{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:17:46Z","timestamp":1789172266557,"version":"build-2803163510"},"reference-count":77,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.springernature.com\/gp\/researchers\/text-and-data-mining"}],"funder":[{"name":"Noncommunicable Chronic Diseases-NationaScience and Technology Major Project","award":["2023ZD0505200"],"award-info":[{"award-number":["2023ZD0505200"]}]},{"name":"National Natural ScienceFoundation of China","award":["No.82171313,82271338 and 82301492"],"award-info":[{"award-number":["No.82171313,82271338 and 82301492"]}]},{"name":"Joint Funds for the innovation of science and Technology\uff0cFujian province","award":["2023Y9308"],"award-info":[{"award-number":["2023Y9308"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Mol Neurobiol"],"published-print":{"date-parts":[[2026,1]]},"DOI":"10.1007\/s12035-026-06189-w","type":"journal-article","created":{"date-parts":[[2026,9,11]],"date-time":"2026-09-11T11:42:43Z","timestamp":1789126963000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fructooligosaccharides Restore Gut Function and Increase Hippocampal Short-Chain Fatty Acids to Alleviate Neuronal Apoptosis Induced by Mitochondrial Autophagy in rats with Chronic Cerebral Hypoperfusion"],"prefix":"10.1007","volume":"63","author":[{"given":"Junchen","family":"Si","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchao","family":"Fei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyuan","family":"Weng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heng","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinjie","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxiang","family":"Gu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,11]]},"reference":[{"issue":"25","key":"6189_CR1","doi-asserted-by":"publisher","first-page":"3326","DOI":"10.1016\/j.jacc.2019.04.034","volume":"73","author":"C Iadecola","year":"2019","unstructured":"Iadecola C, Duering M, Hachinski V, Joutel A, Pendlebury ST, Schneider JA et al (2019) Vascular cognitive impairment and dementia. J Am Coll Cardiol 73(25):3326\u20133344. https:\/\/doi.org\/10.1016\/j.jacc.2019.04.034","journal-title":"J Am Coll Cardiol"},{"issue":"5","key":"6189_CR2","doi-asserted-by":"publisher","first-page":"3670","DOI":"10.1007\/s12035-016-9915-1","volume":"54","author":"S-Q Du","year":"2016","unstructured":"Du S-Q, Wang X-R, Xiao L-Y, Tu J-F, Zhu W, He T et al (2016) Molecular mechanisms of vascular dementia: what can be learned from animal models of chronic cerebral hypoperfusion? Mol Neurobiol 54(5):3670\u20133682. https:\/\/doi.org\/10.1007\/s12035-016-9915-1","journal-title":"Mol Neurobiol"},{"key":"6189_CR3","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23116224","author":"Z Tian","year":"2022","unstructured":"Tian Z, Ji X, Liu J (2022) Neuroinflammation in vascular cognitive impairment and dementia: current evidence, advances, and prospects. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms23116224","journal-title":"Int J Mol Sci"},{"key":"6189_CR4","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00506-8","author":"L Poh","year":"2022","unstructured":"Poh L, Sim WL, Jo D-G, Dinh QN, Drummond GR, Sobey CG et al (2022) The role of inflammasomes in vascular cognitive impairment. Mol Neurodegener. https:\/\/doi.org\/10.1186\/s13024-021-00506-8","journal-title":"Mol Neurodegener"},{"key":"6189_CR5","doi-asserted-by":"publisher","unstructured":"Venkat P, Chopp M, Chen J. Models and mechanisms of vascular dementia. Exp Neurol. 2015;272:97\u2013108. Epub 20150515. https:\/\/doi.org\/10.1016\/j.expneurol.2015.05.006. PubMed PMID: 25987538; PubMed Central PMCID: PMCPMC4631710.","DOI":"10.1016\/j.expneurol.2015.05.006"},{"key":"6189_CR6","doi-asserted-by":"publisher","unstructured":"Duncombe J, Kitamura A, Hase Y, Ihara M, Kalaria Raj\u00a0N, Horsburgh K. Chronic cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia. Closing the translational gap between rodent models and human vascular cognitive impairment and dementia. Clinical Science. 