{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:54:20Z","timestamp":1792040060941,"version":"4.4.0"},"reference-count":67,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T00:00:00Z","timestamp":1774310400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":122,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32270952, 32070583"],"award-info":[{"award-number":["32270952, 32070583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Shanghai Health System Outstanding Talents Program","award":["20234Z0019"],"award-info":[{"award-number":["20234Z0019"]}]},{"DOI":"10.13039\/501100013105","name":"Shanghai Rising-Star Program","doi-asserted-by":"publisher","award":["22QC1400700"],"award-info":[{"award-number":["22QC1400700"]}],"id":[{"id":"10.13039\/501100013105","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["npj Sci Food"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The increasing prevalence of obesity, diabetes, and other metabolic disorders is driving the application of sucralose in the food industry. However, its direct effects on the reproductive function have not been sufficiently investigated. Chronic sucralose consumption may induce ovarian aging, leading to ovarian dysfunction. This occurs in association with intestinal dysbiosis and disruption of intestinal tight junctions caused by prolonged intake of sucralose. These changes increase the production of lipopolysaccharide (LPS), which is derived from gram-negative bacteria, and facilitate its translocation into the systemic circulation. Circulating LPS binds to TLR4 in ovarian granulosa cells, activating the NF-\u03baB signaling pathway. This activation triggers the nuclear translocation of the p65 subunit and increases the transcription of downstream inflammatory cytokines. Moreover, Baicalin methyl ester may serve as an early intervention strategy. It can significantly attenuate both intestinal and ovarian inflammatory damage induced by sucralose, primarily by inhibiting the TLR4\/NF-\u03baB pathway.<\/jats:p>","DOI":"10.1038\/s41538-026-00775-x","type":"journal-article","created":{"date-parts":[[2026,3,24]],"date-time":"2026-03-24T10:33:55Z","timestamp":1774348435000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Long-term sucralose exposure accelerates ovarian aging via gut microbiota dysbiosis"],"prefix":"10.1038","volume":"10","author":[{"given":"Junfeng","family":"Chen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghai","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junjie","family":"Qu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiran","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,24]]},"reference":[{"key":"775_CR1","doi-asserted-by":"publisher","first-page":"3162","DOI":"10.3390\/nu16183162","volume":"16","author":"L Kossiva","year":"2024","unstructured":"Kossiva, L. et al. Chronic use of artificial sweeteners: pros and cons. Nutrients 16, 3162 (2024).","journal-title":"Nutrients"},{"key":"775_CR2","doi-asserted-by":"publisher","first-page":"323","DOI":"10.3390\/life14030323","volume":"14","author":"JA Aguayo-Guerrero","year":"2024","unstructured":"Aguayo-Guerrero, J. A., M\u00e9ndez-Garc\u00eda, L. A., Solleiro-Villavicencio, H., Viurcos-Sanabria, R. & Escobedo, G. Sucralose: from sweet success to metabolic controversies-unraveling the global health implications of a pervasive non-caloric artificial sweetener. Life 14, 323 (2024).","journal-title":"Life"},{"key":"775_CR3","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2024.125517","volume":"366","author":"D Li","year":"2024","unstructured":"Li, D. et al. Accumulation, translocation and transformation of artificial sweeteners in plants: a critical review. Environ. Pollut. 366, 125517 (2024).","journal-title":"Environ. Pollut."},{"key":"775_CR4","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.ajcnut.2024.08.001","volume":"120","author":"AC Sylvetsky","year":"2024","unstructured":"Sylvetsky, A. C. et al. Intergenerational transmission of sucralose and acesulfame-potassium from mothers to their infants via human milk: a pharmacokinetic study. Am. J. Clin. Nutr. 120, 846\u2013853 (2024).","journal-title":"Am. J. Clin. Nutr."