Overview of the potential involvement of human microbiomes in NDDs.
Microbiome
Potential involvement
Evidence
Main limitations
Gut
Modulation of neuroinflammation, oxidative stress, and neurotransmitter synthesis. ENS/vagus-mediated gut-brain communication. Immune, endocrine, and metabolite-mediated CNS effects. Influence on neurogenesis and protein aggregation.
High
High inter-individual and temporal variability. Reliance on animal models. Confounding factors (e.g., diet, drugs).
Oral
Circulation-mediated CNS effects via microbial metabolites. Oral pathogen-induced systemic inflammation. Modulation of CNS function via oral-gut interactions.
Medium
High inter-individual variability. Limited longitudinal human studies. Confounding factors (e.g., oral hygiene).
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References
Kovacs GG. Concepts and classification of neurodegenerative diseases.Handb Clin Neurol. 2017;145:301–7. [DOI] [PubMed]
Forrest SL, Kovacs GG. Current concepts and molecular pathology of neurodegenerative diseases.Pathology. 2025;57:178–90. [DOI] [PubMed]
American Psychiatric Association. Diagnostic and statistical manual of mental disorders: DSM-5-TR™. 5th ed. Washington: American Psychiatric Publishing Inc.; 2022.
Lanctôt KL, Amatniek J, Ancoli-Israel S, Arnold SE, Ballard C, Cohen-Mansfield J, et al. Neuropsychiatric signs and symptoms of Alzheimer’s disease: New treatment paradigms.Alzheimers Dement (N Y). 2017;3:440–9. [DOI] [PubMed] [PMC]
Cummings J, Ballard C, Tariot P, Owen R, Foff E, Youakim J, et al. Pimavanserin: Potential Treatment For Dementia-Related Psychosis.J Prev Alzheimers Dis. 2018;5:253–8. [DOI] [PubMed] [PMC]
Gupta R, Advani D, Yadav D, Ambasta RK, Kumar P. Dissecting the Relationship Between Neuropsychiatric and Neurodegenerative Disorders.Mol Neurobiol. 2023;60:6476–529. [DOI] [PubMed]
Borrego-Ruiz A, Borrego JJ. Microbioma intestinal humano, epigenética y enfermedades neurodegenerativas.enbio. 2024;16:19–23. [DOI]
Cavaliere F, Gülöksüz S. Shedding light on the etiology of neurodegenerative diseases and dementia: the exposome paradigm.Npj Ment Health Res. 2022;1:20. [DOI] [PubMed] [PMC]
Ogonowski NS, García-Marín LM, Fernando AS, Flores-Ocampo V, Rentería ME. Impact of genetic predisposition to late-onset neurodegenerative diseases on early life outcomes and brain structure.Transl Psychiatry. 2024;14:185. [DOI] [PubMed] [PMC]
Saeed A, Lopez O, Cohen A, Reis SE. Cardiovascular Disease and Alzheimer’s Disease: The Heart-Brain Axis.J Am Heart Assoc. 2023;12:e030780. [DOI] [PubMed] [PMC]
Islam S, Noorani A, Sun Y, Michikawa M, Zou K. Multi-functional role of apolipoprotein E in neurodegenerative diseases.Front Aging Neurosci. 2025;17:1535280. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. The role of the gut microbiome in Alzheimer’s disease pathophysiology.Curr Opin Neurol. 2025;38:157–62. [DOI] [PubMed]
Kapoor B, Biswas P, Gulati M, Rani P, Gupta R. Gut microbiome and Alzheimer’s disease: What we know and what remains to be explored.Ageing Res Rev. 2024;102:102570. [DOI] [PubMed]
Borrego-Ruiz A, Borrego JJ. Microbial Metabolomes in Alzheimer’s Disease: From Pathogenesis to Therapeutic Potential.Curr Issues Mol Biol. 2025;47:724. [DOI] [PubMed] [PMC]