2017;131(19):2451\u201368. https:\/\/doi.org\/10.1042\/cs20160727.","DOI":"10.1042\/cs20160727"},{"issue":"4","key":"6189_CR7","doi-asserted-by":"publisher","first-page":"1639","DOI":"10.7150\/thno.68304","volume":"12","author":"V Rajeev","year":"2022","unstructured":"Rajeev V, Fann DY, Dinh QN, Kim HA, De Silva TM, Lai MKP et al (2022) Pathophysiology of blood brain barrier dysfunction during chronic cerebral hypoperfusion in vascular cognitive impairment. Theranostics 12(4):1639\u20131658. https:\/\/doi.org\/10.7150\/thno.68304","journal-title":"Theranostics"},{"issue":"4","key":"6189_CR8","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.neuron.2013.10.008","volume":"80","author":"C Iadecola","year":"2013","unstructured":"Iadecola C (2013) The pathobiology of vascular dementia. Neuron 80(4):844\u2013866. https:\/\/doi.org\/10.1016\/j.neuron.2013.10.008","journal-title":"Neuron"},{"key":"6189_CR9","doi-asserted-by":"publisher","unstructured":"Li N, Gu Z, Li Y, Fu X, Wang J, Bai H. A modified bilateral carotid artery stenosis procedure to develop a chronic cerebral hypoperfusion rat model with an increased survival rate. J Neurosci Methods. 2015;255:115\u201321. Epub 20150813. https:\/\/doi.org\/10.1016\/j.jneumeth.2015.08.002. PubMed PMID: 26277419.","DOI":"10.1016\/j.jneumeth.2015.08.002"},{"key":"6189_CR10","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbr.2020.112781","volume":"393","author":"N Hazalin","year":"2020","unstructured":"Hazalin N, Liao P, Hassan Z (2020) TRPM4 inhibition improves spatial memory impairment and hippocampal long-term potentiation deficit in chronic cerebral hypoperfused rats. Behav Brain Res 393:112781. https:\/\/doi.org\/10.1016\/j.bbr.2020.112781","journal-title":"Behav Brain Res"},{"key":"6189_CR11","doi-asserted-by":"publisher","unstructured":"Rajeev V, Chai YL, Poh L, Selvaraji S, Fann DY, Jo D-G, et al. Chronic cerebral hypoperfusion: a critical feature in unravelling the etiology of vascular cognitive impairment. Acta Neuropathologica Communications. 2023;11(1). https:\/\/doi.org\/10.1186\/s40478-023-01590-1.","DOI":"10.1186\/s40478-023-01590-1"},{"key":"6189_CR12","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-021-02250-8","author":"Y Zhao","year":"2021","unstructured":"Zhao Y, Zhang J, Zheng Y, Zhang Y, Zhang XJ, Wang H et al (2021) NAD+ improves cognitive function and reduces neuroinflammation by ameliorating mitochondrial damage and decreasing ROS production in chronic cerebral hypoperfusion models through Sirt1\/PGC-1\u03b1 pathway. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-021-02250-8","journal-title":"J Neuroinflammation"},{"key":"6189_CR13","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-025-03493-5","author":"W Xiao","year":"2025","unstructured":"Xiao W, Yang Y, Bai L, Yang P, Li R, Yang D et al (2025) Exercise-induced irisin ameliorates cognitive impairment following chronic cerebral hypoperfusion by suppressing neuroinflammation and hippocampal neuronal apoptosis. J Neuroinflammation. https:\/\/doi.org\/10.1186\/s12974-025-03493-5","journal-title":"J Neuroinflammation"},{"key":"6189_CR14","doi-asserted-by":"publisher","DOI":"10.1186\/s40478-025-01950-z","author":"Q Yang","year":"2025","unstructured":"Yang Q, Chen Q, Zhang K-B, Liu Y, Zheng J-C, Hu D-X et al (2025) Sinomenine alleviates neuroinflammation in chronic cerebral hypoperfusion by promoting M2 microglial polarization and inhibiting neuronal pyroptosis via exosomal miRNA-223\u20133p. Acta Neuropathol Commun. https:\/\/doi.org\/10.1186\/s40478-025-01950-z","journal-title":"Acta Neuropathol Commun"},{"issue":"2","key":"6189_CR15","doi-asserted-by":"publisher","first-page":"196","DOI":"10.1089\/jmf.2015.3512","volume":"19","author":"M-S Kim","year":"2016","unstructured":"Kim M-S, Bang JH, Lee J, Han J-S, Kang HW, Jeon WK (2016) Fructus mume ethanol extract prevents inflammation and normalizes the septohippocampal cholinergic system in a rat model of chronic cerebral hypoperfusion. J Med Food 19(2):196\u2013204. https:\/\/doi.org\/10.1089\/jmf.2015.3512","journal-title":"J Med Food"},{"key":"6189_CR16","doi-asserted-by":"publisher","unstructured":"Seo JH, Miyamoto N, Hayakawa K, Pham L-DD, Maki T, Ayata C, et al. Oligodendrocyte precursors induce early blood-brain barrier opening after white matter injury. Journal of Clinical Investigation. 