{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:15:40Z","timestamp":1792790140056,"version":"4.5.0"},"reference-count":184,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"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":["82560898"],"award-info":[{"award-number":["82560898"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82060831"],"award-info":[{"award-number":["82060831"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Alzheimer\u2019s disease (AD) represents an increasingly severe global health challenge. Recently, the role of the gut\u2013brain axis in AD pathogenesis has garnered significant attention. Dysbiosis of the gut microbiota can exacerbate core pathologies such as neuroinflammation, amyloid beta (A\u03b2) deposition, and tau hyperphosphorylation through neural, endocrine, and immune pathways. Polyphenolic compounds have emerged as a focal point in neuroprotective research owing to their pronounced anti-inflammatory and antioxidant properties. Notably, polyphenols exert effects not only by directly influencing the central nervous system (CNS) but also through indirectly modulating the composition and function of the gut microbiota, thereby impacting bidirectional gut\u2013brain communication. This dual mechanism offers a potential avenue for their application in the prevention and treatment of AD. This review aims to compile recent research on the relationship between polyphenols and the gut microbiota. We assessed the literature from PubMed, Google Scholar, and Web of Science databases, published from the establishment of the database to 24 November 2025. The keywords used include \u201cPolyphenols\u201d, \u201cGut\u2013brain axis\u201d, \u201cGut microbiota\u201d, \u201cAlzheimer\u2019s disease\u201d, \u201cEpigallocatechin gallate\u201d, \u201cQuercetin\u201d, \u201cCurcumin\u201d, \u201cFerulic acid\u201d, \u201cResveratrol\u201d, \u201cAnthocyanin\u201d, \u201cMyricetin\u201d, \u201cChlorogenic acid\u201d, etc. This review discusses the various mechanisms by which polyphenols influence AD through modulating the gut microbiota. Polyphenols and gut microbiota exhibit critical bidirectional interactions. On one hand, the bioavailability and activity of polyphenols are highly dependent on metabolic conversion by gut microbiota. On the other hand, polyphenols selectively promote the proliferation of beneficial bacteria such as bifidobacteria and lactobacilli like prebiotics, while inhibiting the growth of pathogenic bacteria. This reshapes the intestinal microecology, enhances barrier function, and regulates beneficial metabolites. Utilizing a nanotechnology-based drug delivery system, the pharmacokinetic stability and brain targeting efficacy of polyphenols can be significantly enhanced, providing innovative opportunities for the targeted prevention and management of AD.<\/jats:p>","DOI":"10.3390\/ijms27020604","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"604","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Targeting the Gut Microbiota: Mechanistic Investigation of Polyphenol Modulation of the Gut\u2013Brain Axis in Alzheimer\u2019s Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Zhenning","family":"Wang","sequence":"first","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Ba","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man","family":"Li","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanyuan","family":"Wei","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuenan","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqin","family":"Mao","sequence":"additional","affiliation":[{"name":"First Clinical Medical College, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Xiang","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongdong","family":"Qin","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chuhua","family":"Zeng","sequence":"additional","affiliation":[{"name":"School of Basic Medicine, Yunnan University of Chinese Medicine, Kunming 650500, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"(2024). 2024 Alzheimer\u2019s disease facts and figures. Alzheimers Dement., 20, 3708\u20133821.","DOI":"10.1002\/alz.13809"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e32489","DOI":"10.2196\/32489","article-title":"Perceptions of Cognitive Training Games and Assessment Technologies for Dementia: Acceptability Study with Patient and Public Involvement Workshops","volume":"10","author":"Harrington","year":"2022","journal-title":"JMIR Serious Games"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1038\/s41572-021-00269-y","article-title":"Alzheimer disease","volume":"7","author":"Knopman","year":"2021","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.pharmthera.2015.11.012","article-title":"Gut microbiome in health and disease: Linking the microbiome-gut-brain axis and environmental factors in the pathogenesis of systemic and neurodegenerative diseases","volume":"158","author":"Ghaisas","year":"2016","journal-title":"Pharmacol. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1016\/j.chom.2019.07.008","article-title":"The Landscape of Genetic Content in the Gut and Oral Human Microbiome","volume":"26","author":"Tierney","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"105840","DOI":"10.1016\/j.phrs.2021.105840","article-title":"The role of microbiota-gut-brain axis in neuropsychiatric and neurological disorders","volume":"172","author":"Doboszewska","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1016\/bs.ant.2024.02.003","article-title":"Utility of zebrafish-based models in understanding molecular mechanisms of neurotoxicity mediated by the gut-brain axis","volume":"11","author":"Adedara","year":"2024","journal-title":"Adv. Neurotoxicol."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Roberts, J.D., Lillis, J., Pinto, J.M., Willmott, A.G.B., Gautam, L., Davies, C., L\u00f3pez-Samanes, \u00c1., Del Coso, J., and Chichger, H. (2022). The Impact of a Natural Olive-Derived Phytocomplex (OliPhenolia(\u00ae)) on Exercise-Induced Oxidative Stress in Healthy Adults. Nutrients, 14.","DOI":"10.3390\/nu14235156"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Grabska-Koby\u0142ecka, I., Szpakowski, P., Kr\u00f3l, A., Ksi\u0105\u017cek-Winiarek, D., Koby\u0142ecki, A., G\u0142\u0105bi\u0144ski, A., and Nowak, D. (2023). Polyphenols and Their Impact on the Prevention of Neurodegenerative Diseases and Development. Nutrients, 15.","DOI":"10.3390\/nu15153454"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"3421","DOI":"10.1080\/10408398.2020.1865870","article-title":"Polyphenols and neurodegenerative diseases: Focus on neuronal regeneration","volume":"62","author":"Moradi","year":"2022","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1093\/gerona\/gly166","article-title":"Polyphenols From Grape and Blueberry Improve Episodic Memory in Healthy Elderly with Lower Level of Memory Performance: A Bicentric Double-Blind, Randomized, Placebo-Controlled Clinical Study","volume":"74","author":"Bensalem","year":"2019","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Zhang, Y., Yu, W., Zhang, L., Wang, M., and Chang, W. (2022). The Interaction of Polyphenols and the Gut Microbiota in Neurodegenerative Diseases. Nutrients, 14.","DOI":"10.3390\/nu14245373"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Li, Z., Zhao, T., Shi, M., Wei, Y., Huang, X., Shen, J., Zhang, X., Xie, Z., Huang, P., and Yuan, K. (2023). Polyphenols: Natural food grade biomolecules for treating neurodegenerative diseases from a multi-target perspective. