Dataset Information

Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire.

ABSTRACT: Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, 16S rRNA gene sequencing (16S-seq) and bulk immune repertoire sequencing (IR-seq) were performed to characterize GM and intrahepatic TCR IR. Fecal microbial transplant (FMT) and TCR? knockout (Tcrb^KO) mouse models were employed to determine the biological link between GM and TCR IR in liver fibrosis. We found that GM and intrahepatic TCR IR are highly correlated, with both showing reduced diversity and centralized distribution during liver fibrosis. The restoration of normal intestinal microbiota may reshape intrahepatic TCR IR and delay liver fibrosis. Interestingly, TCR IR ablation abrogated the impact of GM on liver fibrogenesis. Furthermore, GM modulated hepatic stellate cell (HSC) activation via TCR IR-mediated intrahepatic immune milieu. Our study demonstrates that GM, which exhibits cross-talk with the intrahepatic TCR IR, influences the intrahepatic immune microenvironment and liver fibrosis progression.

SUBMITTER: Liang Q

PROVIDER: S-EPMC7729130 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire.

Liang Qing Q Zhang Meina M Hu Yudi Y Zhang Wei W Zhu Ping P Chen Yujie Y Xue Pengxin P Li Qiyuan Q Wang Kejia K

Frontiers in microbiology 20201127

Gut microbiota (GM) modifies the intrahepatic immune microenvironment, but the underlying mechanisms remain poorly understood. Liver fibrosis-associated imprinting is predicted to be reflected in GM. This study investigated the link between GM and the intrahepatic T cell receptor (TCR) immune repertoire (IR), and whether GM modulates the intrahepatic immune microenvironment via TCR IR during liver fibrosis. We analyzed the correlation between GM and TCR IR during liver fibrogenesis. Accordingly, ...[more]

PMID: 33329430

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Project description:Background - Prepregnancy overweight and obesity promote deleterious health impacts on both mothers during pregnancy and the offspring. Significant changes in the maternal peripheral blood mononuclear cells (PBMCs) gene expression due to obesity are well-known. However, during pregnancy the impact of overweight on immune cell gene expression and its association with maternal and infant outcomes is not well explored. Methods – Blood samples were collected from healthy normal weight (NW, BMI 18.5-24.9) or overweight (OW, BMI 25-29.9) 2nd parity pregnant women at 12, 24 and 36 weeks of pregnancy. PBMCs were isolated from the blood and subjected to mRNA sequencing. Maternal and infant microbiota were analyzed by 16S rRNA gene sequencing. Integrative multi-omics data analysis was performed to evaluate the association of gene expression with maternal diet, gut microbiota, milk composition, and infant gut microbiota. Results - Gene expression analysis revealed that 453 genes were differentially expressed in the OW women compared to NW women at 12 weeks of pregnancy, out of which 354 were upregulated and 99 were downregulated. Several up-regulated genes in the OW group were enriched in inflammatory, chemokine-mediated signaling and regulation of interleukin-8 production-related pathways. At 36 weeks of pregnancy healthy eating index score was positively associated with several genes that include, DTD1, ELOC, GALNT8, ITGA6-AS1, KRT17P2, NPW, POT1-AS1 and RPL26. In addition, at 36 weeks of pregnancy, genes involved in adipocyte functions, such as NG2 and SMTNL1, were negatively correlated to human milk 2’FL and total fucosylated oligosaccharides content collected at 1 month postnatally. Furthermore, infant Akkermansia was positively associated with maternal PBMC anti-inflammatory genes that include CPS1 and RAB7B, at 12 and 36 weeks of pregnancy. Conclusions – These findings suggest that prepregnancy overweight impacts the immune cell gene expression profile, particularly at 12 weeks of pregnancy. Further, deciphering the complex association of PBMC’s gene expression levels with maternal gut microbiome and milk composition and infant gut microbiome may aid in developing strategies to mitigate obesity-mediated effects.

Dataset Information

Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire.

Publications

Gut Microbiome Contributes to Liver Fibrosis Impact on T Cell Receptor Immune Repertoire.

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