},{"key":"775_CR5","doi-asserted-by":"publisher","first-page":"e2126313","DOI":"10.1001\/jamanetworkopen.2021.26313","volume":"4","author":"AG Yunker","year":"2021","unstructured":"Yunker, A. G. et al. Obesity and sex-related associations with differential effects of sucralose vs sucrose on appetite and reward processing: a randomized crossover trial. JAMA Netw. Open 4, e2126313 (2021).","journal-title":"JAMA Netw. Open"},{"key":"775_CR6","doi-asserted-by":"publisher","first-page":"e071204","DOI":"10.1136\/bmj-2022-071204","volume":"378","author":"C Debras","year":"2022","unstructured":"Debras, C. et al. Artificial sweeteners and risk of cardiovascular diseases: results from the prospective NutriNet-Sant\u00e9 cohort. BMJ 378, e071204 (2022).","journal-title":"BMJ"},{"key":"775_CR7","doi-asserted-by":"publisher","first-page":"e1003950","DOI":"10.1371\/journal.pmed.1003950","volume":"19","author":"C Debras","year":"2022","unstructured":"Debras, C. et al. Artificial sweeteners and cancer risk: results from the NutriNet-Sant\u00e9 population-based cohort study. PLoS Med. 19, e1003950 (2022).","journal-title":"PLoS Med."},{"key":"775_CR8","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.2337\/dc23-0206","volume":"46","author":"C Debras","year":"2023","unstructured":"Debras, C. et al. Artificial sweeteners and risk of type 2 diabetes in the prospective NutriNet-Sant\u00e9 cohort. Diab. Care 46, 1681\u20131690 (2023).","journal-title":"Diab. Care"},{"key":"775_CR9","doi-asserted-by":"publisher","first-page":"181","DOI":"10.1038\/nature13793","volume":"514","author":"J Suez","year":"2014","unstructured":"Suez, J. et al. Artificial sweeteners induce glucose intolerance by altering the gut microbiota. Nature 514, 181\u2013186 (2014).","journal-title":"Nature"},{"key":"775_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-11036-9","volume":"10","author":"X Fan","year":"2019","unstructured":"Fan, X. et al. Single-cell reconstruction of follicular remodeling in the human adult ovary. Nat. Commun. 10, 3164 (2019).","journal-title":"Nat. Commun."},{"key":"775_CR11","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1038\/s43587-023-00532-9","volume":"4","author":"Q Yang","year":"2024","unstructured":"Yang, Q. et al. NADase CD38 is a key determinant of ovarian aging. Nat. Aging 4, 110\u2013128 (2024).","journal-title":"Nat. Aging"},{"key":"775_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s40104-023-00948-8","volume":"14","author":"D Xu","year":"2023","unstructured":"Xu, D. et al. Single-cell transcriptomic atlas of goat ovarian aging. J. Anim. Sci. Biotechnol. 14, 151 (2023).","journal-title":"J. Anim. Sci. Biotechnol."},{"key":"775_CR13","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1093\/humupd\/dmaf002","volume":"31","author":"F Zhang","year":"2025","unstructured":"Zhang, F. et al. Harnessing omics data for drug discovery and development in ovarian aging. Hum. Reprod. Update 31, 240\u2013268 (2025).","journal-title":"Hum. Reprod. Update"},{"key":"775_CR14","doi-asserted-by":"publisher","first-page":"418","DOI":"10.1016\/j.tem.2025.01.005","volume":"36","author":"C Wu","year":"2025","unstructured":"Wu, C., Chen, D., Stout, M. B., Wu, M. & Wang, S. Hallmarks of ovarian aging. Trends Endocrinol. Metab. 36, 418\u2013439 (2025).","journal-title":"Trends Endocrinol. Metab."},{"key":"775_CR15","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2023.2295394","volume":"16","author":"F Huang","year":"2024","unstructured":"Huang, F. et al. The influence of the gut microbiome on ovarian aging. Gut Microbes 16, 2295394 (2024).","journal-title":"Gut Microbes"},{"key":"775_CR16","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1210\/er.2009-0006","volume":"30","author":"FJ Broekmans","year":"2009","unstructured":"Broekmans, F. J., Soules, M. R. & Fauser, B. C. Ovarian aging: mechanisms and clinical consequences. Endocr. Rev. 30, 465\u2013493 (2009).","journal-title":"Endocr. Rev."