Hou K, Wu Z, Chen X, Wang J, Zhang D, Xiao C, et al. Microbiota in health and diseases.Signal Transduct Target Ther. 2022;7:135. [DOI] [PubMed] [PMC]
Valles-Colomer M, Falony G, Darzi Y, Tigchelaar EF, Wang J, Tito RY, et al. The neuroactive potential of the human gut microbiota in quality of life and depression.Nat Microbiol. 2019;4:623–32. [DOI] [PubMed]
Cryan JF, O’Riordan KJ, Cowan CSM, Sandhu KV, Bastiaanssen TFS, Boehme M, et al. The Microbiota-Gut-Brain Axis.Physiol Rev. 2019;99:1877–2013. [DOI] [PubMed]
Gonçalves RA, De Felice FG. The crosstalk between brain and periphery: Implications for brain health and disease.Neuropharmacology. 2021;197:108728. [DOI] [PubMed]
Hashimoto K, Yang C. Special issue on “Brain-body communication in health and diseases”.Brain Res Bull. 2022;186:47–9. [DOI] [PubMed]
McEwen BS. Hormones and behavior and the integration of brain-body science.Horm Behav. 2020;119:104619. [DOI] [PubMed]
Integrative HMP (iHMP) Research Network Consortium. The Integrative Human Microbiome Project.Nature. 2019;569:641–8. [DOI] [PubMed] [PMC]
Yang S, Han SM, Lee J, Kim KS, Lee J, Lee D. Advancing Gut Microbiome Research: The Shift from Metagenomics to Multi-Omics and Future Perspectives.J Microbiol Biotechnol. 2025;35:e2412001. [DOI] [PubMed] [PMC]
Berg G, Rybakova D, Fischer D, Cernava T, Vergès MC, Charles T, et al. Microbiome definition re-visited: old concepts and new challenges.Microbiome. 2020;8:103. [DOI] [PubMed] [PMC]
Salvucci E. Microbiome, holobiont and the net of life.Crit Rev Microbiol. 2016;42:485–94. [DOI] [PubMed]
Hashimoto K. Emerging role of the host microbiome in neuropsychiatric disorders: overview and future directions.Mol Psychiatry. 2023;28:3625–37. [DOI] [PubMed] [PMC]
Petrillo F, Pignataro D, Lavano MA, Santella B, Folliero V, Zannella C, et al. Current Evidence on the Ocular Surface Microbiota and Related Diseases.Microorganisms. 2020;8:1033. [DOI] [PubMed] [PMC]
Reynoso-García J, Miranda-Santiago AE, Meléndez-Vázquez NM, Acosta-Pagán K, Sánchez-Rosado M, Díaz-Rivera J, et al. A complete guide to human microbiomes: Body niches, transmission, development, dysbiosis, and restoration.Front Syst Biol. 2022;2:951403. [DOI] [PubMed] [PMC]
Santoro A, Zhao J, Wu L, Carru C, Biagi E, Franceschi C. Microbiomes other than the gut: inflammaging and age-related diseases.Semin Immunopathol. 2020;42:589–605. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. An updated overview on the relationship between human gut microbiome dysbiosis and psychiatric and psychological disorders.Prog Neuropsychopharmacol Biol Psychiatry. 2024;128:110861. [DOI] [PubMed]
Chang L, Wei Y, Hashimoto K. Brain-gut-microbiota axis in depression: A historical overview and future directions.Brain Res Bull. 2022;182:44–56. [DOI] [PubMed]
Hashimoto K. Neuroinflammation through the vagus nerve-dependent gut-microbiota-brain axis in treatment-resistant depression.Prog Brain Res. 2023;278:61–77. [DOI] [PubMed]
Martínez JE, Vargas A, Pérez-Sánchez T, Encío IJ, Cabello-Olmo M, Barajas M. Human Microbiota Network: Unveiling Potential Crosstalk between the Different Microbiota Ecosystems and Their Role in Health and Disease.Nutrients. 2021;13:2905. [DOI] [PubMed] [PMC]