2013. https:\/\/doi.org\/10.1172\/jci65863.","DOI":"10.1172\/jci65863"},{"key":"6189_CR17","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2019.104469","author":"S Lautrup","year":"2019","unstructured":"Lautrup S, Lou G, Aman Y, Nilsen H, Tao J, Fang EF (2019) Microglial mitophagy mitigates neuroinflammation in Alzheimer\u2019s disease. Neurochem Int. https:\/\/doi.org\/10.1016\/j.neuint.2019.104469","journal-title":"Neurochem Int"},{"key":"6189_CR18","doi-asserted-by":"publisher","unstructured":"Ouyang M, Zhang Q, Shu J, Wang Z, Fan J, Yu K, et al. Capsaicin ameliorates the loosening of mitochondria-associated endoplasmic reticulum membranes and improves cognitive function in rats with chronic cerebral hypoperfusion. Frontiers in Cellular Neuroscience. 2022;16. https:\/\/doi.org\/10.3389\/fncel.2022.822702.","DOI":"10.3389\/fncel.2022.822702"},{"issue":"2","key":"6189_CR19","doi-asserted-by":"publisher","first-page":"734","DOI":"10.1080\/15548627.2022.2102309","volume":"19","author":"F Li","year":"2022","unstructured":"Li F, Wang Y, Zheng K (2022) Microglial mitophagy integrates the microbiota-gut-brain axis to restrain neuroinflammation during neurotropic herpesvirus infection. Autophagy 19(2):734\u2013736. https:\/\/doi.org\/10.1080\/15548627.2022.2102309","journal-title":"Autophagy"},{"key":"6189_CR20","doi-asserted-by":"publisher","unstructured":"Su S-H, Wu Y-F, Wang D-P, Hai J. Inhibition of excessive autophagy and mitophagy mediates neuroprotective effects of URB597 against chronic cerebral hypoperfusion. Cell Death & Disease. 2018;9(7). https:\/\/doi.org\/10.1038\/s41419-018-0755-y.","DOI":"10.1038\/s41419-018-0755-y"},{"key":"6189_CR21","doi-asserted-by":"publisher","unstructured":"Ahmed H, Leyrolle Q, Koistinen V, K\u00e4rkk\u00e4inen O, Lay\u00e9 S, Delzenne N, et al. Microbiota-derived metabolites as drivers of gut\u2013brain communication. Gut Microbes. 2022;14(1). https:\/\/doi.org\/10.1080\/19490976.2022.2102878.","DOI":"10.1080\/19490976.2022.2102878"},{"key":"6189_CR22","doi-asserted-by":"publisher","DOI":"10.1136\/gpsych-2023-101374","author":"J Cheng","year":"2024","unstructured":"Cheng J, Hu H, Ju Y, Liu J, Wang M, Liu B et al (2024) Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications. Gen Psychiatry (Lond). https:\/\/doi.org\/10.1136\/gpsych-2023-101374","journal-title":"Gen Psychiatry (Lond)"},{"issue":"4","key":"6189_CR23","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1161\/circresaha.119.316448","volume":"127","author":"J Lee","year":"2020","unstructured":"Lee J, d\u2019Aigle J, Atadja L, Quaicoe V, Honarpisheh P, Ganesh BP et al (2020) Gut microbiota\u2013derived short-chain fatty acids promote poststroke recovery in aged mice. Circ Res 127(4):453\u2013465. https:\/\/doi.org\/10.1161\/circresaha.119.316448","journal-title":"Circ Res"},{"key":"6189_CR24","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms6040107","author":"MEM Obrenovich","year":"2018","unstructured":"Obrenovich MEM (2018) Leaky gut, leaky brain? Microorganisms. https:\/\/doi.org\/10.3390\/microorganisms6040107","journal-title":"Microorganisms"},{"issue":"1","key":"6189_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-021-01107-9","volume":"9","author":"Z Zhao","year":"2021","unstructured":"Zhao Z, Ning J, Bao XQ, Shang M, Ma J, Li G et al (2021) Fecal microbiota transplantation protects rotenone-induced Parkinson\u2019s disease mice via suppressing inflammation mediated by the lipopolysaccharide-TLR4 signaling pathway through the microbiota-gut-brain axis. Microbiome 9(1):226. https:\/\/doi.org\/10.1186\/s40168-021-01107-9","journal-title":"Microbiome"},{"key":"6189_CR26","doi-asserted-by":"publisher","unstructured":"Houser MC, Tansey MG. The gut-brain axis: is intestinal inflammation a silent driver of Parkinson\u2019s disease pathogenesis? NPJ Parkinsons Dis. 2017;3:3. Epub 20170111. https:\/\/doi.org\/10.1038\/s41531-016-0002-0. PubMed PMID: 28649603; PubMed Central PMCID: PMCPMC5445611.","DOI":"10.1038\/s41531-016-0002-0"},{"key":"6189_CR27","doi-asserted-by":"publisher","unstructured":"Trigo D, Avelar C, Fernandes M, Sa J, da Cruz ESO. Mitochondria, energy, and metabolism in neuronal health and disease. FEBS Lett. 2022;596(9):1095\u2013110. Epub 20220203. https:\/\/doi.org\/10.1002\/1873-3468.14298. PubMed PMID: 35088449.","DOI":"10.1002\/1873-3468.14298"},{"key":"6189_CR28","doi-asserted-by":"publisher","unstructured":"Qiao L, Yang G, Wang P, Xu C. The potential role of mitochondria in the microbiota-gut-brain axis: Implications for brain health. Pharmacol Res. 2024;209:107434. Epub 20240925. https:\/\/doi.org\/10.1016\/j.phrs.2024.107434. PubMed PMID: 39332752.","DOI":"10.1016\/j.phrs.2024.107434"},{"key":"6189_CR29","doi-asserted-by":"publisher","unstructured":"Xiao W, Su J, Gao X, Yang H, Weng R, Ni W, et al. The microbiota-gut-brain axis participates in chronic cerebral hypoperfusion by disrupting the metabolism of short-chain fatty acids. Microbiome. 