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Gut microbiota is considered a contributing factor to multiple hepatic injuries. However, its role in NPs\u2010induced hepatic injuries remains unclear, and microbial intervention strategies are required. Our results reveal that oral exposure to polystyrene NPs reduces gut probiotic\n                    <jats:italic>Bifidobacterium pseudolongum<\/jats:italic>\n                    (\n                    <jats:italic>B.p<\/jats:italic>\n                    ) and its metabolite inosine. Gut microbiota from NPs\u2010administered mice partially reproduces NPs\u2010related impairment of gut homeostasis and hepatic injury in recipient mice. Moreover,\n                    <jats:italic>B.p<\/jats:italic>\n                    colonization improves NPs\u2010induced gut homeostasis impairment and hepatic injury, and its protective effects are reproduced by supplementation with inosine. Mechanically,\n                    <jats:italic>B.p<\/jats:italic>\n                    colonization increases hepatic level of inosine and subsequently normalizes the expression of its target A2AR. Meanwhile, increased inosine inhibits the miR155\/SOCS1\/NF\u2010\u03baB pathway and represses NPs\u2010induced M1 macrophage polarization. CGS21680, an agonist of A2AR, effectively represses lipopolysaccharide (LPS)\u2010induced M1 macrophage polarization and inhibits the miR155\/SOCS1\/NF\u2010\u03baB pathway in vitro. Further, miR155 knockout inhibits NPs\u2010induced M1 macrophage polarization, but does not influence the suppression of NPs on A2AR. These findings suggest that\n                    <jats:italic>B.p<\/jats:italic>\n                    \u2010derived inosine can repress NPs\u2010induced M1 macrophages polarization by inhibiting the miR155\/SOCS1\/NF\u2010\u03baB pathway via targeting A2AR. Altogether, this study further clarifies the role of gut microbiota in NPs\u2010induced hepatic injury and provides a potential microbial therapeutic strategy.\n                  <\/jats:p>","DOI":"10.1002\/advs.202522510","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T16:03:51Z","timestamp":1783353831000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Bifidobacterium Pseudolongum\u2010<\/i>\n                    Derived Inosine Mitigates Polystyrene Nanoplastics\u2010Induced Hepatic Injury by Inhibiting the Polarization of M1 Macrophages"],"prefix":"10.1002","volume":"13","author":[{"given":"Kaikai","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Multi\u2010Organ Injury Prevention and Treatment Key Laboratory of Infectious Diseases Research in South China Ministry of Education Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases Guangdong Provincial Clinical Research Center for Viral Hepatitis Guangdong Institute of Hepatology Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology..."},{"name":"Department of Gastroenterology Shunde Hospital of Southern Medical University Southern Medical University  Foshan China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Multi\u2010Organ Injury Prevention and Treatment Key Laboratory of Infectious Diseases Research in South China Ministry of Education Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases Guangdong Provincial Clinical Research Center for Viral Hepatitis Guangdong Institute of Hepatology Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayuan","family":"Wan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Multi\u2010Organ Injury Prevention and Treatment Key Laboratory of Infectious Diseases Research in South China Ministry of Education Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases Guangdong Provincial Clinical Research Center for Viral Hepatitis Guangdong Institute of Hepatology Guangdong Provincial Research Center for Liver Fibrosis Engineering and Technology..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianzheng","family":"Yang","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Forensic Multi\u2010Omics for Precision Identification School of Forensic Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijian","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Forensic Multi\u2010Omics for Precision Identification School of Forensic Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingyuan","family":"Li","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Forensic Multi\u2010Omics for Precision Identification School of Forensic Medicine Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anding","family":"Zhou","sequence":"additional","affiliation":[{"name":"Guangzhou Key Laboratory of Forensic Multi\u2010Omics for Precision Identification School of Forensic Medicine Southern Medical University  Guangzhou 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