membrane ligands. Accordingly, we showed that MCTH promoted Th17 cells and notably an inflammatory subset of Th17, producing both IFN-{gamma} and GM-CSF, through a PGE2 and IL-1{beta} axis. Our findings demonstrate that activated effector/memory CD4+ T cells activate and instruct resting MCs toward a specific differentiated pro-inflammatory phenotype endowed with the capacity to speak back to effector T cells and to mold their functions.

immunology↗