2022;10(1). https:\/\/doi.org\/10.1186\/s40168-022-01255-6.","DOI":"10.1186\/s40168-022-01255-6"},{"key":"6189_CR30","doi-asserted-by":"publisher","unstructured":"Erny D, Hrabe de Angelis AL, Jaitin D, Wieghofer P, Staszewski O, David E, et al. Host microbiota constantly control maturation and function of microglia in the CNS. Nat Neurosci. 2015;18(7):965\u201377. Epub 20150601. https:\/\/doi.org\/10.1038\/nn.4030. PubMed PMID: 26030851; PubMed Central PMCID: PMCPMC5528863.","DOI":"10.1038\/nn.4030"},{"key":"6189_CR31","doi-asserted-by":"publisher","unstructured":"Yin X, Duan C, Zhang L, Zhu Y, Qiu Y, Shi K, et al. Microbiota-derived acetate attenuates neuroinflammation in rostral ventrolateral medulla of spontaneously hypertensive rats. J Neuroinflammation. 2024;21(1):101. Epub 20240418. https:\/\/doi.org\/10.1186\/s12974-024-03061-3. PubMed PMID: 38632579; PubMed Central PMCID: PMCPMC11025215.","DOI":"10.1186\/s12974-024-03061-3"},{"key":"6189_CR32","doi-asserted-by":"publisher","unstructured":"Zheng J, An Y, Zhang X, Cao Z, Xu G, Li J, et al. Acetate ameliorates glucolipid metabolic dysregulation and neuroinflammation in diabetic cognitive impairment via enhanced mitophagy. Free Radic Biol Med. 2026;246:580\u201397. Epub 20260130. https:\/\/doi.org\/10.1016\/j.freeradbiomed.2026.01.041. PubMed PMID: 41621600.","DOI":"10.1016\/j.freeradbiomed.2026.01.041"},{"issue":"1","key":"6189_CR33","doi-asserted-by":"publisher","DOI":"10.1186\/s40168-020-00988-6","volume":"9","author":"YF Hou","year":"2021","unstructured":"Hou YF, Shan C, Zhuang SY, Zhuang QQ, Ghosh A, Zhu KC et al (2021) Gut microbiota-derived propionate mediates the neuroprotective effect of osteocalcin in a mouse model of Parkinson\u2019s disease. Microbiome 9(1):34. https:\/\/doi.org\/10.1186\/s40168-020-00988-6","journal-title":"Microbiome"},{"key":"6189_CR34","doi-asserted-by":"publisher","unstructured":"Cheng J, Hu H, Ju Y, Liu J, Wang M, Liu B, et al. Gut microbiota-derived short-chain fatty acids and depression: deep insight into biological mechanisms and potential applications. Gen Psychiatr. 2024;37(1):e101374. Epub 20240219. https:\/\/doi.org\/10.1136\/gpsych-2023-101374. PubMed PMID: 38390241; PubMed Central PMCID: PMCPMC10882305.","DOI":"10.1136\/gpsych-2023-101374"},{"key":"6189_CR35","doi-asserted-by":"publisher","unstructured":"Cho JH, Chae CW, Lim JR, Jung YH, Han SJ, Yoon JH, et al. Sodium butyrate ameliorates high glucose-suppressed neuronal mitophagy by restoring PRKN expression via inhibiting the RELA-HDAC8 complex. Autophagy. 2024;20(7):1505\u201322. Epub 20240306. https:\/\/doi.org\/10.1080\/15548627.2024.2323785. PubMed PMID: 38409852; PubMed Central PMCID: PMCPMC11210903.","DOI":"10.1080\/15548627.2024.2323785"},{"issue":"2","key":"6189_CR36","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1007\/s00253-021-11646-8","volume":"106","author":"MK Yadav","year":"2022","unstructured":"Yadav MK, Kumari I, Singh B, Sharma KK, Tiwari SK (2022) Probiotics, prebiotics and synbiotics: safe options for next-generation therapeutics. Appl Microbiol Biotechnol 106(2):505\u2013521. https:\/\/doi.org\/10.1007\/s00253-021-11646-8","journal-title":"Appl Microbiol Biotechnol"},{"issue":"1","key":"6189_CR37","doi-asserted-by":"publisher","DOI":"10.31083\/IJVNR45457","volume":"96","author":"K Brunelle","year":"2026","unstructured":"Brunelle K, Butler E, Nobles Z, Lewis L, Hernandez S, Koh GY (2026) Fructooligosaccharide upregulates colonic vitamin D receptors and modulates inflammatory status in high-fat diet-induced obese male C57BL\/6 mice. Int J Vitam Nutr Res 96(1):45457. https:\/\/doi.org\/10.31083\/IJVNR45457","journal-title":"Int J Vitam Nutr Res"},{"key":"6189_CR38","doi-asserted-by":"publisher","unstructured":"Paiva IHR, Maciel LM, Silva RSD, Mendonca IP, Souza JRB, Peixoto CA. Prebiotics modulate the microbiota-gut-brain axis and ameliorate anxiety and depression-like behavior in HFD-fed mice. Food Res Int. 2024;182:114153. Epub 20240223. https:\/\/doi.org\/10.1016\/j.foodres.2024.114153. PubMed PMID: 38519181.","DOI":"10.1016\/j.foodres.2024.114153"},{"key":"6189_CR39","doi-asserted-by":"publisher","unstructured":"Li H-Y, Zhou D-D, Gan R-Y, Huang S-Y, Zhao C-N, Shang A, et al. Effects and mechanisms of probiotics, prebiotics, synbiotics, and postbiotics on metabolic diseases targeting gut microbiota: a narrative review. Nutrients. 