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Effect of microbiota metabolites on the progression of chronic hepatitis B virus infection

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Abstract

Accumulating evidence shows that the intestinal microbiota is closely related to the pathophysiology and the disease progression of chronic hepatitis B virus (HBV) infection. The intestinal microbiota acts on the host through its metabolites. This review aimed to discuss the effects of gut microbiota metabolites on the disease progression of chronic HBV infection. A literature search on PubMed database and Wiley Online Library with pre-specified criteria yielded 96 unique results. After consensus by all authors, the contents from 86 original publications were extracted and included in this review. In liver disease with HBV infection, the intestinal microbiota changed in different stages and affected the production of bacterial metabolites. The abundance of bacteria producing short-chain fatty acids such as butyrate reduced, which was associated with bacterial translocation and the progression of liver disease. The intestinal microbiota—bile acid—host axis was destroyed, affecting the progression of the disease. Under the control of intestinal microbiota, tryptophan affected the gut–liver axis through three main metabolic pathways, among which the kynurenine pathway was closely related to the immune response of hepatitis B. The level of trimethylamine-N-oxide decreased in liver cancer with HBV infection and were used as a potential biomarker of liver cancer. Vitamin deficiencies, including those of vitamin D and vitamin A related to microbiota, were common and associated with survival. Hydrogen sulfide regulated by the intestinal microbiota was also closely related to the gut–liver axis. In liver disease with hepatitis B infection, the intestinal microbiota is imbalanced, and a variety of intestinal microbiota metabolites participate in the occurrence and development of the disease.

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Abbreviations

Ac-p53:

Acetylated p53

AMPs:

Antimicrobial peptides

AhR:

Aryl hydrocarbon Receptor

AhR-IL22:

AhR-dependent interleukin 22

BAs:

Bile acids

BSH:

Bile salt hydrolase

CHB:

Chronic hepatitis B

Conv-R mice:

Conventionally raised mice

CYP7A1:

Cholesterol 7α-hydroxylase

CXCL:

Chemokine C-X-C motif ligand

CSE:

Cystathionine γ-lyase

DOX:

Doxycycline

DAC:

Deoxycholic acid

FXR:

Farnesol-X receptor

FGF15:

Fibroblast growth factor 15

FGF19:

Fibroblast growth factor 19

GLP-1:

Glucagon-like peptide-1

GF mice:

Germ-free mice

HDAC:

Histone deacetylase

5-HT:

5-Hydroxytryptamine

H2S:

Hydrogen sulfide

IDO-1:

Indoleamine 2,3-dioxygenase-1

Kyn:

Kynurenine

KP:

Kynurenine pathway

Kyn/Try:

Kynurenine/tryptophan

LCMV:

Lymphocytic choriomeningitis virus

mTOR:

Mammalian target of rapamycin

NTCP:

Sodium taurocholate cotransport peptides

PCLS:

Precision-cut liver slices

peg-IFN:

Pegylated interferon-α 2a

SCFAs:

Short-chain fatty acids

SPF mice:

Specific pathogen-free mice

SIRT-1:

Sirtuin-1

SHP:

Small heterodimer partner

SSRIs:

Selective serotonin reuptake inhibitors

TGR5:

Takeda G-protein coupled receptor 5

Trp:

Tryptophan

TUDCA:

Tauroursodeoxycholic acid

TDO:

Tryptophan 2,3-dioxygenase

TNF-a:

Tumor necrosis factor a

TPH1:

Tryptophan hydroxylase 1

TMA:

Trimethylamine

TMAO:

Trimethylamine-N-oxide

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Funding

This work was supported by the National Science and Technology Major Project of China under Grant (2018ZX10302-206-003-006); the Capital's Funds for Health Improvement and Research under Grant (CFH 2020-1-2171 and CFH 2018-2-2173); the Beijing Hospitals Authority Clinical Medicine Development of Special Funding under Grant (XMLX201837); the Digestive Medical Coordinated Development Center of Beijing Hospitals Authority under Grant (XXT26).

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Authors and Affiliations

  1. Center of Liver Diseases Division 3, Beijing Ditan Hospital, Capital Medical University, 8 Jingshundong Street, Chaoyang District, Beijing, 100015, China

    Xiu Sun & Huichun Xing

  2. Peking University Ditan Teaching Hospital, Beijing, 100015, China

    Huichun Xing

  3. Division of Gastroenterology and Hepatology, NYU Langone Health, New York University School of Medicine, New York, USA132-21 41Ave, Flushing, NY, 11355, USA

    Calvin Q. Pan

  4. Center of Liver Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China

    Calvin Q. Pan

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  1. Xiu Sun
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HX, CQP and XS had designed the article, XS performed the literature search and data analysis, and XS drafted the manuscript and HX, CQP critically revised the manuscript for important intellectual content and finally approved the version to be submitted.

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Sun, X., Pan, C.Q. & Xing, H. Effect of microbiota metabolites on the progression of chronic hepatitis B virus infection. Hepatol Int 15, 1053–1067 (2021). https://doi.org/10.1007/s12072-021-10230-6

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