{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T09:39:03Z","timestamp":1791279543073,"version":"4.1.0"},"reference-count":31,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2022,1,1]],"date-time":"2022-01-01T00:00:00Z","timestamp":1640995200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81904121"],"award-info":[{"award-number":["81904121"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009329","name":"Guangxi Science and Technology Planning Project","doi-asserted-by":"publisher","award":["BK20191087"],"award-info":[{"award-number":["BK20191087"]}],"id":[{"id":"10.13039\/501100009329","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,11,17]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Acute kidney injury (AKI) is a global public health hazard with high morbidity and mortality. Sepsis accounts for nearly half of all causes of AKI. Scientists have made a great effort to explore effective therapeutic agents with limited side effects in the treatment of AKI, but have had little success. With the development of gut flora study, Akkermansia muciniphila (A. muciniphila) has been proven to prevent different organs by regulating the inflammatory response. However, the reno-protective function is still unknown. Here, the AKI model was induced using lipopolysaccharide (LPS) in mice with or without pretreatment of A. muciniphila. Renal function and histological change were measured. Inflammatory factors were detected by ELISA and rt-PCR. TLR4\/NF-\u03baB signaling factors and NLRP3 inflammasome were tested by western blot and immunohistochemistry. Pretreatment of A. muciniphila markedly inhibited inflammatory response and ameliorated kidney histopathological changes. Furthermore, the TLR4, p-NF-\u03baB p65, and downstream I\u03baB\u03b1 were notably activated in the model group and inhibited by A. muciniphila. A similar effect was found in the regulation of NLRP3 inflammasome. In conclusion, pretreatment with A. muciniphila could protect against LPS-induced AKI by inhibition of the TLR4\/NF-\u03baB pathway and NLRP3 inflammasome activation. It may be a new therapeutic strategy for AKI prevention and treatment in the future.<\/jats:p>","DOI":"10.1093\/femsle\/fnac103","type":"journal-article","created":{"date-parts":[[2022,10,27]],"date-time":"2022-10-27T17:34:53Z","timestamp":1666892093000},"source":"Crossref","is-referenced-by-count":23,"title":["<i>Akkermansia muciniphila<\/i>\n                    attenuates LPS-induced acute kidney injury by inhibiting TLR4\/NF-\u03baB pathway"],"prefix":"10.1093","volume":"369","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6879-2716","authenticated-orcid":false,"given":"Jun","family":"Shi","sequence":"first","affiliation":[{"name":"School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing 210023, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Feng","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Analytical & Testing Center, Nanjing Medical University , Nanjing 211166, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Tang","sequence":"additional","affiliation":[{"name":"Renal Division, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiqiang","family":"Li","sequence":"additional","affiliation":[{"name":"Renal Division, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manshu","family":"Yu","sequence":"additional","affiliation":[{"name":"Renal Division, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Bai","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing 210023, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zebin","family":"Weng","sequence":"additional","affiliation":[{"name":"School of Traditional Chinese Medicine & School of Integrated Chinese and Western Medicine, Nanjing University of Chinese Medicine , Nanjing 210023, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meixiao","family":"Sheng","sequence":"additional","affiliation":[{"name":"Renal Division, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"He","sequence":"additional","affiliation":[{"name":"Renal Division, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugen","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Colorectal Surgery, Affiliated Hospital of Nanjing University of Chinese Medicine , Nanjing 210029, PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2022,11,11]]},"reference":[{"key":"2022111716591004100_bib1","doi-asserted-by":"crossref","first-page":"2564","DOI":"10.1681\/ASN.2016020177","article-title":"Of inflammasomes and alarmins: iL-1beta and IL-1alpha in kidney disease","volume":"27","author":"Anders","year":"2016","journal-title":"J Am Soc Nephrol"},{"key":"2022111716591004100_bib2","doi-asserted-by":"crossref","first-page":"256","DOI":"10.4103\/ijn.IJN_366_18","article-title":"Dietary management in slowing down the progression of CKDu","volume":"30","author":"Anupama","year":"2020","journal-title":"Indian J