},{"key":"775_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2020.101131","volume":"62","author":"HR Nejabati","year":"2020","unstructured":"Nejabati, H. R. et al. N1-methylnicotinamide: an anti-ovarian aging hormetin? Ageing Res. Rev. 62, 101131 (2020).","journal-title":"Ageing Res. Rev."},{"key":"775_CR18","doi-asserted-by":"publisher","first-page":"695","DOI":"10.3390\/antiox12030695","volume":"12","author":"RJ Reiter","year":"2023","unstructured":"Reiter, R. J. et al. Aging-related ovarian failure and infertility: melatonin to the rescue. Antioxidants 12, 695 (2023).","journal-title":"Antioxidants"},{"key":"775_CR19","doi-asserted-by":"publisher","DOI":"10.1016\/j.envres.2021.111225","volume":"198","author":"FL Zhang","year":"2021","unstructured":"Zhang, F. L. et al. Inflammatory cytokines as key players of apoptosis induced by environmental estrogens in the ovary. Environ. Res. 198, 111225 (2021).","journal-title":"Environ. Res."},{"key":"775_CR20","doi-asserted-by":"publisher","first-page":"771","DOI":"10.1142\/S0192415X25500296","volume":"53","author":"M Jiang","year":"2025","unstructured":"Jiang, M., Li, Z., Qin, X., Chen, L. & Zhu, G. Regulatory role of flavonoid baicalin from Scutellaria baicalensis on AMPK: a review. Am. J. Chin. Med. 53, 771\u2013801 (2025).","journal-title":"Am. J. Chin. Med."},{"key":"775_CR21","doi-asserted-by":"publisher","first-page":"9317","DOI":"10.3390\/ijms24119317","volume":"24","author":"Y Wen","year":"2023","unstructured":"Wen, Y., Wang, Y., Zhao, C., Zhao, B. & Wang, J. The pharmacological efficacy of baicalin in inflammatory diseases. Int. J. Mol. Sci. 24, 9317 (2023).","journal-title":"Int. J. Mol. Sci."},{"key":"775_CR22","doi-asserted-by":"publisher","first-page":"3558","DOI":"10.1002\/ptr.7046","volume":"35","author":"V Baradaran Rahimi","year":"2021","unstructured":"Baradaran Rahimi, V., Askari, V. R. & Hosseinzadeh, H. Promising influences of Scutellaria baicalensis and its two active constituents, baicalin, and baicalein, against metabolic syndrome: a review. Phytother. Res. 35, 3558\u20133574 (2021).","journal-title":"Phytother. Res."},{"key":"775_CR23","doi-asserted-by":"publisher","first-page":"118012","DOI":"10.1016\/j.biopha.2025.118012","volume":"186","author":"M Guo","year":"2025","unstructured":"Guo, M. et al. Baicalin n-butyl ester alleviates inflammatory bowel disease and inhibits pyroptosis through the ROS\/ERK\/P-ERK\/NLRP3 pathway in vivo and in vitro. Biomed. Pharmacother. 186, 118012 (2025).","journal-title":"Biomed. Pharmacother."},{"key":"775_CR24","doi-asserted-by":"publisher","first-page":"5708","DOI":"10.1002\/ptr.7230","volume":"35","author":"B Xu","year":"2021","unstructured":"Xu, B. et al. Synergistic effect of combined treatment with baicalin and emodin on DSS-induced colitis in mouse. Phytother. Res. 35, 5708\u20135719 (2021).","journal-title":"Phytother. Res."},{"key":"775_CR25","doi-asserted-by":"publisher","first-page":"117417","DOI":"10.1016\/j.biopha.2024.117417","volume":"180","author":"M Liang","year":"2024","unstructured":"Liang, M. et al. Baicalin methyl ester prevents the LPS-induced mice intestinal barrier damage in vivo and in vitro via P65\/TNF-\u03b1\/MLCK\/ZO-1 signal pathway. Biomed. Pharmacother. 180, 117417 (2024).","journal-title":"Biomed. Pharmacother."},{"key":"775_CR26","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.fertnstert.2022.10.014","volume":"119","author":"BS Harris","year":"2023","unstructured":"Harris, B. S. et al. Markers of ovarian reserve as predictors of future fertility. Fertil. Steril. 119, 99\u2013106 (2023).","journal-title":"Fertil. Steril."},{"key":"775_CR27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.116046","volume":"304","author":"J Liu","year":"2023","unstructured":"Liu, J. et al. Erxian decoction alleviates cisplatin-induced premature ovarian failure in rats by reducing oxidation levels in ovarian granulosa cells. J. Ethnopharmacol. 