2021;13(9). https:\/\/doi.org\/10.3390\/nu13093211.","DOI":"10.3390\/nu13093211"},{"key":"6189_CR40","doi-asserted-by":"publisher","unstructured":"Zhao Z, Zhao Y, Dai S, Ge Y, Ye J, Shi R, et al. Fructo-oligosaccharides restore high-fat diet-disrupted diurnal fluctuations in cognitive function in mice via the gut-brain axis. J Agric Food Chem. 2025;73(47):30331\u201344. Epub 20251107. https:\/\/doi.org\/10.1021\/acs.jafc.5c10321. PubMed PMID: 41201833.","DOI":"10.1021\/acs.jafc.5c10321"},{"key":"6189_CR41","doi-asserted-by":"publisher","unstructured":"Li J, Liu F, Luo Y, Wijeyesekera A, Wang S, Chen X, et al. Differential effects of inulin and fructooligosaccharides on gut microbiota composition and glycemic metabolism in overweight\/obese and healthy individuals: a randomized, double-blind clinical trial. BMC Med. 2025;23(1):372. Epub 20250701. https:\/\/doi.org\/10.1186\/s12916-025-04189-6. PubMed PMID: 40598275; PubMed Central PMCID: PMCPMC12219383.","DOI":"10.1186\/s12916-025-04189-6"},{"issue":"5","key":"6189_CR42","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1016\/j.nutres.2008.02.014","volume":"28","author":"ML Stewart","year":"2008","unstructured":"Stewart ML, Timm DA, Slavin JL (2008) Fructooligosaccharides exhibit more rapid fermentation than long-chain inulin in an in vitro fermentation system. Nutr Res 28(5):329\u2013334. https:\/\/doi.org\/10.1016\/j.nutres.2008.02.014","journal-title":"Nutr Res"},{"key":"6189_CR43","doi-asserted-by":"publisher","unstructured":"Burokas A, Arboleya S, Moloney RD, Peterson VL, Murphy K, Clarke G, et al. Targeting the microbiota-gut-brain axis: prebiotics have anxiolytic and antidepressant-like effects and reverse the impact of chronic stress in mice. Biol Psychiatry. 2017;82(7):472\u201387. Epub 20170224. https:\/\/doi.org\/10.1016\/j.biopsych.2016.12.031. PubMed PMID: 28242013.","DOI":"10.1016\/j.biopsych.2016.12.031"},{"key":"6189_CR44","doi-asserted-by":"publisher","unstructured":"Cui S, Guo W, Chen C, Tang X, Zhao J, Mao B et al (2022) Metagenomic analysis of the effects of Lactiplantibacillus plantarum and fructooligosaccharides (FOS) on the fecal microbiota structure in mice. Foods. https:\/\/doi.org\/10.3390\/foods11091187","DOI":"10.3390\/foods11091187"},{"key":"6189_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2021.154767","author":"Z Zhang","year":"2021","unstructured":"Zhang Z, Lin T, Meng Y, Hu M, Shu L, Jiang H et al (2021) FOS\/GOS attenuates high-fat diet induced bone loss via reversing microbiota dysbiosis, high intestinal permeability and systemic inflammation in mice. Metabolism. https:\/\/doi.org\/10.1016\/j.metabol.2021.154767","journal-title":"Metabolism"},{"key":"6189_CR46","doi-asserted-by":"publisher","unstructured":"Zhang YM, Zheng T, Huang TT, Gu PP, Gou LS, Ma TF, et al. Sarsasapogenin attenuates Alzheimer-like encephalopathy in diabetes. Phytomedicine. 2021;91:153686. Epub 20210723. https:\/\/doi.org\/10.1016\/j.phymed.2021.153686. PubMed PMID: 34333330.","DOI":"10.1016\/j.phymed.2021.153686"},{"key":"6189_CR47","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.neuropharm.2018.09.044","volume":"143","author":"C Huang","year":"2018","unstructured":"Huang C, Chu J-T, Liu Y, Chang R-C, Wong G-C (2018) Varenicline reduces DNA damage, tau mislocalization and post surgical cognitive impairment in aged mice. Neuropharmacology 143:217\u201327. https:\/\/doi.org\/10.1016\/j.neuropharm.2018.09.044","journal-title":"Neuropharmacology"},{"issue":"9","key":"6189_CR48","doi-asserted-by":"publisher","first-page":"1741","DOI":"10.1038\/nprot.2012.099","volume":"7","author":"GMJ Beaudoin","year":"2012","unstructured":"Beaudoin GMJ, Lee S-H, Singh D, Yuan Y, Ng Y-G, Reichardt LF et al (2012) Culturing pyramidal neurons from the early postnatal mouse hippocampus and cortex. Nat Protoc 7(9):1741\u20131754. https:\/\/doi.org\/10.1038\/nprot.2012.099","journal-title":"Nat Protoc"},{"key":"6189_CR49","doi-asserted-by":"publisher","unstructured":"He X, Long Q, Zhong Y, Zhang Y, Qian B, Huang S, et al. Short-chain fatty acids regulate erastin-induced cardiomyocyte ferroptosis and ferroptosis-related genes. Frontiers in Pharmacology. 