Baquero F, Nombela C. The microbiome as a human organ.Clin Microbiol Infect. 2012;18 Suppl 4:2–4. [DOI] [PubMed]
Gilbert SF, Sapp J, Tauber AI. A symbiotic view of life: we have never been individuals.Q Rev Biol. 2012;87:325–41. [DOI] [PubMed]
Foster KR, Schluter J, Coyte KZ, Rakoff-Nahoum S. The evolution of the host microbiome as an ecosystem on a leash.Nature. 2017;548:43–51. [DOI] [PubMed] [PMC]
Bordenstein SR, Theis KR. Host Biology in Light of the Microbiome: Ten Principles of Holobionts and Hologenomes.PLoS Biol. 2015;13:e1002226. [DOI] [PubMed] [PMC]
Thangaleela S, Sivamaruthi BS, Kesika P, Bharathi M, Chaiyasut C. Nasal Microbiota, Olfactory Health, Neurological Disorders and Aging-A Review.Microorganisms. 2022;10:1405. [DOI] [PubMed] [PMC]
Rinninella E, Raoul P, Cintoni M, Franceschi F, Miggiano GAD, Gasbarrini A, et al. What is the Healthy Gut Microbiota Composition? A Changing Ecosystem across Age, Environment, Diet, and Diseases.Microorganisms. 2019;7:14. [DOI] [PubMed] [PMC]
Sekirov I, Russell SL, Antunes LCM, Finlay BB. Gut microbiota in health and disease.Physiol Rev. 2010;90:859–904. [DOI] [PubMed]
Iizumi T, Battaglia T, Ruiz V, Perez GIP. Gut Microbiome and Antibiotics.Arch Med Res. 2017;48:727–34. [DOI] [PubMed]
Ruan W, Engevik MA, Spinler JK, Versalovic J. Healthy Human Gastrointestinal Microbiome: Composition and Function After a Decade of Exploration.Dig Dis Sci. 2020;65:695–705. [DOI] [PubMed]
Vasapolli R, Schütte K, Schulz C, Vital M, Schomburg D, Pieper DH, et al. Analysis of Transcriptionally Active Bacteria Throughout the Gastrointestinal Tract of Healthy Individuals.Gastroenterology. 2019;157:1081–92.e3. [DOI] [PubMed]
Gong J, Li L, Zuo X, Li Y. Change of the duodenal mucosa-associated microbiota is related to intestinal metaplasia.BMC Microbiol. 2019;19:275. [DOI] [PubMed] [PMC]
Sundin OH, Mendoza-Ladd A, Zeng M, Diaz-Arévalo D, Morales E, Fagan BM, et al. The human jejunum has an endogenous microbiota that differs from those in the oral cavity and colon.BMC Microbiol. 2017;17:160. [DOI] [PubMed] [PMC]
Zoetendal EG, Raes J, van den Bogert B, Arumugam M, Booijink CCGM, Troost FJ, et al. The human small intestinal microbiota is driven by rapid uptake and conversion of simple carbohydrates.ISME J. 2012;6:1415–26. [DOI] [PubMed] [PMC]
James KR, Gomes T, Elmentaite R, Kumar N, Gulliver EL, King HW, et al. Distinct microbial and immune niches of the human colon.Nat Immunol. 2020;21:343–53. [DOI] [PubMed] [PMC]
Dong S, Sun M, He C, Cheng H. Brain-gut-microbiota axis in Parkinson’s disease: A historical review and future perspective.Brain Res Bull. 2022;183:84–93. [DOI] [PubMed]
Ferreiro AL, Choi J, Ryou J, Newcomer EP, Thompson R, Bollinger RM, et al. Gut microbiome composition may be an indicator of preclinical Alzheimer’s disease.Sci Transl Med. 2023;15:eabo2984. [DOI] [PubMed] [PMC]
Bardenhorst SK, Cereda E, Severgnini M, Barichella M, Pezzoli G, Keshavarzian A, et al. Gut microbiota dysbiosis in Parkinson disease: A systematic review and pooled analysis.Eur J Neurol. 2023;30:3581–94. [DOI] [PubMed]