304, 116046 (2023).","journal-title":"J. Ethnopharmacol."},{"key":"775_CR28","doi-asserted-by":"publisher","DOI":"10.1016\/j.psj.2020.12.056","volume":"100","author":"SJ Huang","year":"2021","unstructured":"Huang, S. J. et al. Effect of anti-m\u00fcllerian hormone on the development and selection of ovarian follicle in hens. Poult. Sci. 100, 100959 (2021).","journal-title":"Poult. Sci."},{"key":"775_CR29","doi-asserted-by":"publisher","DOI":"10.1016\/j.envpol.2022.120662","volume":"316","author":"QK He","year":"2023","unstructured":"He, Q. K. et al. 3-MCPD exposure enhances ovarian fibrosis and reduces oocyte quality in mice. Environ. Pollut. 316, 120662 (2023).","journal-title":"Environ. Pollut."},{"key":"775_CR30","doi-asserted-by":"publisher","first-page":"856","DOI":"10.1017\/S0007114519001570","volume":"122","author":"P Thomson","year":"2019","unstructured":"Thomson, P., Santiba\u00f1ez, R., Aguirre, C., Galgani, J. E. & Garrido, D. Short-term impact of sucralose consumption on the metabolic response and gut microbiome of healthy adults. Br. J. Nutr. 122, 856\u2013862 (2019).","journal-title":"Br. J. Nutr."},{"key":"775_CR31","doi-asserted-by":"publisher","first-page":"S31","DOI":"10.1093\/advances\/nmy037","volume":"10","author":"FJ Ruiz-Ojeda","year":"2019","unstructured":"Ruiz-Ojeda, F. J., Plaza-D\u00edaz, J., S\u00e1ez-Lara, M. J. & Gil, A. Effects of sweeteners on the gut microbiota: a review of experimental studies and clinical trials. Adv. Nutr. 10, S31\u2013s48 (2019).","journal-title":"Adv. Nutr."},{"key":"775_CR32","doi-asserted-by":"publisher","first-page":"984","DOI":"10.1016\/j.molimm.2006.03.013","volume":"44","author":"Y Yang","year":"2007","unstructured":"Yang, Y. et al. Lipopolysaccharide (LPS) regulates TLR4 signal transduction in nasopharynx epithelial cell line 5-8F via NFkappaB and MAPKs signaling pathways. Mol. Immunol. 44, 984\u2013992 (2007).","journal-title":"Mol. Immunol."},{"key":"775_CR33","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s10753-016-0447-7","volume":"40","author":"JL Lai","year":"2017","unstructured":"Lai, J. L. et al. Indirubin inhibits LPS-induced inflammation via TLR4 abrogation mediated by the NF-kB and MAPK signaling pathways. Inflammation 40, 1\u201312 (2017).","journal-title":"Inflammation"},{"key":"775_CR34","doi-asserted-by":"publisher","first-page":"1077","DOI":"10.1007\/s10753-023-01793-7","volume":"46","author":"M Zhang","year":"2023","unstructured":"Zhang, M. et al. E. coli LPS\/TLR4\/NF-\u03baB signaling pathway regulates Th17\/Treg balance mediating inflammatory responses in oral lichen planus. Inflammation 46, 1077\u20131090 (2023).","journal-title":"Inflammation"},{"key":"775_CR35","doi-asserted-by":"publisher","first-page":"1873","DOI":"10.3390\/molecules28041873","volume":"28","author":"B Shen","year":"2023","unstructured":"Shen, B. et al. Baicalin relieves LPS-induced lung inflammation via the NF-\u03baB and MAPK pathways. Molecules 28, 1873 (2023).","journal-title":"Molecules"},{"key":"775_CR36","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1474-8","volume":"16","author":"LT Guo","year":"2019","unstructured":"Guo, L. T. et al. Baicalin ameliorates neuroinflammation-induced depressive-like behavior through inhibition of toll-like receptor 4 expression via the PI3K\/AKT\/FoxO1 pathway. J. Neuroinflammation 16, 95 (2019).","journal-title":"J. Neuroinflammation"},{"key":"775_CR37","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2021.107725","volume":"96","author":"X Wang","year":"2021","unstructured":"Wang, X. et al. Baicalin protects LPS-induced blood-brain barrier damage and activates Nrf2-mediated antioxidant stress pathway. Int. Immunopharmacol. 96, 107725 (2021).","journal-title":"Int. Immunopharmacol."