2024;15. https:\/\/doi.org\/10.3389\/fphar.2024.1409321.","DOI":"10.3389\/fphar.2024.1409321"},{"key":"6189_CR50","doi-asserted-by":"publisher","DOI":"10.3390\/cells14221823","author":"C Paciolla","year":"2025","unstructured":"Paciolla C, Manganelli M, Di Chiano M, Montenegro F, Gallone A, Sallustio F et al (2025) Valeric acid: a gut-derived metabolite as a potential epigenetic modulator of neuroinflammation in the gut-brain axis. Cells. https:\/\/doi.org\/10.3390\/cells14221823","journal-title":"Cells"},{"issue":"10","key":"6189_CR51","doi-asserted-by":"publisher","first-page":"4710","DOI":"10.7150\/thno.51739","volume":"11","author":"Y Cai","year":"2021","unstructured":"Cai Y, Liu H, Song E, Wang L, Xu J, He Y et al (2021) Deficiency of telomere-associated repressor activator protein 1 precipitates cardiac aging in mice via p53\/PPAR\u03b1 signaling. Theranostics 11(10):4710\u20134727. https:\/\/doi.org\/10.7150\/thno.51739","journal-title":"Theranostics"},{"issue":"4","key":"6189_CR52","doi-asserted-by":"publisher","first-page":"265","DOI":"10.1038\/nrmicro2538","volume":"9","author":"MA McGuckin","year":"2011","unstructured":"McGuckin MA, Lind\u00e9n SK, Sutton P, Florin TH (2011) Mucin dynamics and enteric pathogens. Nat Rev Microbiol 9(4):265\u2013278. https:\/\/doi.org\/10.1038\/nrmicro2538","journal-title":"Nat Rev Microbiol"},{"issue":"6","key":"6189_CR53","doi-asserted-by":"publisher","first-page":"1924","DOI":"10.1053\/j.gastro.2021.08.047","volume":"161","author":"W-T Kuo","year":"2021","unstructured":"Kuo W-T, Zuo L, Odenwald MA, Madha S, Singh G, Gurniak CB et al (2021) The tight junction protein ZO-1 is dispensable for barrier function but critical for effective mucosal repair. Gastroenterology 161(6):1924\u20131939. https:\/\/doi.org\/10.1053\/j.gastro.2021.08.047","journal-title":"Gastroenterology"},{"issue":"4","key":"6189_CR54","doi-asserted-by":"publisher","first-page":"1633","DOI":"10.1002\/bab.2233","volume":"69","author":"M Asadi","year":"2021","unstructured":"Asadi M, Taghizadeh S, Kaviani E, Vakili O, Taheri\u2010Anganeh M, Tahamtan M et al (2021) Caspase\u20103: structure, function, and biotechnological aspects. Biotechnol Appl Biochem 69(4):1633\u20131645. https:\/\/doi.org\/10.1002\/bab.2233","journal-title":"Biotechnol Appl Biochem"},{"issue":"1","key":"6189_CR55","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1080\/15548627.2022.2062872","volume":"19","author":"Y Zhang","year":"2022","unstructured":"Zhang Y, Fang Q, Wang H, Qi J, Sun S, Liao M et al (2022) Increased mitophagy protects cochlear hair cells from aminoglycoside-induced damage. Autophagy 19(1):75\u201391. https:\/\/doi.org\/10.1080\/15548627.2022.2062872","journal-title":"Autophagy"},{"issue":"8","key":"6189_CR56","doi-asserted-by":"publisher","first-page":"1879","DOI":"10.1080\/15548627.2021.2007027","volume":"18","author":"J Yao","year":"2022","unstructured":"Yao J, Wang J, Xu Y, Guo Q, Sun Y, Liu J et al (2022) CDK9 inhibition blocks the initiation of PINK1-PRKN-mediated mitophagy by regulating the SIRT1-FOXO3-BNIP3 axis and enhances the therapeutic effects involving mitochondrial dysfunction in hepatocellular carcinoma. Autophagy 18(8):1879\u201397. https:\/\/doi.org\/10.1080\/15548627.2021.2007027","journal-title":"Autophagy"},{"issue":"16","key":"6189_CR57","doi-asserted-by":"publisher","first-page":"9082","DOI":"10.1073\/pnas.97.16.9082.PubMedPMID:10922063;PubMedCentralPMCID:PMCPMC16825","volume":"97","author":"RK Bruick","year":"2000","unstructured":"Bruick RK (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 97(16):9082\u20139087. https:\/\/doi.org\/10.1073\/pnas.97.16.9082.PubMedPMID:10922063;PubMedCentralPMCID:PMCPMC16825","journal-title":"Proc Natl Acad Sci U S A"},{"key":"6189_CR58","doi-asserted-by":"publisher","DOI":"10.1186\/s40170-015-0130-8","volume":"3","author":"AH Chourasia","year":"2015","unstructured":"Chourasia AH, Boland ML, Macleod KF (2015) Mitophagy and cancer. Cancer Metab 3:4. https:\/\/doi.org\/10.1186\/s40170-015-0130-8","journal-title":"Cancer Metab"},{"key":"6189_CR59","doi-asserted-by":"publisher","unstructured":"fode T, Giridharan VV, Generoso JS, Bhatti G, Collodel A, Schulz PE, et al. The impact of the microbiota-gut-brain axis on Alzheimer\u2019s disease pathophysiology. Pharmacological Research. 