Nephrol"},{"key":"2022111716591004100_bib3","doi-asserted-by":"crossref","first-page":"110352","DOI":"10.1016\/j.biopha.2020.110352","article-title":"A critical review on the relationship of herbal medicine, Akkermansia muciniphila, and human health","volume":"128","author":"Bu","year":"2020","journal-title":"Biomed Pharmacother"},{"key":"2022111716591004100_bib4","doi-asserted-by":"crossref","first-page":"151941","DOI":"10.1016\/j.imbio.2020.151941","article-title":"Dioscin protects against diabetic nephropathy by inhibiting renal inflammation through TLR4\/NF-kappaB pathway in mice","volume":"225","author":"Cai","year":"2020","journal-title":"Immunobiology"},{"key":"2022111716591004100_bib5","doi-asserted-by":"crossref","first-page":"6717212","DOI":"10.1155\/2018\/6717212","article-title":"Hydrogen sulfide attenuates LPS-Induced acute kidney injury by inhibiting inflammation and oxidative stress","volume":"2018","author":"Chen","year":"2018","journal-title":"Oxid Med Cell Longev"},{"key":"2022111716591004100_bib6","doi-asserted-by":"crossref","first-page":"82602","DOI":"10.18632\/oncotarget.13010","article-title":"Hyperin protects against LPS-induced acute kidney injury by inhibiting TLR4 and NLRP3 signaling pathways","volume":"7","author":"Chunzhi","year":"2016","journal-title":"Oncotarget"},{"key":"2022111716591004100_bib7","doi-asserted-by":"crossref","first-page":"e12029","DOI":"10.14814\/phy2.12029","article-title":"Galacto-oligosaccharides attenuate renal injury with microbiota modification","volume":"2","author":"Furuse","year":"2014","journal-title":"Physiol Rep"},{"key":"2022111716591004100_bib8","doi-asserted-by":"crossref","first-page":"38","DOI":"10.3390\/toxins13010038","article-title":"Indoxyl sulfate mediates the low inducibility of the NLRP3 inflammasome in hemodialysis patients","volume":"13","author":"Ho","year":"2021","journal-title":"Toxins"},{"key":"2022111716591004100_bib9","doi-asserted-by":"crossref","first-page":"1781036","DOI":"10.1155\/2018\/1781036","article-title":"Absorption of Codonopsis pilosula saponins by coexisting polysaccharides alleviates gut microbial dysbiosis with dextran sulfate sodium-induced colitis in model mice","volume":"2018","author":"Jing","year":"2018","journal-title":"Biomed Res Int"},{"key":"2022111716591004100_bib10","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1038\/nrneph.2014.91","article-title":"Pattern recognition receptors and the inflammasome in kidney disease","volume":"10","author":"Leemans","year":"2014","journal-title":"Nat Rev Nephrol"},{"key":"2022111716591004100_bib11","doi-asserted-by":"crossref","first-page":"2434","DOI":"10.1161\/CIRCULATIONAHA.115.019645","article-title":"Akkermansia muciniphila protects against atherosclerosis by preventing metabolic endotoxemia-induced inflammation in Apoe-\/- Mice","volume":"133","author":"Li","year":"2016","journal-title":"Circulation"},{"key":"2022111716591004100_bib12","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41418-019-0349-y","article-title":"Exosomal miRNA-19b-3p of tubular epithelial cells promotes M1 macrophage activation in kidney injury","volume":"27","author":"Lv","year":"2020","journal-title":"Cell Death Differentiat"},{"key":"2022111716591004100_bib13","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1038\/s41598-019-40140-5","article-title":"Relative abundance of Akkermansia spp. and other bacterial phylotypes correlates with anxiety- and depressive-like behavior following social defeat in mice","volume":"9","author":"McGaughey","year":"2019","journal-title":"Sci Rep"},{"key":"2022111716591004100_bib14","doi-asserted-by":"crossref","first-page":"759","DOI":"10.1093\/ndt\/gfq818","article-title":"The gut-kidney axis: indoxyl sulfate, p-cresyl sulfate and CKD progression","volume":"26","author":"Meijers","year":"2011","journal-title":"Nephrol Dialysis Transplant"},{"key":"2022111716591004100_bib15","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ejphar.2019.01.062","article-title":"Harmine mitigates LPS-induced acute kidney injury through inhibition of the TLR4-NF-kappaB\/NLRP3 inflammasome signalling pathway in mice","volume":"849","author":"Niu","year":"2019","journal-title":"Eur J Pharmacol"},{"key":"2022111716591004100_bib16","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1111\/sdi.12381","article-title":"The chronic kidney disease - Colonic Axis","volume":"28","author":"Pahl","year":"2015","journal-title":"Semin Dial"},{"key":"2022111716591004100_bib17","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1038\/nm.4236","article-title":"A purified membrane protein from Akkermansia muciniphila or the pasteurized bacterium improves metabolism in obese and diabetic mice","volume":"23","author":"Plovier","year":"2017","journal-title":"Nat Med"},{"key":"2022111716591004100_bib18","doi-asserted-by":"crossref","first-page":"339","DOI":"10.2215\/CJN.07310717","article-title":"Sepsis-Associated