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1139558"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Wu, X., Zhou, Y., Xi, Y., Zhou, H., Tang, Z., Xiong, L., and Qin, D. (2024). Polyphenols: Natural Food-Grade Biomolecules for the Treatment of Nervous System Diseases from a Multi-Target Perspective. Pharmaceuticals, 17.","DOI":"10.20944\/preprints202405.1673.v1"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"G\u00f3ralczyk-Bi\u0144kowska, A., Szmajda-Krygier, D., and Koz\u0142owska, E. (2022). The Microbiota-Gut-Brain Axis in Psychiatric Disorders. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231911245"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"aaw9255","DOI":"10.1126\/science.aaw9255","article-title":"Vulnerability of the industrialized microbiota","volume":"366","author":"Sonnenburg","year":"2019","journal-title":"Science"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4209","DOI":"10.1113\/JP279919","article-title":"Intra-gastrointestinal amyloid-\u03b21-42 oligomers perturb enteric function and induce Alzheimer\u2019s disease pathology","volume":"598","author":"Sun","year":"2020","journal-title":"J. Physiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2271613","DOI":"10.1080\/19490976.2023.2271613","article-title":"Gut microbiome-targeted therapies for Alzheimer\u2019s disease","volume":"15","author":"Zhang","year":"2023","journal-title":"Gut Microbes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1210\/me.2014-1108","article-title":"Minireview: Gut microbiota: The neglected endocrine organ","volume":"28","author":"Clarke","year":"2014","journal-title":"Mol. Endocrinol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1113\/JP273106","article-title":"Gut instincts: Microbiota as a key regulator of brain development, ageing and neurodegeneration","volume":"595","author":"Dinan","year":"2017","journal-title":"J. Physiol."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Otaru, N., Ye, K., Mujezinovic, D., Berchtold, L., Constancias, F., Cornejo, F.A., Krzystek, A., de Wouters, T., Braegger, C., and Lacroix, C. (2021). GABA Production by Human Intestinal Bacteroides spp.: Prevalence, Regulation, and Role in Acid Stress Tolerance. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.656895"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.anaerobe.2016.10.011","article-title":"GABA production and structure of gadB\/gadC genes in Lactobacillus and Bifidobacterium strains from human microbiota","volume":"42","author":"Yunes","year":"2016","journal-title":"Anaerobe"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1464","DOI":"10.1056\/NEJM199205283262204","article-title":"Decreased glutamate transport by the brain and spinal cord in amyotrophic lateral sclerosis","volume":"326","author":"Rothstein","year":"1992","journal-title":"N. Engl. J. Med."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"5025","DOI":"10.1038\/s41380-023-02140-w","article-title":"The GABAergic system in Alzheimer\u2019s disease: A systematic review with meta-analysis","volume":"28","author":"Bellaver","year":"2023","journal-title":"Mol. Psychiatry"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.cell.2012.02.046","article-title":"Inhibitory interneuron deficit links altered network activity and cognitive dysfunction in Alzheimer model","volume":"149","author":"Verret","year":"2012","journal-title":"Cell"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"488","DOI":"10.1111\/gbb.12133","article-title":"Abnormal vibrissa-related behavior and loss of barrel field inhibitory neurons in 5xFAD transgenics","volume":"13","author":"Flanigan","year":"2014","journal-title":"Genes Brain Behav."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/nrn.2016.141","article-title":"Network abnormalities and interneuron dysfunction in Alzheimer disease","volume":"17","author":"Palop","year":"2016","journal-title":"Nat. Rev. Neurosci."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Kiriyama, Y., and Nochi, H. (2019). The Biosynthesis, Signaling, and Neurological Functions of Bile Acids. Biomolecules, 9.","DOI":"10.3390\/biom9060232"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1016\/j.dld.2014.01.159","article-title":"Bile acids permeabilize the blood brain barrier after bile duct ligation in rats via Rac1-dependent mechanisms","volume":"46","author":"Quinn","year":"2014","journal-title":"Dig. Liver Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1111\/j.1749-6632.2012.06513.x","article-title":"The link between altered cholesterol metabolism and Alzheimer\u2019s disease","volume":"1259","author":"Gamba","year":"2012","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Du, Y., He, C., An, Y., Huang, Y., Zhang, H., Fu, W., Wang, M., Shan, Z., Xie, J., and Yang, Y. (2024). The Role of Short Chain Fatty Acids in Inflammation and Body Health. Int. J. Mol. Sci., 25.","DOI":"10.3390\/ijms25137379"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.mib.2012.12.001","article-title":"Microbial amyloids--functions and interactions within the host","volume":"16","author":"Schwartz","year":"2013","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"35092","DOI":"10.1074\/jbc.M112.383737","article-title":"Promiscuous cross-seeding between bacterial amyloids promotes interspecies biofilms","volume":"287","author":"Zhou","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Bonaz, B., Bazin, T., and Pellissier, S. (2018). The Vagus Nerve at the Interface of the Microbiota-Gut-Brain Axis. Front. Neurosci., 12.","DOI":"10.3389\/fnins.2018.00049"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5026","DOI":"10.1007\/s12035-020-02073-3","article-title":"Gut Microbiota and Dysbiosis in Alzheimer\u2019s Disease: Implications for Pathogenesis and Treatment","volume":"57","author":"Liu","year":"2020","journal-title":"Mol. Neurobiol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"16050","DOI":"10.1073\/pnas.1102999108","article-title":"Ingestion of Lactobacillus strain regulates emotional behavior and central GABA receptor expression in a mouse via the vagus nerve","volume":"108","author":"Bravo","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.euroneuro.2017.12.004","article-title":"The vagus nerve modulates BDNF expression and neurogenesis in the hippocampus","volume":"28","author":"Ogbonnaya","year":"2018","journal-title":"Eur. Neuropsychopharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1053\/j.gastro.2020.10.066","article-title":"The Microbiota-Gut-Brain Axis: From Motility to Mood","volume":"160","author":"Margolis","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1877","DOI":"10.1152\/physrev.00018.2018","article-title":"The Microbiota-Gut-Brain Axis","volume":"99","author":"Cryan","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"eaat5236","DOI":"10.1126\/science.aat5236","article-title":"A gut-brain neural circuit for nutrient sensory transduction","volume":"361","author":"Kaelberer","year":"2018","journal-title":"Science"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"e147700","DOI":"10.1172\/jci.insight.147700","article-title":"Age-associated gut microbiota impair hippocampus-dependent memory in a vagus-dependent manner","volume":"7","author":"Rei","year":"2022","journal-title":"JCI Insight"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"113168","DOI":"10.1016\/j.isci.2025.113168","article-title":"Mozart\u2019s rhythm influence on Alzheimer\u2019s disease progression via modulation of pathological damage and cognition","volume":"28","author":"Li","year":"2025","journal-title":"iScience"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"80","DOI":"10.1186\/s12986-025-00977-2","article-title":"The effectiveness and safety of specific dietary supplements in modulating uric acid levels, oxidative stress, and lipid metabolism in patients: A network meta-analysis of 13 interventions","volume":"22","author":"Ye","year":"2025","journal-title":"Nutr. Metab."