},{"key":"775_CR38","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2023.e22079","volume":"9","author":"X Li","year":"2023","unstructured":"Li, X., Yue, J., Kumar, Y. & Ma, Y. Chemoprotective effect of baicalin against cyclophosphamide induced ovarian toxicity in mice via inhibition of TGF-\u03b2. Heliyon 9, e22079 (2023).","journal-title":"Heliyon"},{"key":"775_CR39","doi-asserted-by":"publisher","first-page":"878","DOI":"10.1080\/13880209.2023.2208636","volume":"61","author":"X Xu","year":"2023","unstructured":"Xu, X., Xu, X., Wang, X. & Shen, L. Baicalin suppress the development of polycystic ovary syndrome via regulating the miR-874-3p\/FOXO3 and miR-144\/FOXO1 axis. Pharm. Biol. 61, 878\u2013885 (2023).","journal-title":"Pharm. Biol."},{"key":"775_CR40","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12906-024-04346-z","volume":"24","author":"J Chen","year":"2024","unstructured":"Chen, J., Lin, C., Huang, X. & Bian, W. Baicalin enhances proliferation and reduces inflammatory-oxidative stress effect in H(2)O(2)-induced granulosa cells apoptosis via USP48 protein regulation. BMC Complement. Med. Ther. 24, 42 (2024).","journal-title":"BMC Complement. Med. Ther."},{"key":"775_CR41","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.823723","volume":"9","author":"HT Wu","year":"2022","unstructured":"Wu, H. T. et al. Sucralose, a non-nutritive artificial sweetener exacerbates high fat diet-induced hepatic steatosis through taste receptor type 1 member 3. Front. Nutr. 9, 823723 (2022).","journal-title":"Front. Nutr."},{"key":"775_CR42","doi-asserted-by":"publisher","first-page":"8535","DOI":"10.1039\/D1FO01160J","volume":"12","author":"P Zafrilla","year":"2021","unstructured":"Zafrilla, P., Masoodi, H., Cerd\u00e1, B. & Garc\u00eda-Viguera, C. Villa\u00f1o D: biological effects of stevia, sucralose and sucrose in citrus-maqui juices on overweight subjects. Food Funct. 12, 8535\u20138543 (2021).","journal-title":"Food Funct."},{"key":"775_CR43","doi-asserted-by":"publisher","first-page":"1500","DOI":"10.1093\/advances\/nmaa185","volume":"12","author":"S Risdon","year":"2021","unstructured":"Risdon, S. et al. Sucralose and cardiometabolic health: current understanding from receptors to clinical investigations. Adv. Nutr. 12, 1500\u20131513 (2021).","journal-title":"Adv. Nutr."},{"key":"775_CR44","doi-asserted-by":"publisher","DOI":"10.1016\/j.reprotox.2024.108644","volume":"128","author":"L Yang","year":"2024","unstructured":"Yang, L. et al. Sucralose triggers insulin resistance leading to follicular dysplasia in mice. Reprod. Toxicol. 128, 108644 (2024).","journal-title":"Reprod. Toxicol."},{"key":"775_CR45","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/j.mucimm.2023.01.006","volume":"16","author":"M Sylvestre","year":"2023","unstructured":"Sylvestre, M., Di Carlo, S. E. & Peduto, L. Stromal regulation of the intestinal barrier. Mucosal Immunol. 16, 221\u2013231 (2023).","journal-title":"Mucosal Immunol."},{"key":"775_CR46","doi-asserted-by":"publisher","first-page":"2754","DOI":"10.1021\/acs.jafc.9b00080","volume":"67","author":"Y Cui","year":"2019","unstructured":"Cui, Y., Wang, Q., Chang, R., Zhou, X. & Xu, C. Intestinal barrier function-non-alcoholic fatty liver disease interactions and possible role of gut microbiota. J. Agric. Food Chem. 67, 2754\u20132762 (2019).","journal-title":"J. Agric. Food Chem."},{"key":"775_CR47","doi-asserted-by":"publisher","DOI":"10.1016\/j.redox.2022.102528","volume":"58","author":"A Brandt","year":"2022","unstructured":"Brandt, A. et al. Impairments of intestinal arginine and NO metabolisms trigger aging-associated intestinal barrier dysfunction and \u2018inflammaging\u2019. Redox Biol. 58, 102528 (2022).","journal-title":"Redox Biol."},{"key":"775_CR48","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1146\/annurev.immunol.14.1.649","volume":"14","author":"AS Baldwin Jr.","year":"1996","unstructured":"Baldwin, A. S. Jr. The NF-kappa B and I kappa B proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649\u2013683 (1996).","journal-title":"Annu. Rev. Immunol."