2021;164. https:\/\/doi.org\/10.1016\/j.phrs.2020.105314.","DOI":"10.1016\/j.phrs.2020.105314"},{"key":"6189_CR60","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.ynstr.2017.03.001","volume":"7","author":"JA Foster","year":"2017","unstructured":"Foster JA, Rinaman L, Cryan JF (2017) Stress & the gut-brain axis: regulation by the microbiome. Neurobiol Stress 7:124\u2013136. https:\/\/doi.org\/10.1016\/j.ynstr.2017.03.001","journal-title":"Neurobiol Stress"},{"key":"6189_CR61","doi-asserted-by":"publisher","unstructured":"Chenghan M, Wanxin L, Bangcheng Z, Yao H, Qinxi L, Ting Z, et al. Short-chain fatty acids mediate gut microbiota-brain communication and protect the blood-brain barrier integrity. Ann N Y Acad Sci. 2025;1545(1):116\u201331. Epub 20250225. https:\/\/doi.org\/10.1111\/nyas.15299. PubMed PMID: 39998158.","DOI":"10.1111\/nyas.15299"},{"key":"6189_CR62","doi-asserted-by":"publisher","unstructured":"Su SH, Chen M, Wu YF, Lin Q, Wang DP, Sun J, et al. Fecal microbiota transplantation and short-chain fatty acids protected against cognitive dysfunction in a rat model of chronic cerebral hypoperfusion. CNS Neurosci Ther. 2023;29 Suppl 1(Suppl 1):98\u2013114. Epub 20230110. https:\/\/doi.org\/10.1111\/cns.14089. PubMed PMID: 36627762; PubMed Central PMCID: PMCPMC10314111.","DOI":"10.1111\/cns.14089"},{"key":"6189_CR63","doi-asserted-by":"publisher","unstructured":"Aburto MR, Cryan JF. Gastrointestinal and brain barriers: unlocking gates of communication across the microbiota-gut-brain axis. Nat Rev Gastroenterol Hepatol. 2024;21(4):222\u201347. Epub 20240214. https:\/\/doi.org\/10.1038\/s41575-023-00890-0. PubMed PMID: 38355758.","DOI":"10.1038\/s41575-023-00890-0"},{"key":"6189_CR64","doi-asserted-by":"publisher","unstructured":"Pellegrini C, Fornai M, D\u2019Antongiovanni V, Antonioli L, Bernardini N, Derkinderen P. The intestinal barrier in disorders of the central nervous system. Lancet Gastroenterol Hepatol. 2023;8(1):66\u201380. Epub 20221102. https:\/\/doi.org\/10.1016\/S2468-1253(22)00241-2. PubMed PMID: 36334596.","DOI":"10.1016\/S2468-1253(22)00241-2"},{"key":"6189_CR65","doi-asserted-by":"publisher","DOI":"10.3390\/cells11244038","author":"M Kalyan","year":"2022","unstructured":"Kalyan M, Tousif AH, Sonali S, Vichitra C, Sunanda T, Praveenraj SS et al (2022) Role of endogenous lipopolysaccharides in neurological disorders. Cells. https:\/\/doi.org\/10.3390\/cells11244038","journal-title":"Cells"},{"key":"6189_CR66","doi-asserted-by":"publisher","DOI":"10.3390\/cells15070585","author":"Y Wang","year":"2026","unstructured":"Wang Y, Xie D, Ma S, Wang Y, Zhang C, Chen Z (2026) BNIP3\/BNIP3L-dependent mitophagy protects against hippocampal neuronal damage and apoptosis in a model of vascular dementia. Cells. https:\/\/doi.org\/10.3390\/cells15070585","journal-title":"Cells"},{"key":"6189_CR67","doi-asserted-by":"publisher","unstructured":"Han X, Xu T, Fang Q, Zhang H, Yue L, Hu G, et al. Quercetin hinders microglial activation to alleviate neurotoxicity via the interplay between NLRP3 inflammasome and mitophagy. Redox Biol. 2021;44:102010. Epub 20210525. https:\/\/doi.org\/10.1016\/j.redox.2021.102010. PubMed PMID: 34082381; PubMed Central PMCID: PMCPMC8182123.","DOI":"10.1016\/j.redox.2021.102010"},{"key":"6189_CR68","doi-asserted-by":"publisher","unstructured":"Huo Q, Zhang Y, Zhao J, Bai N, Wang J. HIF-1alpha\/BNIP3-mediated mitophagy mitigates cerebral ischemia\/reperfusion injury in rats by suppressing NLRP3 inflammasome activation. Eur J Med Res. 2026;31(1):251. Epub 20260131. https:\/\/doi.org\/10.1186\/s40001-026-03954-4. PubMed PMID: 41620782; PubMed Central PMCID: PMCPMC12884634.","DOI":"10.1186\/s40001-026-03954-4"},{"key":"6189_CR69","doi-asserted-by":"publisher","unstructured":"Wang L, Peng T, Deng J, Gao W, Wang H, Junhong Luo O, et al. Nicotinamide riboside alleviates brain dysfunction induced by chronic cerebral hypoperfusion via protecting mitochondria. Biochem Pharmacol. 