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Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response.

ABSTRACT: Gut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were collected for 16s rRNA sequencing. Fecal metabolomics was measured with untargeted liquid chromatography-mass spectrometry in subgroups of 58 subjects. Lineage changes of peripheral blood mononuclear cells (PBMCs) were determined upon exposure to bacterial extracts (BE) from HBV-CLD patients. Integrated analyses of microbiome with metabolome revealed a remarkable shift of gut microbiota and metabolites in HBV-CLD patients, and disease progression and antiviral treatment were found to be two main contributing factors for the shift. Concordant decreases in Turicibacter with 4-hydroxyretinoic acid were detected to be inversely correlated with serum AST levels through host-microbiota-metabolite interaction analysis in cirrhotic patients. Moreover, depletion of E.hallii group with elevated choline was restored in patients with 5-year antiviral treatment. PBMC exposure to BE from non-cirrhotic patients enhanced expansion of T helper 17 cells; however, BE from cirrhotics attenuated T helper 1 cell count. CHB progression and antiviral treatment are two main factors contributing to the compositional shift in microbiome and metabolome of HBV-CLD patients. Peripheral immunity might be an intermediate link in gut microbe-host interplay underlying CHB pathogenesis.

SUBMITTER: Shen Y

PROVIDER: S-EPMC9757487 | biostudies-literature | 2023 Jan-Dec

REPOSITORIES: biostudies-literature

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Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response.

Shen Yue Y Wu Sheng-Di SD Chen Yao Y Li Xin-Yue XY Zhu Qin Q Nakayama Kiyoko K Zhang Wan-Qin WQ Weng Cheng-Zhao CZ Zhang Jun J Wang Hai-Kun HK Wu Jian J Jiang Wei W

Gut microbes 20230101 1

Gut dysbiosis has been reported in chronic hepatitis B (CHB) infection, however its role in CHB progression and antiviral treatment remains to be clarified. Herein, the present study aimed to characterize gut microbiota (GM) in patients with chronic hepatitis B virus infection-associated liver diseases (HBV-CLD) by combining microbiome with metabolome analyses and to evaluate their effects on peripheral immunity. Fecal samples from HBV-CLD patients (n = 64) and healthy controls (n = 17) were col ...[more]

PMID: 36519342

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Project description:Individuals with latent tuberculosis infection (LTBI) account for almost 30% of the population worldwide and have the potential to develop active tuberculosis (ATB). Despite this, the current understanding of the pathogenesis of LTBI is limited. The gut microbiome can be altered in tuberculosis patients, and an understanding of the changes associated with the progression from good health to LTBI to ATB can provide novel perspectives for understanding the pathogenesis of LTBI by identifying microbial and molecular biomarkers associated therewith. In this study, fecal samples from healthy controls (HC), individuals with LTBI and ATB patients were collected for gut microbiome and metabolomics analyses. Compared to HC and LTBI subjects, participants with ATB showed a significant decrease in gut bacterial α-diversity. Additionally, there were significant differences in gut microbial communities and metabolism among the HC, LTBI, and ATB groups. PICRUSt2 analysis revealed that microbiota metabolic pathways involving the degradation of purine and pyrimidine metabolites were upregulated in LTBI and ATB individuals relative to HCs. Metabolomic profiling similarly revealed that purine and pyrimidine metabolite levels were decreased in LTBI and ATB samples relative to those from HCs. Further correlation analyses revealed that the levels of purine and pyrimidine metabolites were negatively correlated with those of gut microbial genera represented by Ruminococcus_gnavus_group (R. gnavus), and the levels of R. gnavus were also positively correlated with adenosine nucleotide degradation II, which is a purine degradation pathway. Moreover, a combined signature including hypoxanthine and xanthine was found to effectively distinguish between LTBI and HC samples (area under the curve [AUC] of training set = 0.796; AUC of testing set = 0.924). Therefore, through gut microbiome and metabolomic analyses, these findings provide valuable clues regarding how alterations in gut purine and pyrimidine metabolism are linked to the pathogenesis of LTBI.IMPORTANCEThis study provides valuable insight into alterations in the gut microbiome and metabolomic profiles in a cohort of adults with LTBI and ATB. Perturbed gut purine and pyrimidine metabolism in LTBI was associated with the compositional alterations of gut microbiota, which may be an impetus for developing novel diagnostic strategies and interventions targeting LTBI.

Project description:BackgroundHIV-1 infection is characterized by a massive depletion of mucosal CD4 T cells that triggers a cascade of events ultimately linking gut microbial dysbiosis to HIV-1 disease progression and pathogenesis. The association between HIV infection and the enteric virome composition is less characterized, although viruses are an essential component of the gut ecosystem. Here, we performed a cross-sectional analysis of the fecal viral (eukaryotic viruses and bacteriophages) and bacterial microbiome in people with HIV (PWH) and in HIV-negative individuals. To gain further insight into the association between the gut microbiome composition, HIV-associated immunodeficiency, and immune recovery, we carried out a longitudinal study including 14 PWH who initiated antiretroviral therapy (ART) and were followed for 24 months with samplings performed at baseline (before ART) and at 2, 6, 12, and 24 months post-ART initiation.ResultsOur data revealed a striking expansion in the abundance and prevalence of several human virus genomic sequences (Anelloviridae, Adenoviridae, and Papillomaviridae) in stool samples of PWH with severe immunodeficiency (CD4 < 200). We also noted a decreased abundance of sequences belonging to two plant viruses from the Tobamovirus genus, a reduction in bacterial alpha diversity, and a decrease in Inoviridae bacteriophage sequences. Short-term ART (24 months) was linked to a significant decrease in human Anelloviridae sequences. Remarkably, the detection of Anellovirus sequences at baseline independently predicted poor immune recovery, as did low CD4 T cell counts. The bacterial and bacteriophage populations were unique to each PWH with individualized trajectories; we found no discernable pattern of clustering after 24 months on ART.ConclusionAdvanced HIV-1 infection was associated with marked alterations in the virome composition, in particular a remarkable expansion of human anelloviruses, with a gradual restoration after ART initiation. In addition to CD4 T cell counts, anellovirus sequence detection might be useful to predict and monitor immune recovery. This study confirms data on the bacteriome and expands our knowledge on the viral component of the gut microbiome in HIV-1 infection. Video Abstract.

Dataset Information

Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response.

Publications

Alterations in gut microbiome and metabolomics in chronic hepatitis B infection-associated liver disease and their impact on peripheral immune response.

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