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1186\/s13024-025-00812-5","article-title":"Peripheral and central neuroimmune mechanisms in Alzheimer\u2019s disease pathogenesis","volume":"20","author":"Zhang","year":"2025","journal-title":"Mol. Neurodegener."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12974-022-02510-1","article-title":"The function of gut microbiota in immune-related neurological disorders: A review","volume":"19","author":"Sittipo","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"332","DOI":"10.1186\/s13287-019-1432-5","article-title":"Extracellular vesicles derived from human Wharton\u2019s jelly mesenchymal stem cells protect hippocampal neurons from oxidative stress and synapse damage induced by amyloid-\u03b2 oligomers","volume":"10","author":"Batista","year":"2019","journal-title":"Stem Cell Res. Ther."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1186\/s12974-020-01916-z","article-title":"Ingestion of Lactobacillus intestinalis and Lactobacillus reuteri causes depression- and anhedonia-like phenotypes in antibiotic-treated mice via the vagus nerve","volume":"17","author":"Wang","year":"2020","journal-title":"J. Neuroinflamm."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s12974-022-02396-z","article-title":"Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats","volume":"19","author":"Namgung","year":"2022","journal-title":"J. Neuroinflamm."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.5740\/jaoacint.19-0133","article-title":"Natural Polyphenols: Chemical Classification, Definition of Classes, Subcategories, and Structures","volume":"102","author":"Singla","year":"2019","journal-title":"J. AOAC Int."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Akhtar, N., Siddiqui, A.J., Ramzan, M., Uddin, J., Asmari, M., El-Seedi, H.R., and Musharraf, S.G. (2024). Investigation of Pharmacologically Important Polyphenolic Secondary Metabolites in Plant-based Food Samples Using HPLC-DAD. Plants, 13.","DOI":"10.3390\/plants13101311"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"Wu, Y., Liu, Y., Jia, Y., Zhang, H., and Ren, F. (2024). Formation and Application of Starch-Polyphenol Complexes: Influencing Factors and Rapid Screening Based on Chemometrics. Foods, 13.","DOI":"10.3390\/foods13101557"},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Calderaro, A., Patan\u00e8, G.T., Tellone, E., Barreca, D., Ficarra, S., Misiti, F., and Lagan\u00e0, G. (2022). The Neuroprotective Potentiality of Flavonoids on Alzheimer\u2019s Disease. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314835"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"7710","DOI":"10.1073\/pnas.0910723107","article-title":"EGCG remodels mature alpha-synuclein and amyloid-beta fibrils and reduces cellular toxicity","volume":"107","author":"Bieschke","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1038\/nsmb.1437","article-title":"EGCG redirects amyloidogenic polypeptides into unstructured, off-pathway oligomers","volume":"15","author":"Ehrnhoefer","year":"2008","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4712","DOI":"10.1007\/s12035-023-03867-x","article-title":"Complicated Role of Post-translational Modification and Protease-Cleaved Fragments of Tau in Alzheimer\u2019s Disease and Other Tauopathies","volume":"61","author":"Yang","year":"2024","journal-title":"Mol. Neurobiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1586\/14789450.5.2.207","article-title":"Biochemistry of Tau in Alzheimer\u2019s disease and related neurological disorders","volume":"5","author":"Sergeant","year":"2008","journal-title":"Expert Rev. Proteom."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"22959","DOI":"10.1038\/s41598-021-02248-5","article-title":"Mechanism of quercetin therapeutic targets for Alzheimer disease and type 2 diabetes mellitus","volume":"11","author":"Zu","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Jiang, W., Luo, T., Li, S., Zhou, Y., Shen, X.Y., He, F., Xu, J., and Wang, H.Q. (2016). Quercetin Protects against Okadaic Acid-Induced Injury via MAPK and PI3K\/Akt\/GSK3\u03b2 Signaling Pathways in HT22 Hippocampal Neurons. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0152371"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Bao, D., Wang, J., Pang, X., and Liu, H. (2017). Protective Effect of Quercetin against Oxidative Stress-Induced Cytotoxicity in Rat Pheochromocytoma (PC-12) Cells. Molecules, 22.","DOI":"10.3390\/molecules22071122"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1007\/s10571-017-0519-8","article-title":"Protective Role of Naringenin Against A\u03b2(25-35)-Caused Damage via ER and PI3K\/Akt-Mediated Pathways","volume":"38","author":"Zhang","year":"2018","journal-title":"Cell. Mol. Neurobiol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"12579","DOI":"10.1038\/s41598-020-69429-6","article-title":"EGCG impedes human Tau aggregation and interacts with Tau","volume":"10","author":"Sonawane","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.redox.2018.01.008","article-title":"13 reasons why the brain is susceptible to oxidative stress","volume":"15","author":"Cobley","year":"2018","journal-title":"Redox Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"116359","DOI":"10.1016\/j.ejmech.2024.116359","article-title":"Natural polyphenol: Their pathogenesis-targeting therapeutic potential in Alzheimer\u2019s disease","volume":"269","author":"Niu","year":"2024","journal-title":"Eur. J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1016\/0891-5849(94)90202-X","article-title":"The correlation between active oxygens scavenging and antioxidative effects of flavonoids","volume":"16","author":"Hanasaki","year":"1994","journal-title":"Free Radic. Biol. Med."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Kim, M.J., Hwang, E.S., Kim, K.J., Maeng, S., Heo, H.J., Park, J.H., and Kim, D.O. (2021). Anti-Amnesic Effects of Epigallocatechin Gallate on Scopolamine-Induced Learning and Memory Dysfunction in Sprague-Dawley Rats. Antioxidants, 11.","DOI":"10.3390\/antiox11010001"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Li, J., Sun, M., Cui, X., and Li, C. (2022). Protective Effects of Flavonoids against Alzheimer\u2019s Disease: Pathological Hypothesis, Potential Targets, and Structure-Activity Relationship. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231710020"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s12958-024-01265-z","article-title":"Quercetin enhances decidualization through AKT-ERK-p53 signaling and supports a role for senescence in endometriosis","volume":"22","author":"Delenko","year":"2024","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1038\/s41420-023-01730-5","article-title":"Emerging role and therapeutic implications of p53 in intervertebral disc degeneration","volume":"9","author":"Wang","year":"2023","journal-title":"Cell Death Discov."},{"key":"ref_69","first-page":"9834742","article-title":"PI3K\/Akt and ERK1\/2 Signalling Are Involved in Quercetin-Mediated Neuroprotection against Copper-Induced Injury","volume":"2020","author":"Hof","year":"2020","journal-title":"Oxidative Med. Cell. Longev."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"e70322","DOI":"10.1002\/vms3.70322","article-title":"Therapeutic Effects of Naringin on Bisphenol A-Induced Oxidative Stress Damage in Nervous and Reproductive Systems of Cockerel Chickens","volume":"11","author":"Esuola","year":"2025","journal-title":"Vet. Med. Sci."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1007\/s40495-021-00269-2","article-title":"Myricetin: A Multifunctional Flavonol in Biomedicine","volume":"8","author":"Agraharam","year":"2022","journal-title":"Curr. Pharmacol. Rep."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.tox.2011.03.001","article-title":"Advances in metal-induced oxidative stress and human disease","volume":"283","author":"Jomova","year":"2011","journal-title":"Toxicology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1139\/apnm-2013-0262","article-title":"Neuroprotective efficacy of a combination of fish oil and ferulic acid against 3-nitropropionic acid-induced oxidative stress and neurotoxicity in rats: Behavioural and biochemical evidence","volume":"39","author":"Muralidhara","year":"2014","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Varesi, A., Campagnoli, L.I.M., Carrara, A., Pola, I., Floris, E., Ricevuti, G., Chirumbolo, S., and Pascale, A. (2023). Non-Enzymatic Antioxidants against Alzheimer\u2019s Disease: Prevention, Diagnosis and Therapy. Antioxidants, 12.","DOI":"10.3390\/antiox12010180"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"3723567","DOI":"10.1155\/2022\/3723567","article-title":"Ferulic Acid Exerts Neuroprotective Effects via Autophagy Induction in C. elegans and Cellular Models of Parkinson\u2019s Disease","volume":"2022","author":"Long","year":"2022","journal-title":"Oxid. Med. Cell Longev."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"432","DOI":"10.2174\/1570159X19666210421092725","article-title":"Do Naturally Occurring Antioxidants Protect Against Neurodegeneration of the Dopaminergic System? A Systematic Revision in Animal Models of Parkinson\u2019s Disease","volume":"20","author":"Costas","year":"2022","journal-title":"Curr. Neuropharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Meraz-R\u00edos, M.A., Toral-Rios, D., Franco-Bocanegra, D., Villeda-Hern\u00e1ndez, J., and Campos-Pe\u00f1a, V. (2013). Inflammatory process in Alzheimer\u2019s Disease. Front. Integr. Neurosci., 7.","DOI":"10.3389\/fnint.2013.00059"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1992","DOI":"10.2174\/1570159X21666221216162606","article-title":"Metabolic Reprogramming of Microglia in Sepsis-Associated Encephalopathy: Insights from Neuroinflammation","volume":"21","author":"Gao","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Alami, M., Boumezough, K., Zerif, E., Zoubdane, N., Khalil, A., Bunt, T., Laurent, B., Witkowski, J.M., Ramassamy, C., and Boulbaroud, S. (2024). In Vitro Assessment of the Neuroprotective Effects of Pomegranate (Punica granatum L.) Polyphenols Against Tau Phosphorylation, Neuroinflammation, and Oxidative Stress. Nutrients, 16.","DOI":"10.3390\/nu16213667"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2374608","DOI":"10.1080\/19490976.2024.2374608","article-title":"Quinic acid alleviates high-fat diet-induced neuroinflammation by inhibiting DR3\/IKK\/NF-\u03baB signaling via gut microbial tryptophan metabolites","volume":"16","author":"Li","year":"2024","journal-title":"Gut Microbes"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"111017","DOI":"10.1016\/j.biopha.2020.111017","article-title":"Myricetin: A review of the most recent research","volume":"134","author":"Song","year":"2021","journal-title":"Biomed. Pharmacother."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1112","DOI":"10.2174\/1389201024666230801095526","article-title":"Pre-clinical Evidence-based Neuroprotective Potential of Naringin against Alzheimer\u2019s Disease-like Pathology: A Comprehensive Review","volume":"25","author":"Singh","year":"2024","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"154890","DOI":"10.1016\/j.phymed.2023.154890","article-title":"Molecular mechanisms and therapeutic potential of icariin in the treatment of Alzheimer\u2019s disease","volume":"116","author":"Zheng","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"e16994","DOI":"10.1016\/j.heliyon.2023.e16994","article-title":"The effect of grape seed procyanidins extract on cognitive function in elderly people with mild cognitive impairment: A randomized, double-blind, placebo-controlled clinical trial","volume":"9","author":"Li","year":"2023","journal-title":"Heliyon"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.1016\/j.jalz.2019.04.008","article-title":"Blood amyloid levels and risk of dementia in the Ginkgo Evaluation of Memory Study (GEMS): A longitudinal analysis","volume":"15","author":"Lopez","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Choi, W.Y., Lee, W.K., Kim, T.H., Ryu, Y.K., Park, A., Lee, Y.J., Heo, S.J., Oh, C., Chung, Y.C., and Kang, D.H. (2022). The Effects of Spirulina maxima Extract on Memory Improvement in Those with Mild Cognitive Impairment: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial. Nutrients, 14.","DOI":"10.3390\/nu14183714"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1212\/WNL.0000000000002035","article-title":"A randomized, double-blind, placebo-controlled trial of resveratrol for Alzheimer disease","volume":"85","author":"Turner","year":"2015","journal-title":"Neurology"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"e2216932120","DOI":"10.1073\/pnas.2216932120","article-title":"Dietary flavanols restore hippocampal-dependent memory in older adults with lower diet quality and lower habitual flavanol consumption","volume":"120","author":"Brickman","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12974-016-0779-0","article-title":"Resveratrol regulates neuro-inflammation and induces adaptive immunity in Alzheimer\u2019s disease","volume":"14","author":"Moussa","year":"2017","journal-title":"J. Neuroinflamm."