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Article: Probiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice

TitleProbiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice
Authors
Issue Date2016
PublisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org
Citation
Proceedings of the National Academy of Sciences, 2016, v. 113 n. 9, p. E1306-E1315 How to Cite?
AbstractThe beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.
Persistent Identifierhttp://hdl.handle.net/10722/227647
ISSN
2015 Impact Factor: 9.423
2015 SCImago Journal Rankings: 6.883
PubMed Central ID

 

DC FieldValueLanguage
dc.contributor.authorLi, J-
dc.contributor.authorSung, CYJ-
dc.contributor.authorLee, NPY-
dc.contributor.authorNi, YQ-
dc.contributor.authorPihlajamäki, J-
dc.contributor.authorPanagiotou, I-
dc.contributor.authorEl-Nezami, H-
dc.date.accessioned2016-07-18T09:11:59Z-
dc.date.available2016-07-18T09:11:59Z-
dc.date.issued2016-
dc.identifier.citationProceedings of the National Academy of Sciences, 2016, v. 113 n. 9, p. E1306-E1315-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10722/227647-
dc.description.abstractThe beneficial roles of probiotics in lowering the gastrointestinal inflammation and preventing colorectal cancer have been frequently demonstrated, but their immunomodulatory effects and mechanism in suppressing the growth of extraintestinal tumors remain unexplored. Here, we adopted a mouse model and metagenome sequencing to investigate the efficacy of probiotic feeding in controlling s.c. hepatocellular carcinoma (HCC) and the underlying mechanism suppressing the tumor progression. Our result demonstrated that Prohep, a novel probiotic mixture, slows down the tumor growth significantly and reduces the tumor size and weight by 40% compared with the control. From a mechanistic point of view the down-regulated IL-17 cytokine and its major producer Th17 cells, whose levels decreased drastically, played critical roles in tumor reduction upon probiotics feeding. Cell staining illustrated that the reduced Th17 cells in the tumor of the probiotic-treated group is mainly caused by the reduced frequency of migratory Th17 cells from the intestine and peripheral blood. In addition, shotgun-metagenome sequencing revealed the crosstalk between gut microbial metabolites and the HCC development. Probiotics shifted the gut microbial community toward certain beneficial bacteria, including Prevotella and Oscillibacter, that are known producers of antiinflammatory metabolites, which subsequently reduced the Th17 polarization and promoted the differentiation of antiinflammatory Treg/Tr1 cells in the gut. Overall, our study offers novel insights into the mechanism by which probiotic treatment modulates the microbiota and influences the regulation of the T-cell differentiation in the gut, which in turn alters the level of the proinflammatory cytokines in the extraintestinal tumor microenvironment.-
dc.languageeng-
dc.publisherNational Academy of Sciences. The Journal's web site is located at http://www.pnas.org-
dc.relation.ispartofProceedings of the National Academy of Sciences-
dc.rightsProceedings of the National Academy of Sciences. Copyright © National Academy of Sciences.-
dc.titleProbiotics modulated gut microbiota suppresses hepatocellular carcinoma growth in mice-
dc.typeArticle-
dc.identifier.emailLee, NPY: nikkilee@hku.hk-
dc.identifier.emailPanagiotou, I: gipa@hku.hk-
dc.identifier.authorityLee, NPY=rp00263-
dc.identifier.authorityPanagiotou, I=rp01725-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1073/pnas.1518189113-
dc.identifier.pmid26884164-
dc.identifier.pmcidPMC4780612-
dc.identifier.scopuseid_2-s2.0-84959314003-
dc.identifier.hkuros258939-
dc.identifier.volume113-
dc.identifier.issue9-
dc.identifier.spageE1306-
dc.identifier.epageE1315-
dc.publisher.placeUnited States-

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