Sampson TR, Tansey MG, West AB, Liddle RA. Lewy body diseases and the gut.Mol Neurodegener. 2025;20:14. [DOI] [PubMed] [PMC]
Wasser CI, Mercieca E, Kong G, Hannan AJ, McKeown SJ, Glikmann-Johnston Y, et al. Gut dysbiosis in Huntington’s disease: associations among gut microbiota, cognitive performance and clinical outcomes.Brain Commun. 2020;2:fcaa110. [DOI] [PubMed] [PMC]
Zou B, Li J, Ma R, Cheng X, Ma R, Zhou T, et al. Gut Microbiota is an Impact Factor based on the Brain-Gut Axis to Alzheimer’s Disease: A Systematic Review.Aging Dis. 2023;14:964–1678. [DOI] [PubMed] [PMC]
Bostanciklioğlu M. The role of gut microbiota in pathogenesis of Alzheimer’s disease.J Appl Microbiol. 2019;127:954–67. [DOI] [PubMed]
Friedland RP, Chapman MR. The role of microbial amyloid in neurodegeneration.PLoS Pathog. 2017;13:e1006654. [DOI] [PubMed] [PMC]
Friedland RP. Mechanisms of molecular mimicry involving the microbiota in neurodegeneration.J Alzheimers Dis. 2015;45:349–62. [DOI] [PubMed]
Schwartz K, Boles BR. Microbial amyloids—functions and interactions within the host.Curr Opin Microbiol. 2013;16:93–9. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. Influence of human gut microbiome on the healthy and the neurodegenerative aging.Exp Gerontol. 2024;194:112497. [DOI] [PubMed]
Zhao Y, Jaber V, Lukiw WJ. Secretory Products of the Human GI Tract Microbiome and Their Potential Impact on Alzheimer’s Disease (AD): Detection of Lipopolysaccharide (LPS) in AD Hippocampus.Front Cell Infect Microbiol. 2017;7:318. [DOI] [PubMed] [PMC]
Zhan X, Stamova B, Sharp FR. Lipopolysaccharide Associates with Amyloid Plaques, Neurons and Oligodendrocytes in Alzheimer’s Disease Brain: A Review.Front Aging Neurosci. 2018;10:42. [DOI] [PubMed] [PMC]
Jia W, Rajani C, Kaddurah-Daouk R, Li H. Expert insights: The potential role of the gut microbiome-bile acid-brain axis in the development and progression of Alzheimer’s disease and hepatic encephalopathy.Med Res Rev. 2020;40:1496–507. [DOI] [PubMed]
Alsegiani AS, Shah ZA. The influence of gut microbiota alteration on age-related neuroinflammation and cognitive decline.Neural Regen Res. 2022;17:2407–12. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. Epigenetic Mechanisms in Aging: Extrinsic Factors and Gut Microbiome.Genes (Basel). 2024;15:1599. [DOI] [PubMed] [PMC]
Perea JR, Bolós M, Avila J. Microglia in Alzheimer’s Disease in the Context of Tau Pathology.Biomolecules. 2020;10:1439. [DOI] [PubMed] [PMC]
Xi J, Ding D, Zhu H, Wang R, Su F, Wu W, et al. Disturbed microbial ecology in Alzheimer’s disease: evidence from the gut microbiota and fecal metabolome.BMC Microbiol. 2021;21:226. [DOI] [PubMed] [PMC]
Cammann D, Lu Y, Cummings MJ, Zhang ML, Cue JM, Do J, et al. Genetic correlations between Alzheimer’s disease and gut microbiome genera.Sci Rep. 2023;13:5258. [DOI] [PubMed] [PMC]
Chen G, Zhou X, Zhu Y, Shi W, Kong L. Gut microbiome characteristics in subjective cognitive decline, mild cognitive impairment and Alzheimer’s disease: a systematic review and meta-analysis.Eur J Neurol. 2023;30:3568–80. [DOI] [PubMed]