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1055\/s-0031-1291217","article-title":"Efficacy and tolerability of a once daily formulation of Ginkgo biloba extract EGb 761\u00ae in Alzheimer\u2019s disease and vascular dementia: Results from a randomised controlled trial","volume":"45","author":"Ihl","year":"2012","journal-title":"Pharmacopsychiatry"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Lippolis, T., Cofano, M., Caponio, G.R., De Nunzio, V., and Notarnicola, M. (2023). Bioaccessibility and Bioavailability of Diet Polyphenols and Their Modulation of Gut Microbiota. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24043813"},{"key":"ref_92","doi-asserted-by":"crossref","unstructured":"Chiang, M.H., Ho, S.M., Wu, H.Y., Lin, Y.C., Tsai, W.H., Wu, T., Lai, C.H., and Wu, C.L. (2022). Drosophila Model for Studying Gut Microbiota in Behaviors and Neurodegenerative Diseases. Biomedicines, 10.","DOI":"10.3390\/biomedicines10030596"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1002\/mnfr.201400544","article-title":"Role of intestinal microbiota in the generation of polyphenol-derived phenolic acid mediated attenuation of Alzheimer\u2019s disease \u03b2-amyloid oligomerization","volume":"59","author":"Wang","year":"2015","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1073\/pnas.1016217108","article-title":"Discovery of the curcumin metabolic pathway involving a unique enzyme in an intestinal microorganism","volume":"108","author":"Hassaninasab","year":"2011","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1039\/C3FO60370A","article-title":"Chemopreventative effects of tetrahydrocurcumin on human diseases","volume":"5","author":"Wu","year":"2014","journal-title":"Food Funct."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"112459","DOI":"10.1016\/j.exger.2024.112459","article-title":"The identification of active compounds and therapeutic properties of fermented and non-fermented red sorghum for the treatment of Alzheimer\u2019s dementia","volume":"192","author":"Akbari","year":"2024","journal-title":"Exp. Gerontol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"3507","DOI":"10.1007\/s00253-020-10461-x","article-title":"Bidirectional interactions between curcumin and gut microbiota in transgenic mice with Alzheimer\u2019s disease","volume":"104","author":"Sun","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.1016\/j.numecd.2013.01.002","article-title":"Anti-estrogenic activity of a human resveratrol metabolite","volume":"23","author":"Ruotolo","year":"2013","journal-title":"Nutr. Metab. Cardiovasc. Dis."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"3305","DOI":"10.1021\/acs.jafc.7b00943","article-title":"Curcuminoid Demethylation as an Alternative Metabolism by Human Intestinal Microbiota","volume":"65","author":"Burapan","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"236","DOI":"10.3390\/ph5020236","article-title":"Probiotic Ferulic Acid Esterase Active Lactobacillus fermentum NCIMB 5221 APA Microcapsules for Oral Delivery: Preparation and In Vitro Characterization","volume":"5","author":"Saha","year":"2012","journal-title":"Pharmaceuticals"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"310","DOI":"10.1089\/jmf.2008.0166","article-title":"Orally delivered microencapsulated live probiotic formulation lowers serum lipids in hypercholesterolemic hamsters","volume":"12","author":"Bhathena","year":"2009","journal-title":"J. Med. Food"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/j.fct.2013.12.024","article-title":"Ferulic acid: Pharmacological and toxicological aspects","volume":"65","author":"Mancuso","year":"2014","journal-title":"Food Chem. Toxicol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"4046","DOI":"10.1039\/C9FO00213H","article-title":"A holistic view of gallic acid-induced attenuation in colitis based on microbiome-metabolomics analysis","volume":"10","author":"Li","year":"2019","journal-title":"Food Funct."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"2175","DOI":"10.1080\/10408398.2020.1773390","article-title":"Potential implications of polyphenols on aging considering oxidative stress, inflammation, autophagy, and gut microbiota","volume":"61","author":"Wu","year":"2021","journal-title":"Crit. Rev. Food Sci. Nutr."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1002\/biof.1081","article-title":"Flavonols enhanced production of anti-inflammatory substance(s) by Bifidobacterium adolescentis: Prebiotic actions of galangin, quercetin, and fisetin","volume":"39","author":"Kawabata","year":"2013","journal-title":"Biofactors"},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"118627","DOI":"10.1016\/j.lfs.2020.118627","article-title":"Role of gut-brain axis, gut microbial composition, and probiotic intervention in Alzheimer\u2019s disease","volume":"264","author":"Kesika","year":"2021","journal-title":"Life Sci."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.anaerobe.2014.03.003","article-title":"Lactobacillus pentosus var. plantarum C29 ameliorates memory impairment and inflammaging in a D-galactose-induced accelerated aging mouse model","volume":"27","author":"Woo","year":"2014","journal-title":"Anaerobe"},{"key":"ref_108","doi-asserted-by":"crossref","unstructured":"Akbari, E., Asemi, Z., Daneshvar Kakhaki, R., Bahmani, F., Kouchaki, E., Tamtaji, O.R., Hamidi, G.A., and Salami, M. (2016). Effect of Probiotic Supplementation on Cognitive Function and Metabolic Status in Alzheimer\u2019s Disease: A Randomized, Double-Blind and Controlled Trial. Front. Aging Neurosci., 8.","DOI":"10.3389\/fnagi.2016.00256"},{"key":"ref_109","first-page":"Kc01","article-title":"Anti-Alzheimer Properties of Probiotic, Lactobacillus plantarum MTCC 1325 in Alzheimer\u2019s Disease induced Albino Rats","volume":"11","author":"Nimgampalle","year":"2017","journal-title":"J. Clin. Diagn. Res."},{"key":"ref_110","doi-asserted-by":"crossref","unstructured":"Scazzocchio, B., Minghetti, L., and D\u2019Archivio, M. (2020). Interaction between Gut Microbiota and Curcumin: A New Key of Understanding for the Health Effects of Curcumin. Nutrients, 12.","DOI":"10.3390\/nu12092499"},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Zhang, Z., Peng, X., Li, S., Zhang, N., Wang, Y., and Wei, H. (2014). Isolation and identification of quercetin degrading bacteria from human fecal microbes. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090531"},{"key":"ref_112","doi-asserted-by":"crossref","unstructured":"Bayazid, A.B., and Lim, B.O. (2024). Therapeutic Effects of Plant Anthocyanin against Alzheimer\u2019s Disease and Modulate Gut Health, Short-Chain Fatty Acids. Nutrients, 16.","DOI":"10.20944\/preprints202404.1532.v1"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s41387-024-00268-4","article-title":"Myricetin alleviates diabetic cardiomyopathy by regulating gut microbiota and their metabolites","volume":"14","author":"Zhu","year":"2024","journal-title":"Nutr. Diabetes"},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"120714","DOI":"10.1016\/j.carbpol.2023.120714","article-title":"Brain targeted peptide-functionalized chitosan nanoparticles for resveratrol delivery: Impact on insulin resistance and gut microbiota in obesity-related Alzheimer\u2019s disease","volume":"310","author":"Yang","year":"2023","journal-title":"Carbohydr. Polym."