Blood: Intestinal microbiome triamine N-oxide aggravates GVHD by inducing M1 macrophage polarization

The diversity of the human microbial community indicates the difference in the effects of intestinal microbial metabolites on allogeneic transplants for host disease (GVHD), although short-chain fatty acids and radon have been shown to reduce their severityThis study analyzed the role of choline metabolites triamine N-oxide (TMAO) in gvHD in miceThe TMAO or high choline diet enhances the allogeneic GVH response, while choline analogue 3,3-dimethyl-1-butol reverses The severity of TMAO-induced GVHDInterestingly, TMAO-induced allogeneic T-cell proliferation and T-assisted cell (Th) subtype differentiation were observed in GVHD mice, but were not observed in in vitro culturethe researchers further studied the role of macropolarization of macrophages, which are not available in the in vitro culture systemIn TMAO-induced GVHD tissue and TMAO-cultured marrow-derived macrophages (BMDMs), the levels of F4/80-CD11b/CD16/32-M1 macrophages and signature genes IL-1 beta, IL-6, TNF-alpha, CXCL9 and CXCL10 increasedInhibiting the M1 characteristics of NLRP3 inflammatory small body reversing TMAO stimulation suggests that NLRP3 is the key protein hydrolysis activation factor for macrophage response to triamcinolone stimulationconsistentwith, mitochondrial reactive oxygen and enhanced NF-B nuclear relocation were observed in TMAO-stimulated BMDMsKnocking out the NLRP3 of the GVHD receptor not only closed M1 activation, but also reversed the severity of GVHD in the case of TMAO treatment, this study reveals that TMAO-induced GVHD progression is caused by the differentiation of Th1 and Th17, which is mediated by polarized M1 macrophages that rely on NLRP3 inflammatory small cellsThis study provides a link between host choline diet, microbial metabolites and GVH response, and provides a basis for reducing GVHD by controlling choline diet