AKI","volume":"13","author":"Prowle","year":"2018","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022111716591004100_bib19","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1038\/s41591-018-0128-1","article-title":"Development of a gut microbe-targeted nonlethal therapeutic to inhibit thrombosis potential","volume":"24","author":"Roberts","year":"2018","journal-title":"Nat Med"},{"key":"2022111716591004100_bib20","doi-asserted-by":"crossref","first-page":"e29","DOI":"10.1053\/j.jrn.2012.04.002","article-title":"Foods with added fiber lower serum creatinine levels in patients with chronic kidney disease","volume":"23","author":"Salmean","year":"2013","journal-title":"J Ren Nutr"},{"key":"2022111716591004100_bib21","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1681\/ASN.2019070745","article-title":"A time-updated, parsimonious model to predict AKI in hospitalized children","volume":"31","author":"Sandokji","year":"2020","journal-title":"J Am Soc Nephrol"},{"key":"2022111716591004100_bib22","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.kint.2016.09.040","article-title":"Probiotic supplementation in diabetic hemodialysis patients has beneficial metabolic effects","volume":"91","author":"Soleimani","year":"2017","journal-title":"Kidney Int"},{"key":"2022111716591004100_bib23","doi-asserted-by":"crossref","first-page":"105337","DOI":"10.1016\/j.phrs.2020.105337","article-title":"Enteropeptidase inhibition improves obesity by modulating gut microbiota composition and enterobacterial metabolites in diet-induced obese mice","volume":"163","author":"Sugama","year":"2021","journal-title":"Pharmacol Res"},{"key":"2022111716591004100_bib24","doi-asserted-by":"crossref","first-page":"eabk2709","DOI":"10.1126\/scitranslmed.abk2709","article-title":"Inhibition of METTL3 attenuates renal injury and inflammation by alleviating TAB3 m6A modifications via IGF2BP2-dependent mechanisms","volume":"14","author":"Wang","year":"2022","journal-title":"Sci Transl Med"},{"key":"2022111716591004100_bib25","doi-asserted-by":"crossref","first-page":"101767","DOI":"10.1016\/j.redox.2020.101767","article-title":"The PINK1\/PARK2\/optineurin pathway of mitophagy is activated for protection in septic acute kidney injury","volume":"38","author":"Wang","year":"2021","journal-title":"Redox Biol"},{"key":"2022111716591004100_bib26","doi-asserted-by":"crossref","first-page":"19355","DOI":"10.18632\/oncotarget.8466","article-title":"Distinctly altered gut microbiota in the progression of liver disease","volume":"7","author":"Xie","year":"2016","journal-title":"Oncotarget"},{"key":"2022111716591004100_bib27","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.2215\/CJN.02140215","article-title":"Epidemiology and clinical correlates of AKI in Chinese hospitalized adults","volume":"10","author":"Xu","year":"2015","journal-title":"Clin J Am Soc Nephrol"},{"key":"2022111716591004100_bib28","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1097\/SHK.0000000000001557","article-title":"Sepsis activates the TLR4\/MyD88 pathway in Schwann cells to promote infiltration of macrophages, thereby impeding neuromuscular function","volume":"55","author":"Ye","year":"2021","journal-title":"Shock"},{"key":"2022111716591004100_bib29","article-title":"Dimethyl itaconate alleviates the inflammatory responses of macrophages in sepsis","author":"Zhang","year":"2020","journal-title":"Inflammation"},{"key":"2022111716591004100_bib30","first-page":"3172647","article-title":"CD36-Mediated lipid accumulation and activation of NLRP3 inflammasome lead to podocyte injury in obesity-related glomerulopathy","volume":"2019","author":"Zhao","year":"2019","journal-title":"Mediators Inflamm"},{"key":"2022111716591004100_bib31","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1016\/j.molimm.2020.03.020","article-title":"The roles of NLRP3 inflammasome in bacterial infection","volume":"122","author":"Zhong","year":"2020","journal-title":"Mol Immunol"}],"container-title":["FEMS Microbiology Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/femsle\/advance-article-pdf\/doi\/10.1093\/femsle\/fnac103\/47009288\/fnac103.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/femsle\/article-pdf\/369\/1\/fnac103\/47104284\/fnac103.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/femsle\/article-pdf\/369\/1\/fnac103\/47104284\/fnac103.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,6]],"date-time":"2024-10-06T14:28:10Z","timestamp":1728224890000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/femsle\/article\/doi\/10.1093\/femsle\/fnac103\/6824436"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022]]},"references-count":31,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2022,11,17]]}},"URL":"https:\/\/doi.org\/10.1093\/femsle\/fnac103","relation":{},"ISSN":["1574-6968"],"issn-type":[{"value":"1574-6968","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022]]},"published":{"date-parts":[[2022]]},"article-number":"fnac103"}}