},{"key":"775_CR49","doi-asserted-by":"publisher","first-page":"768","DOI":"10.1016\/j.tig.2019.07.009","volume":"35","author":"J Chen","year":"2019","unstructured":"Chen, J. & Stark, L. A. Insights into the relationship between nucleolar stress and the NF-\u03baB pathway. Trends Genet. 35, 768\u2013780 (2019).","journal-title":"Trends Genet."},{"key":"775_CR50","doi-asserted-by":"publisher","first-page":"407","DOI":"10.2147\/JIR.S140188","volume":"11","author":"S Giridharan","year":"2018","unstructured":"Giridharan, S. & Srinivasan, M. Mechanisms of NF-\u03baB p65 and strategies for therapeutic manipulation. J. Inflamm. Res. 11, 407\u2013419 (2018).","journal-title":"J. Inflamm. Res."},{"key":"775_CR51","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1016\/j.tibs.2004.11.009","volume":"30","author":"P Viatour","year":"2005","unstructured":"Viatour, P., Merville, M. P., Bours, V. & Chariot, A. Phosphorylation of NF-kappaB and IkappaB proteins: implications in cancer and inflammation. Trends Biochem. Sci. 30, 43\u201352 (2005).","journal-title":"Trends Biochem. Sci."},{"key":"775_CR52","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2021.109568","volume":"345","author":"KS Alharbi","year":"2021","unstructured":"Alharbi, K. S. et al. Nuclear factor-kappa B and its role in inflammatory lung disease. Chem. Biol. Interact. 345, 109568 (2021).","journal-title":"Chem. Biol. Interact."},{"key":"775_CR53","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3390\/antiox14010039","volume":"14","author":"M Ahmed","year":"2024","unstructured":"Ahmed, M. et al. Nicotinamide mononucleotide restores NAD(+) levels to alleviate LPS-induced inflammation via the TLR4\/NF-\u03baB\/MAPK signaling pathway in mice granulosa cells. Antioxidants 14, 39 (2024).","journal-title":"Antioxidants"},{"key":"775_CR54","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2024.118274","volume":"331","author":"HR Guan","year":"2024","unstructured":"Guan, H. R. et al. Exploring the efficacy and mechanism of Bailing capsule to improve polycystic ovary syndrome in mice based on intestinal-derived LPS-TLR4 pathway. J. Ethnopharmacol. 331, 118274 (2024).","journal-title":"J. Ethnopharmacol."},{"key":"775_CR55","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2024.135844","volume":"280","author":"H Zhang","year":"2024","unstructured":"Zhang, H. et al. Cordyceps polysaccharide improves polycystic ovary syndrome by inhibiting gut-derived LPS\/TLR4 pathway to attenuates insulin resistance. Int. J. Biol. Macromol. 280, 135844 (2024).","journal-title":"Int. J. Biol. Macromol."},{"key":"775_CR56","doi-asserted-by":"publisher","unstructured":"Chiang, Y. F., Chen, Y. C., Huang, K. C., Ali, M. & Hsia, S. M. Exposure to sucralose and its effects on testicular damageand male infertility: insights into oxidative stress and autophagy. Environ. Health Perspect. https:\/\/doi.org\/10.1289\/EHP15919 (2025).","DOI":"10.1289\/EHP15919"},{"key":"775_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.scitotenv.2023.169603","volume":"919","author":"L Chi","year":"2024","unstructured":"Chi, L. et al. Chronic sucralose consumption inhibits farnesoid X receptor signaling and perturbs lipid and cholesterol homeostasis in the mouse livers, potentially by altering gut microbiota functions. Sci. Total Environ. 919, 169603 (2024).","journal-title":"Sci. Total Environ."},{"key":"775_CR58","doi-asserted-by":"publisher","first-page":"1043","DOI":"10.1080\/19490976.2020.1738187","volume":"11","author":"X Dai","year":"2020","unstructured":"Dai, X. et al. Maternal sucralose intake alters gut microbiota of offspring and exacerbates hepatic steatosis in adulthood. Gut Microbes 11, 1043\u20131063 (2020).","journal-title":"Gut Microbes"},{"key":"775_CR59","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2021.711055","volume":"11","author":"SC Bokoliya","year":"2021","unstructured":"Bokoliya, S. C., Dorsett, Y., Panier, H. & Zhou, Y. Procedures for fecal microbiota transplantation in murine microbiome studies. Front. Cell. Infect. Microbiol. 