},{"key":"ref_115","doi-asserted-by":"crossref","unstructured":"Qu, Y., Wu, Y., Cheng, W., Wang, D., Zeng, L., Wang, Y., Li, T., Zhang, L., Yang, J., and Sun, L. (2022). Amelioration of cognitive impairment using epigallocatechin-3-gallate in ovariectomized mice fed a high-fat diet involves remodeling with Prevotella and Bifidobacteriales. Front. Pharmacol., 13.","DOI":"10.3389\/fphar.2022.1079313"},{"key":"ref_116","doi-asserted-by":"crossref","unstructured":"Qu, Y., Li, X., Xu, F., Zhao, S., Wu, X., Wang, Y., and Xie, J. (2021). Kaempferol Alleviates Murine Experimental Colitis by Restoring Gut Microbiota and Inhibiting the LPS-TLR4-NF-\u03baB Axis. Front. Immunol., 12.","DOI":"10.3389\/fimmu.2021.679897"},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1038\/s41575-022-00631-9","article-title":"Akkermansia muciniphila: Paradigm for next-generation beneficial microorganisms","volume":"19","author":"Cani","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1186\/s40168-021-01115-9","article-title":"Gut microbiota from green tea polyphenol-dosed mice improves intestinal epithelial homeostasis and ameliorates experimental colitis","volume":"9","author":"Wu","year":"2021","journal-title":"Microbiome"},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.neurobiolaging.2016.08.019","article-title":"Association of brain amyloidosis with pro-inflammatory gut bacterial taxa and peripheral inflammation markers in cognitively impaired elderly","volume":"49","author":"Cattaneo","year":"2017","journal-title":"Neurobiol. Aging"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"1361780","DOI":"10.1080\/16546628.2017.1361780","article-title":"Regulative effects of curcumin spice administration on gut microbiota and its pharmacological implications","volume":"61","author":"Shen","year":"2017","journal-title":"Food Nutr. Res."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1097\/MIB.0000000000000522","article-title":"The Role of Curcumin in Modulating Colonic Microbiota During Colitis and Colon Cancer Prevention","volume":"21","author":"McFadden","year":"2015","journal-title":"Inflamm. Bowel Dis."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"541","DOI":"10.1038\/nature12506","article-title":"Richness of human gut microbiome correlates with metabolic markers","volume":"500","author":"Nielsen","year":"2013","journal-title":"Nature"},{"key":"ref_123","doi-asserted-by":"crossref","unstructured":"Zhu, Y., Li, Y., Zhang, Q., Song, Y., Wang, L., and Zhu, Z. (2022). Interactions Between Intestinal Microbiota and Neural Mitochondria: A New Perspective on Communicating Pathway From Gut to Brain. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.798917"},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"46406","DOI":"10.1021\/acsami.1c14818","article-title":"Oral Administration of Resveratrol-Selenium-Peptide Nanocomposites Alleviates Alzheimer\u2019s Disease-like Pathogenesis by Inhibiting A\u03b2 Aggregation and Regulating Gut Microbiota","volume":"13","author":"Li","year":"2021","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"1675","DOI":"10.1007\/s12035-024-04343-w","article-title":"The Role of Gut Microbiota in the Neuroprotective Effects of Selenium in Alzheimer\u2019s Disease","volume":"62","author":"Skalny","year":"2025","journal-title":"Mol. Neurobiol."},{"key":"ref_126","doi-asserted-by":"crossref","unstructured":"Makarewicz, M., Dro\u017cd\u017c, I., Tarko, T., and Duda-Chodak, A. (2021). The Interactions between Polyphenols and Microorganisms, Especially Gut Microbiota. Antioxidants, 10.","DOI":"10.3390\/antiox10020188"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"154979","DOI":"10.1016\/j.phymed.2023.154979","article-title":"Interactions between gut microbiota and polyphenols: A mechanistic and metabolomic review","volume":"119","author":"Cheng","year":"2023","journal-title":"Phytomedicine"},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"1243","DOI":"10.1038\/nsmb.2676","article-title":"Divergent evolution of protein conformational dynamics in dihydrofolate reductase","volume":"20","author":"Bhabha","year":"2013","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"1669","DOI":"10.1074\/jbc.M406848200","article-title":"Determination of selectivity and efficacy of fatty acid synthesis inhibitors","volume":"280","author":"Kodali","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"veac097","DOI":"10.1093\/ve\/veac097","article-title":"Viral origin of eukaryotic type IIA DNA topoisomerases","volume":"8","author":"Guglielmini","year":"2022","journal-title":"Virus Evol."},{"key":"ref_131","doi-asserted-by":"crossref","unstructured":"Duda-Chodak, A., Tarko, T., and Petka-Poniatowska, K. (2023). Antimicrobial Compounds in Food Packaging. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24032457"},{"key":"ref_132","doi-asserted-by":"crossref","unstructured":"Peng, F., Chen, L., Wang, X., Yu, Z., Cheng, C., and Yang, Y. (2023). Effect of Chestnut (Castanea mollissima Blume) Bur Polyphenol Extract on Shigella dysenteriae: Antibacterial Activity and the Mechanism. Molecules, 28.","DOI":"10.3390\/molecules28196990"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"106763","DOI":"10.1016\/j.fitote.2025.106763","article-title":"Plant polyphenols: Antibacterial activity and structural insights","volume":"185","author":"Li","year":"2025","journal-title":"Fitoterapia"},{"key":"ref_134","doi-asserted-by":"crossref","unstructured":"Fratianni, F., Cozzolino, A., De Feo, V., Coppola, R., Ombra, M.N., and Nazzaro, F. (2019). Polyphenols, Antioxidant, Antibacterial, and Biofilm Inhibitory Activities of Peel and Pulp of Citrus medica L., Citrus bergamia, and Citrus medica cv. Sal\u00f2 Cultivated in Southern Italy. Molecules, 24.","DOI":"10.3390\/molecules24244577"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1016\/j.copbio.2011.08.007","article-title":"Polyphenols as antimicrobial agents","volume":"23","author":"Daglia","year":"2012","journal-title":"Curr. Opin. Biotechnol."},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1002\/ptr.5616","article-title":"Scope of Hydrolysable Tannins as Possible Antimicrobial Agent","volume":"30","author":"Ekambaram","year":"2016","journal-title":"Phytother. Res."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"1139","DOI":"10.1002\/cbdv.201000264","article-title":"Evaluation of the antimicrobial potential of two flavonoids isolated from limnophila plants","volume":"8","author":"Brahmachari","year":"2011","journal-title":"Chem. Biodivers."