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Article: Modulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease

TitleModulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease
Authors
Keywordsalcoholic liver injury
berberine
granulocytic‐myeloid‐derived suppressor cell‐like population
gut microbiota
Issue Date2020
PublisherSpringerOpen. The Journal's web site is located at http://www.clintransmed.com
Citation
Clinical and Translational Medicine, 2020, v. 10 n. 4, p. article no. e112 How to Cite?
AbstractBackground: Berberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear. Aim: To investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota‐immune system axis. Method: An animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing. Results: We first reported the promising beneficial effect of berberine on ameliorating acute‐on‐chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota‐immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic‐ myeloid‐derived suppressor cell (G‐MDSC)‐like population, in the liver of mice with alleviating alcohol‐induced hepatic injury. Berberine remarkably enhanced the increase of G‐MDSC‐like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G‐MDSC‐like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G‐MSDCs‐like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G‐MDSC‐like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population. Conclusion: Collectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.
Persistent Identifierhttp://hdl.handle.net/10722/290934
ISSN
2019 Impact Factor: 7.919
2015 SCImago Journal Rankings: 0.124
PubMed Central ID
ISI Accession Number ID

 

DC FieldValueLanguage
dc.contributor.authorLi, S-
dc.contributor.authorWang, N-
dc.contributor.authorTan, HY-
dc.contributor.authorCheung, F-
dc.contributor.authorZhang, Z-
dc.contributor.authorYuen, MF-
dc.contributor.authorFeng, Y-
dc.date.accessioned2020-11-02T05:49:10Z-
dc.date.available2020-11-02T05:49:10Z-
dc.date.issued2020-
dc.identifier.citationClinical and Translational Medicine, 2020, v. 10 n. 4, p. article no. e112-
dc.identifier.issn2001-1326-
dc.identifier.urihttp://hdl.handle.net/10722/290934-
dc.description.abstractBackground: Berberine is an isoquinoline alkaloid compound derived from many herbs, which has been used extensively to improve liver function. But action mechanism of its hepatoprotection in alcoholic liver disease (ALD) is far from being clear. Aim: To investigate the underlying mechanism of berberine's therapeutic effect on ALD associated with gut microbiota‐immune system axis. Method: An animal model fed with ethanol that mimics drinking pattern ideally in ALD patients was established. Liver function was evaluated by biochemical test and histological examination. Immune cells were detected by flow cytometry and feces samples were collected for 16S rRNA gene amplicon sequencing. Results: We first reported the promising beneficial effect of berberine on ameliorating acute‐on‐chronic alcoholic hepatic damage and explored the underlying mechanism involving gut microbiota‐immune system axis. Notably, berberine activated a population with immune suppressive function, defined as granulocytic‐ myeloid‐derived suppressor cell (G‐MDSC)‐like population, in the liver of mice with alleviating alcohol‐induced hepatic injury. Berberine remarkably enhanced the increase of G‐MDSC‐like cells in blood and liver and decreased cytotoxic T cells correspondingly. Suppression of G‐MDSC‐like population significantly attenuated the protective effect of berberine against alcohol. Berberine activated IL6/STAT3 signaling in in vitro culture of G‐MSDCs‐like population, while inhibition of STAT3 activity attenuated the activation of this population by berberine. Moreover, berberine changed the overall gut microbial community, primarily increased the abundance of Akkermansia muciniphila. Of note, depletion of gut microbiota abolished the inducing effect of berberine on G‐MDSC‐like population, and attenuated its hepatoprotective effect against alcohol in mice, suggesting intestinal flora might be involved in mediating the expansion of this protective population. Conclusion: Collectively, this study delivered insight into the role of immunosuppressive response in ALD, and facilitated the understanding of the pharmacological effects and action mechanisms of berberine.-
dc.languageeng-
dc.publisherSpringerOpen. The Journal's web site is located at http://www.clintransmed.com-
dc.relation.ispartofClinical and Translational Medicine-
dc.rightsThis work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.-
dc.subjectalcoholic liver injury-
dc.subjectberberine-
dc.subjectgranulocytic‐myeloid‐derived suppressor cell‐like population-
dc.subjectgut microbiota-
dc.titleModulation of gut microbiota mediates berberine‐induced expansion of immuno‐suppressive cells to against alcoholic liver disease-
dc.typeArticle-
dc.identifier.emailLi, S: lishaha@hku.hk-
dc.identifier.emailWang, N: ckwang@hku.hk-
dc.identifier.emailTan, HY: hyhtan@hku.hk-
dc.identifier.emailZhang, Z: zhangzj@hkucc.hku.hk-
dc.identifier.emailYuen, MF: mfyuen@hku.hk-
dc.identifier.emailFeng, Y: yfeng@hku.hk-
dc.identifier.authorityWang, N=rp02075-
dc.identifier.authorityZhang, Z=rp01297-
dc.identifier.authorityYuen, MF=rp00479-
dc.identifier.authorityFeng, Y=rp00466-
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1002/ctm2.112-
dc.identifier.pmid32790968-
dc.identifier.pmcidPMC7438809-
dc.identifier.hkuros317968-
dc.identifier.volume10-
dc.identifier.issue4-
dc.identifier.spagearticle no. e112-
dc.identifier.epagearticle no. e112-
dc.identifier.isiWOS:000558905100001-
dc.publisher.placeSweden-

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