Oncogenic induction of cellular high CpG methylation by Epstein-Barr Barr virus in malignant epithelial cells

Epstein-Barr virus(EBV)is a well-known human herpesvirus associated with virtually all nasopharyngeal carcinoma(NPC)and^10%of gastric cancer(GC)worldwide.Increasing evidence shows that acquired genetic and epigenetic alterations lead to the initiation and progression of NPC and GC.However,even deep whole exome sequencing studies showed a relatively low frequency of gene mutations in NPC and EBV-associated GC(EBVa GC),suggesting a predominant role of epigenetic abnormities,especially promoter Cp G methylation,in the pathogenesis of NPC and EBVa GC.High frequencies of promoter methylation of tumor suppressor genes(TSGs)have been frequently reported in NPC and EBVa GC,with several EBV-induced methylated TSGs identified.Further characterization of the epigenomes(genome-wide Cp G methylation profile—methylome)of NPC and EBVa GC shows that these EBV-associated tumors display a unique high Cp G methylation epigenotype with more extensive gene methylation accumulation,indicating that EBV acts as a direct epigenetic driver for these cancers.Mechanistically,oncogenic modulation of cellular Cp G methylation machinery,such as DNA methyltransferases(DNMTs),by EBV-encoded viral proteins accounts for the EBV-induced high Cp G methylation epigenotype in NPC and EBVa GC.Thus,uncovering the EBV-associated unique epigenotype of NPC and EBVa GC would provide new insight into the molecular pathogenesis of these unique EBVassociated tumors and further help to develop pharmacologic strategies targeting cellular methylation machinery in these malignancies.

Baseline gut microbiota and metabolome predict durable immunogenicity to SARS-CoV-2 vaccines

The role of gut microbiota in modulating the durability of cOVID-19 vaccine immunity is yet to be characterised.In this cohort study,we collected blood and stool samples of 121 BNT162b2 and 40 CoronaVac vaccinees at baseline,1 month,and 6 months post vaccination(p.v).Neutralisation antibody,plasma cytokine and chemokines were measured and associated with the gut microbiota and metabolome composition.

Multi-omic analyses identify mucosa bacteria and fecal metabolites associated with weight loss after fecal microbiota transplantation

Fecal microbiota transplantation(FMT)has shown promising results in animal models of obesity,while results in human studies are inconsistent.We aimed to determine factors associated with weight loss after FMT in nine obese subjects using serial multi-omics analysis of the fecal and mucosal microbiome.The mucosal microbiome,fecal microbiome,and fecal metabolome showed individual clustering in each subject after FMT.The colonic microbiome in patients showed more marked variance after FMT compared with the duodenal microbiome,characterized by an increased relative abundance of Bacteroides.Subjects who lost weight after FMT sustained enrichment of Bifidobacterium bifidum and Alistipes onderdonkii in the duodenal,colonic mucosal,and fecal microbiome and increased levels of phosphopantothenate biosynthesis and fecal metabolite eicosapentaenoic acid(EPA),compared with those without weight loss.Fecal levels of amino acid metabolism-associated were positively correlated with the fecal abundance of B.bifidum,and fatty acid metabolism-associated metabolites showed positive correlations with A.onderdonkii.