},{"key":"ref_138","doi-asserted-by":"crossref","unstructured":"Xie, Y., Chen, J., Xiao, A., and Liu, L. (2017). Antibacterial Activity of Polyphenols: Structure-Activity Relationship and Influence of Hyperglycemic Condition. Molecules, 22.","DOI":"10.3390\/molecules22111913"},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"94","DOI":"10.4014\/jmb.2304.04019","article-title":"Polyphenol Contents, Gas Chromatography-Mass Spectrometry (GC-MS) and Antibacterial Activity of Methanol Extract and Fractions of Sonneratia Caseolaris Fruits from Ben Tre Province in Vietnam","volume":"34","author":"Tran","year":"2024","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_140","doi-asserted-by":"crossref","first-page":"15064","DOI":"10.1021\/acs.jafc.3c03183","article-title":"Red Cabbage Anthocyanins Attenuate Cognitive Impairment By Attenuating Neuroinflammation and Regulating Gut Microbiota in Aging Mice","volume":"71","author":"Zhang","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Lamichhane, G., Liu, J., Lee, S.J., Lee, D.Y., Zhang, G., and Kim, Y. (2024). Curcumin Mitigates the High-Fat High-Sugar Diet-Induced Impairment of Spatial Memory, Hepatic Metabolism, and the Alteration of the Gut Microbiome in Alzheimer\u2019s Disease-Induced (3xTg-AD) Mice. Nutrients, 16.","DOI":"10.3390\/nu16020240"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"124316","DOI":"10.1016\/j.ijbiomac.2023.124316","article-title":"Resveratrol-loaded selenium\/chitosan nano-flowers alleviate glucolipid metabolism disorder-associated cognitive impairment in Alzheimer\u2019s disease","volume":"239","author":"Yang","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"125129","DOI":"10.1016\/j.ijpharm.2024.125129","article-title":"Cellulose-like chitosan microfibrils facilitate targeted release and enhance the prolonged residence time of quercetin-selenium nanoparticles for Alzheimer\u2019s disease treatment","volume":"670","author":"Fang","year":"2025","journal-title":"Int. J. Pharm."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"e1901019","DOI":"10.1002\/mnfr.201901019","article-title":"DietaryAdvancedGlycationEnd Products-InducedCognitive Impairment in Aged ICR Mice: Protective Role of Quercetin","volume":"64","author":"Yang","year":"2020","journal-title":"Mol. Nutr. Food Res."},{"key":"ref_145","doi-asserted-by":"crossref","unstructured":"Shi, J., Chen, J., Xie, X., Li, Y., Ye, W., Yao, J., Zhang, X., Zhang, T., and Gao, J. (2023). Baicalein-corrected gut microbiota may underlie the amelioration of memory and cognitive deficits in APP\/PS1 mice. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.1132857"},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"118598","DOI":"10.1016\/j.biopha.2025.118598","article-title":"Neuroinflammatory suppression with protocatechuic acid attenuates Alzheimer\u2019s disease phenotypes in 5 \u00d7FAD transgenic mice","volume":"192","author":"Kim","year":"2025","journal-title":"Biomed. Pharmacother."},{"key":"ref_147","doi-asserted-by":"crossref","unstructured":"Chen, Y., and Tang, S. (2023). Gut microbiota and immune mediation: A Mendelian randomization study on granulomatosis with polyangiitis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1296016"},{"key":"ref_148","doi-asserted-by":"crossref","first-page":"240","DOI":"10.17305\/bb.2025.12921","article-title":"Gut microbial metabolites and the brain-gut axis in Alzheimer\u2019s disease: A review","volume":"26","author":"Ji","year":"2025","journal-title":"Biomol. Biomed."},{"key":"ref_149","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1007\/s13668-025-00619-2","article-title":"Gut Microbiome, Diet and Depression: Literature Review of Microbiological, Nutritional and Neuroscientific Aspects","volume":"14","author":"Clerici","year":"2025","journal-title":"Curr. Nutr. Rep."},{"key":"ref_150","doi-asserted-by":"crossref","unstructured":"Muraleedharan, A., and Ray, S.K. (2024). Epigallocatechin-3-Gallate and Genistein for Decreasing Gut Dysbiosis, Inhibiting Inflammasomes, and Aiding Autophagy in Alzheimer\u2019s Disease. Brain Sci., 14.","DOI":"10.3390\/brainsci14010096"},{"key":"ref_151","doi-asserted-by":"crossref","unstructured":"Alrafas, H.R., Busbee, P.B., Chitrala, K.N., Nagarkatti, M., and Nagarkatti, P. (2020). Alterations in the Gut Microbiome and Suppression of Histone Deacetylases by Resveratrol Are Associated with Attenuation of Colonic Inflammation and Protection Against Colorectal Cancer. J. Clin. Med., 9.","DOI":"10.3390\/jcm9061796"},{"key":"ref_152","doi-asserted-by":"crossref","first-page":"109641","DOI":"10.1016\/j.celrep.2021.109641","article-title":"Myricetin supplementation decreases hepatic lipid synthesis and inflammation by modulating gut microbiota","volume":"36","author":"Sun","year":"2021","journal-title":"Cell Rep."},{"key":"ref_153","doi-asserted-by":"crossref","first-page":"19376","DOI":"10.1073\/pnas.2000047117","article-title":"Microbial tryptophan metabolites regulate gut barrier function via the aryl hydrocarbon receptor","volume":"117","author":"Scott","year":"2020","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_154","doi-asserted-by":"crossref","unstructured":"Qin, N., Xie, X., Deng, R., Gao, S., and Zhu, T. (2025). The role of the tryptophan metabolites in gut microbiota-brain axis and potential treatments: A focus on ischemic stroke. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1578018"},{"key":"ref_155","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1186\/s40168-023-01656-1","article-title":"Microbiota-indole 3-propionic acid-brain axis mediates abnormal synaptic pruning of hippocampal microglia and susceptibility to ASD in IUGR offspring","volume":"11","author":"Wang","year":"2023","journal-title":"Microbiome"},{"key":"ref_156","doi-asserted-by":"crossref","unstructured":"Kyriazi, A.A., Karaglani, M., Agelaki, S., and Baritaki, S. (2024). Intratumoral Microbiome: Foe or Friend in Reshaping the Tumor Microenvironment Landscape?. Cells, 13.","DOI":"10.20944\/preprints202406.0399.v1"},{"key":"ref_157","doi-asserted-by":"crossref","first-page":"1981","DOI":"10.1111\/cns.14154","article-title":"Activation of the bile acid receptors TGR5 and FXR in the spinal dorsal horn alleviates neuropathic pain","volume":"29","author":"Wu","year":"2023","journal-title":"CNS Neurosci. Ther."},{"key":"ref_158","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.freeradbiomed.2019.09.002","article-title":"Activation of TGR5 with INT-777 attenuates oxidative stress and neuronal apoptosis via cAMP\/PKC\u03b5\/ALDH2 pathway after subarachnoid hemorrhage in rats","volume":"143","author":"Zuo","year":"2019","journal-title":"Free Radic. Biol. Med."},{"key":"ref_159","doi-asserted-by":"crossref","unstructured":"Wu, X., Yin, S., Cheng, C., Xu, C., and Peng, J. (2021). Inclusion of Soluble Fiber During Gestation Regulates Gut Microbiota, Improves Bile Acid Homeostasis, and Enhances the Reproductive Performance of Sows. Front. Vet. Sci., 8.","DOI":"10.3389\/fvets.2021.756910"},{"key":"ref_160","first-page":"e25537","article-title":"A Systematic Review of the Efficacy and Safety of Fecal Microbiota Transplantation in the Treatment of Hepatic Encephalopathy and Clostridioides difficile Infection in Patients with Cirrhosis","volume":"14","author":"Tun","year":"2022","journal-title":"Cureus"},{"key":"ref_161","doi-asserted-by":"crossref","first-page":"1619","DOI":"10.3945\/jn.109.104638","article-title":"Butyrate enhances the intestinal barrier by facilitating tight junction assembly via activation of AMP-activated protein kinase in Caco-2 cell monolayers","volume":"139","author":"Peng","year":"2009","journal-title":"J. Nutr."