2024;225:116272. Epub 20240507. https:\/\/doi.org\/10.1016\/j.bcp.2024.116272. PubMed PMID: 38723719.","DOI":"10.1016\/j.bcp.2024.116272"},{"key":"6189_CR70","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2023.1138566","volume":"14","author":"Y Wang","year":"2023","unstructured":"Wang Y, Wang Y, Li S, Jin H, Duan J, Lu X et al (2023) Insights of Chinese herbal medicine for mitochondrial dysfunction in chronic cerebral hypoperfusion induced cognitive impairment: existed evidences and potential directions. Front Pharmacol 14:1138566. https:\/\/doi.org\/10.3389\/fphar.2023.1138566","journal-title":"Front Pharmacol"},{"key":"6189_CR71","doi-asserted-by":"publisher","unstructured":"Xiao Q, Liu H, Yang C, Chen Y, Huang Y, Xiao X, et al. Bushen-Yizhi formula exerts neuroprotective effect via inhibiting excessive mitophagy in rats with chronic cerebral hypoperfusion. J Ethnopharmacol. 2023;310:116326. Epub 20230309. https:\/\/doi.org\/10.1016\/j.jep.2023.116326. PubMed PMID: 36898450.","DOI":"10.1016\/j.jep.2023.116326"},{"key":"6189_CR72","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-023-01503-7","author":"S Wang","year":"2023","unstructured":"Wang S, Long H, Hou L, Feng B, Ma Z, Wu Y et al (2023) The mitophagy pathway and its implications in human diseases. Signal Transduct Target Ther. https:\/\/doi.org\/10.1038\/s41392-023-01503-7","journal-title":"Signal Transduct Target Ther"},{"issue":"2","key":"6189_CR73","doi-asserted-by":"publisher","first-page":"736","DOI":"10.7150\/thno.79876","volume":"13","author":"Y Lu","year":"2023","unstructured":"Lu Y, Li Z, Zhang S, Zhang T, Liu Y, Zhang L (2023) Cellular mitophagy: mechanism, roles in diseases and small molecule pharmacological regulation. Theranostics 13(2):736\u2013766. https:\/\/doi.org\/10.7150\/thno.79876","journal-title":"Theranostics"},{"key":"6189_CR74","doi-asserted-by":"publisher","unstructured":"Li J, Wu J, Zhou X, Lu Y, Ge Y, Zhang X. Targeting neuronal mitophagy in ischemic stroke: an update. Burns Trauma. 2023;11:tkad018. Epub 20230531. https:\/\/doi.org\/10.1093\/burnst\/tkad018. PubMed PMID: 37274155; PubMed Central PMCID: PMCPMC10232375.","DOI":"10.1093\/burnst\/tkad018"},{"key":"6189_CR75","doi-asserted-by":"publisher","DOI":"10.3390\/biology14091269","author":"J Wu","year":"2025","unstructured":"Wu J, Liu J, Li Y, Du F, Li W, Thilakavathy K et al (2025) Microglial autophagy and mitophagy in ischemic stroke: from dual roles to therapeutic modulation. Biology (Basel). https:\/\/doi.org\/10.3390\/biology14091269","journal-title":"Biology (Basel)"},{"issue":"5","key":"6189_CR76","doi-asserted-by":"publisher","first-page":"1969","DOI":"10.1042\/bst20221364","volume":"52","author":"NM Niemi","year":"2024","unstructured":"Niemi NM, Friedman JR (2024) Coordinating BNIP3\/NIX-mediated mitophagy in space and time. Biochem Soc Trans 52(5):1969\u20131979. https:\/\/doi.org\/10.1042\/bst20221364","journal-title":"Biochem Soc Trans"},{"key":"6189_CR77","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2024.107434","author":"L Qiao","year":"2024","unstructured":"Qiao L, Yang G, Wang P, Xu C (2024) The potential role of mitochondria in the microbiota-gut-brain axis: implications for brain health. Pharmacol Res. https:\/\/doi.org\/10.1016\/j.phrs.2024.107434","journal-title":"Pharmacol Res"}],"container-title":["Molecular Neurobiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06189-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12035-026-06189-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12035-026-06189-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:03:14Z","timestamp":1789171394000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12035-026-06189-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":77,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["6189"],"URL":"https:\/\/doi.org\/10.1007\/s12035-026-06189-w","relation":{},"ISSN":["0893-7648","1559-1182"],"issn-type":[{"value":"0893-7648","type":"print"},{"value":"1559-1182","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"16 January 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2026","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 September 2026","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"11 September 2026","order":4,"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":"Declarations"}}],"article-number":"888"}}