Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota

Chou, Han-Hsuan; Chien, Wei-Hung; Wu, Li-Ling; Cheng, Chi-Hung; Chung, Chen-Han; Horng, Jau-Haw; Ni, Yen-Hsuan; Tseng, Hong-Tai; Wu, Dafei; Lu, Xuemei; Wang, Hurng-Yi; Chen, Pei-Jer; Chen, Ding-Shinn

doi:10.1073/pnas.1424775112

Cited by 218Hepatitis B Virus StudiesGut microbiota and healthLiver physiology and pathology

Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota

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Chou, Han-Hsuan, Chien, Wei-Hung, Wu, Li-Ling, Cheng, Chi-Hung, Chung, Chen-Han, Horng, Jau-Haw, Ni, Yen-Hsuan, Tseng, Hong-Tai +5 more·2015·Proceedings of the National Academy of Sciences

DOI 10.1073/pnas.1424775112PMC PMC4343154

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Abstract

Significance: Ninety-five percent of adult-acquired infections lead to spontaneous clearance, whereas >90% of exposed neonates and ∼30% of children aged 1–5 y fail to resolve hepatitis B virus (HBV) and develop chronic infection. A strong, diverse, adaptive immune response is considered essential for HBV clearance, but the mechanisms to generate a favorable response remain elusive. Here, we show that, while 12-wk-old C3H/HeN mice cleared HBV within 6 wk postinjection (wpi), their 6-wk-old counterparts remained HBV-positive at 26 wpi. Sterilization of gut microbiota from 6 to 12 wk of age using antibiotics prevented mice from rapidly clearing HBV. This model is valuable to the study of liver tolerance and enables the investigation of the mechanisms involved in effective control of HBV.

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The gut microbiota controls immune responses and tolerance to HBV in adult mice, and six weeks of antibiotic treatment prevented HBV clearance.
“A recent study demonstrated that the gut microbiota controls immune responses and tolerance to HBV in adult mice, with 6 weeks of antibiotic treatment preventing the clearance of HBV68.”
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Authors: Chou, H.-H., Chien, W.-H., Wu, L.-L., Cheng, C.-H., Chung, C.-H., Horng, J.-H., Ni, Y.-H., Tseng, H.-T., Wu, D., Lu, X., Wang, H.-Y., Chen, P.-J., & Chen, D.-S.
Affiliations: National Taiwan University (TW)
Chinese Academy of Sciences (CN)
ORCID: Wu, Li-Ling
Ni, Yen-Hsuan
Lu, Xuemei
Wang, Hurng-Yi
Chen, Pei-Jer
Chen, Ding-Shinn
Venue: Proceedings of the National Academy of Sciences
Publisher: National Academy of Sciences
Published: 2015-02-02
Volume: 112
Issue: 7
Pages: 2175-2180
ISSN: 0027-8424 (ISSN-L)
1091-6490
DOI: 10.1073/pnas.1424775112
PMC: PMC4343154
OpenAlex: W2143865587
Cited by: 211
References: 34
Citations by year: 2026: 5 · 2025: 18 · 2024: 19 · 2023: 18 · 2022: 18 · 2021: 24 · 2020: 31 · 2019: 22 · 2018: 14 · 2017: 21 · 2016: 10 · 2015: 11
FWCI: 14.65
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Proceedings of the National Academy of Sciences (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Topics: Health Sciences › Medicine › Epidemiology › Hepatitis B Virus Studies
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
Health Sciences › Medicine › Hepatology › Liver physiology and pathology
Keywords: hepatitis B virus, viral clearance, age-related immunity, gut microbiota, TLR4, antibiotic-induced microbiota depletion, liver immunity, immune tolerance, C3H/HeN mice, C3H/HeJ mice
MeSH terms: Animals, Hepatitis B, Humans, Intestines, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, Microbiota

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Age-related immune clearance of hepatitis B virus infection requires the establishment of gut microbiota

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