},{"key":"ref_162","doi-asserted-by":"crossref","unstructured":"Naschberger, E., Flierl, C., Huang, J., Erkert, L., Gamez-Belmonte, R., Gonzalez-Acera, M., Bober, M., Mehnert, M., Becker, C., and Schellerer, V.S. (2023). Analysis of the interferon-\u03b3-induced secretome of intestinal endothelial cells: Putative impact on epithelial barrier dysfunction in IBD. Front. Cell Dev. Biol., 11.","DOI":"10.3389\/fcell.2023.1213383"},{"key":"ref_163","doi-asserted-by":"crossref","first-page":"103751","DOI":"10.1016\/j.ebiom.2021.103751","article-title":"MUC2 and related bacterial factors: Therapeutic targets for ulcerative colitis","volume":"74","author":"Yao","year":"2021","journal-title":"EBioMedicine"},{"key":"ref_164","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1126\/science.aay7367","article-title":"Proximal colon-derived O-glycosylated mucus encapsulates and modulates the microbiota","volume":"370","author":"Bergstrom","year":"2020","journal-title":"Science"},{"key":"ref_165","doi-asserted-by":"crossref","first-page":"113","DOI":"10.3892\/ijmm.2023.5316","article-title":"Intestinal changes in permeability, tight junction and mucin synthesis in a mouse model of Alzheimer\u2019s disease","volume":"52","author":"He","year":"2023","journal-title":"Int. J. Mol. Med."},{"key":"ref_166","doi-asserted-by":"crossref","first-page":"1337","DOI":"10.3233\/JAD-180176","article-title":"Gut Microbiota is Altered in Patients with Alzheimer\u2019s Disease","volume":"63","author":"Zhuang","year":"2018","journal-title":"J. Alzheimers Dis."},{"key":"ref_167","doi-asserted-by":"crossref","first-page":"4325","DOI":"10.3382\/ps\/pex266","article-title":"Resveratrol alleviates heat stress-induced impairment of intestinal morphology, microflora, and barrier integrity in broilers","volume":"96","author":"Zhang","year":"2017","journal-title":"Poult. Sci."},{"key":"ref_168","doi-asserted-by":"crossref","first-page":"544","DOI":"10.3934\/microbiol.2022035","article-title":"Impact of grape polyphenols on Akkermansia muciniphila and the gut barrier","volume":"8","author":"Mezhibovsky","year":"2022","journal-title":"AIMS Microbiol."},{"key":"ref_169","doi-asserted-by":"crossref","first-page":"2168","DOI":"10.1002\/fsn3.2828","article-title":"Effects of dietary protein level on small intestinal morphology, occludin protein, and bacterial diversity in weaned piglets","volume":"10","author":"Ren","year":"2022","journal-title":"Food Sci. Nutr."},{"key":"ref_170","doi-asserted-by":"crossref","first-page":"101269","DOI":"10.1016\/j.redox.2019.101269","article-title":"Anthocyanins protect the gastrointestinal tract from high fat diet-induced alterations in redox signaling, barrier integrity and dysbiosis","volume":"26","author":"Cremonini","year":"2019","journal-title":"Redox Biol."},{"key":"ref_171","doi-asserted-by":"crossref","first-page":"5449","DOI":"10.1007\/s00253-020-10527-w","article-title":"Protective effect of baicalin on the regulation of Treg\/Th17 balance, gut microbiota and short-chain fatty acids in rats with ulcerative colitis","volume":"104","author":"Zhu","year":"2020","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_172","doi-asserted-by":"crossref","first-page":"129532","DOI":"10.1016\/j.foodchem.2021.129532","article-title":"Intestinal pharmacokinetics of resveratrol and regulatory effects of resveratrol metabolites on gut barrier and gut microbiota","volume":"357","author":"Zhang","year":"2021","journal-title":"Food Chem."},{"key":"ref_173","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1007\/s13105-024-01046-7","article-title":"Polyphenols and metabolism: From present knowledge to future challenges","volume":"80","author":"Eseberri","year":"2024","journal-title":"J. Physiol. Biochem."},{"key":"ref_174","doi-asserted-by":"crossref","unstructured":"Yang, S., Yan, C., Cai, J., Pan, Y., and Han, Q. (2024). Research Progress in Nanoparticle Inhibitors for Crude Oil Asphaltene Deposition. Molecules, 29.","DOI":"10.3390\/molecules29051135"},{"key":"ref_175","doi-asserted-by":"crossref","first-page":"119110","DOI":"10.1016\/j.lfs.2021.119110","article-title":"Recent advances in breast cancer immunotherapy: The promising impact of nanomedicines","volume":"271","author":"Hashemzadeh","year":"2021","journal-title":"Life Sci."},{"key":"ref_176","doi-asserted-by":"crossref","first-page":"eabf9180","DOI":"10.1126\/sciadv.abf9180","article-title":"Targeting Alzheimer\u2019s disease with multimodal polypeptide-based nanoconjugates","volume":"7","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_177","doi-asserted-by":"crossref","first-page":"8837","DOI":"10.1021\/jf503199g","article-title":"Insight into curcumin-loaded \u03b2-lactoglobulin nanoparticles: Incorporation, particle disintegration, and releasing profiles","volume":"62","author":"Teng","year":"2014","journal-title":"J. Agric. Food Chem."},{"key":"ref_178","doi-asserted-by":"crossref","first-page":"111838","DOI":"10.1016\/j.colsurfb.2021.111838","article-title":"Systematically designed chitosan-coated solid lipid nanoparticles of ferulic acid for effective management of Alzheimer\u2019s disease: A preclinical evidence","volume":"205","author":"Saini","year":"2021","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_179","doi-asserted-by":"crossref","first-page":"2883","DOI":"10.1021\/acs.jafc.2c06809","article-title":"A Flower-like Brain Targeted Selenium Nanocluster Lowers the Chlorogenic Acid Dose for Ameliorating Cognitive Impairment in APP\/PS1 Mice","volume":"71","author":"Li","year":"2023","journal-title":"J. Agric. Food Chem."},{"key":"ref_180","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1007\/s00394-025-03614-z","article-title":"Refined highland barley ameliorates obesity-associated insulin resistance in high-fat diet-fed mice by targeting the gut microbiota and liver transcriptomics","volume":"64","author":"Wu","year":"2025","journal-title":"Eur. J. Nutr."},{"key":"ref_181","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1186\/s12974-021-02341-6","article-title":"Mechanisms underlying antidepressant effect of transcutaneous auricular vagus nerve stimulation on CUMS model rats based on hippocampal \u03b17nAchR\/NF-\u03baB signal pathway","volume":"18","author":"Wang","year":"2021","journal-title":"J. Neuroinflamm."},{"key":"ref_182","doi-asserted-by":"crossref","unstructured":"Jiang, S., Yu, C., Lv, B., He, S., Zheng, Y., Yang, W., Wang, B., Li, D., and Lin, J. (2023). Two-sample Mendelian randomization to study the causal association between gut microbiota and atherosclerosis. Front. Immunol., 14.","DOI":"10.3389\/fimmu.2023.1282072"},{"key":"ref_183","doi-asserted-by":"crossref","first-page":"113240","DOI":"10.1016\/j.celrep.2023.113240","article-title":"Toll-like receptor 4 and CD11b expressed on microglia coordinate eradication of Candida albicans cerebral mycosis","volume":"42","author":"Wu","year":"2023","journal-title":"Cell Rep."},{"key":"ref_184","doi-asserted-by":"crossref","unstructured":"Grgi\u0107, J., \u0160elo, G., Planini\u0107, M., Ti\u0161ma, M., and Buci\u0107-Koji\u0107, A. (2020). Role of the Encapsulation in Bioavailability of Phenolic Compounds. Antioxidants, 9.","DOI":"10.3390\/antiox9100923"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/604\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,9]],"date-time":"2026-01-09T05:23:21Z","timestamp":1767936201000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/2\/604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":184,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["ijms27020604"],"URL":"https:\/\/doi.org\/10.3390\/ijms27020604","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}