11, 711055 (2021).","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"775_CR60","doi-asserted-by":"publisher","first-page":"1132","DOI":"10.4014\/jmb.2002.02044","volume":"30","author":"W Zhang","year":"2020","unstructured":"Zhang, W. et al. Fecal microbiota transplantation (FMT) alleviates experimental colitis in mice by gut microbiota regulation. J. Microbiol. Biotechnol. 30, 1132\u20131141 (2020).","journal-title":"J. Microbiol. Biotechnol."},{"key":"775_CR61","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01007-y","volume":"9","author":"Y Jing","year":"2021","unstructured":"Jing, Y. et al. Effect of fecal microbiota transplantation on neurological restoration in a spinal cord injury mouse model: involvement of brain-gut axis. Microbiome 9, 59 (2021).","journal-title":"Microbiome"},{"key":"775_CR62","doi-asserted-by":"publisher","DOI":"10.1080\/19490976.2024.2383353","volume":"16","author":"H Jiang","year":"2024","unstructured":"Jiang, H. et al. The fecal microbiota of patients with primary biliary cholangitis (PBC) causes PBC-like liver lesions in mice and exacerbates liver damage in a mouse model of PBC. Gut Microbes 16, 2383353 (2024).","journal-title":"Gut Microbes"},{"key":"775_CR63","doi-asserted-by":"publisher","first-page":"996","DOI":"10.1038\/nmeth.2604","volume":"10","author":"RC Edgar","year":"2013","unstructured":"Edgar, R. C. UPARSE: highly accurate OTU sequences from microbial amplicon reads. Nat. Methods 10, 996\u2013998 (2013).","journal-title":"Nat. Methods"},{"key":"775_CR64","doi-asserted-by":"publisher","first-page":"5261","DOI":"10.1128\/AEM.00062-07","volume":"73","author":"Q Wang","year":"2007","unstructured":"Wang, Q., Garrity, G. M., Tiedje, J. M. & Cole, J. R. Naive Bayesian classifier for rapid assignment of rRNA sequences into the new bacterial taxonomy. Appl. Environ. Microbiol. 73, 5261\u20135267 (2007).","journal-title":"Appl. Environ. Microbiol."},{"key":"775_CR65","doi-asserted-by":"publisher","first-page":"3146","DOI":"10.1210\/en.2014-1196","volume":"155","author":"AS Caldwell","year":"2014","unstructured":"Caldwell, A. S. et al. Characterization of reproductive, metabolic, and endocrine features of polycystic ovary syndrome in female hyperandrogenic mouse models. Endocrinology 155, 3146\u20133159 (2014).","journal-title":"Endocrinology"},{"key":"775_CR66","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41387-022-00230-2","volume":"13","author":"LM Voetmann","year":"2023","unstructured":"Voetmann, L. M., Rolin, B., Kirk, R. K., Pyke, C. & Hansen, A. K. The intestinal permeability marker FITC-dextran 4kDa should be dosed according to lean body mass in obese mice. Nutr. Diab. 13, 1 (2023).","journal-title":"Nutr. Diab."},{"key":"775_CR67","doi-asserted-by":"publisher","DOI":"10.1016\/j.jep.2022.115919","volume":"302","author":"X Wang","year":"2023","unstructured":"Wang, X. et al. Gegen Qinlian decoction activates AhR\/IL-22 to repair intestinal barrier by modulating gut microbiota-related tryptophan metabolism in ulcerative colitis mice. J. Ethnopharmacol. 302, 115919 (2023).","journal-title":"J. Ethnopharmacol."}],"container-title":["npj Science of Food"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00775-x","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00775-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00775-x.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:01:39Z","timestamp":1784898099000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41538-026-00775-x"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,24]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["775"],"URL":"https:\/\/doi.org\/10.1038\/s41538-026-00775-x","relation":{},"ISSN":["2396-8370"],"issn-type":[{"value":"2396-8370","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,24]]},"assertion":[{"value":"16 September 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 February 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}],"article-number":"229"}}