Kumari S, Taliyan R, Dubey SK. Comprehensive Review on Potential Signaling Pathways Involving the Transfer of α-Synuclein from the Gut to the Brain That Leads to Parkinson’s Disease.ACS Chem Neurosci. 2023;14:590–602. [DOI] [PubMed]
Claudino Dos Santos JC, Oliveira LF, Noleto FM, Gusmão CTP, de Castro Brito GA, de Barros Viana GS. Gut-microbiome-brain axis: the crosstalk between the vagus nerve, alpha-synuclein and the brain in Parkinson’s disease.Neural Regen Res. 2023;18:2611–4. [DOI] [PubMed] [PMC]
Pant A, Bisht KS, Aggarwal S, Maiti TK. Human gut microbiota and Parkinson’s disease.Prog Mol Biol Transl Sci. 2022;192:281–307. [DOI] [PubMed]
Tansey MG, Wallings RL, Houser MC, Herrick MK, Keating CE, Joers V. Inflammation and immune dysfunction in Parkinson disease.Nat Rev Immunol. 2022;22:657–73. [DOI] [PubMed] [PMC]
Salim S, Ahmad F, Banu A, Mohammad F. Gut microbiome and Parkinson’s disease: Perspective on pathogenesis and treatment.J Adv Res. 2023;50:83–105. [PubMed] [PMC]
Qian Y, Yang X, Xu S, Wu C, Song Y, Qin N, et al. Alteration of the fecal microbiota in Chinese patients with Parkinson’s disease.Brain Behav Immun. 2018;70:194–202. [DOI] [PubMed]
Wallen ZD, Appah M, Dean MN, Sesler CL, Factor SA, Molho E, et al. Characterizing dysbiosis of gut microbiome in PD: evidence for overabundance of opportunistic pathogens.NPJ Parkinsons Dis. 2020;6:11. [DOI] [PubMed] [PMC]
Hirayama M, Ohno K. Parkinson’s Disease and Gut Microbiota.Ann Nutr Metab. 2021;77 Suppl 2:28–35. [DOI] [PubMed]
Rüb U, Seidel K, Heinsen H, Vonsattel JP, den Dunnen WF, Korf HW. Huntington’s disease (HD): the neuropathology of a multisystem neurodegenerative disorder of the human brain.Brain Pathol. 2016;26:726–40. [DOI] [PubMed] [PMC]
Wronka D, Karlik A, Misiorek JO, Przybyl L. What the Gut Tells the Brain-Is There a Link between Microbiota and Huntington’s Disease?Int J Mol Sci. 2023;24:4477. [DOI] [PubMed] [PMC]
Kong G, Cao KL, Judd LM, Li S, Renoir T, Hannan AJ. Microbiome profiling reveals gut dysbiosis in a transgenic mouse model of Huntington’s disease.Neurobiol Dis. 2020;135:104268. [DOI] [PubMed]
Mukherjea N, Khandelwal A, Saluja R, Kalra N. The Role of the human microbiome in neurodegenerative diseases: A Perspective.Curr Genet. 2025;71:17. [DOI] [PubMed]
Caputi V, Giron MC. Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson’s Disease.Int J Mol Sci. 2018;19:1689. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. Human oral microbiome and its influence on mental health and brain disorders.AIMS Microbiol. 2025;11:242–94. [DOI] [PubMed] [PMC]
Caselli E, Fabbri C, D’Accolti M, Soffritti I, Bassi C, Mazzacane S, et al. Defining the oral microbiome by whole-genome sequencing and resistome analysis: the complexity of the healthy picture.BMC Microbiol. 2020;20:120. [DOI] [PubMed] [PMC]
Verma D, Garg PK, Dubey AK. Insights into the human oral microbiome.Arch Microbiol. 2018;200:525–40. [DOI] [PubMed]
Cho Y, Kim K, Lee Y, Ku Y, Seol Y. Oral Microbiome and Host Health: Review on Current Advances in Genome-Wide Analysis.Appl Sci. 2021;11:4050. [DOI]
Li X, Liu Y, Yang X, Li C, Song Z. The Oral Microbiota: Community Composition, Influencing Factors, Pathogenesis, and Interventions.Front Microbiol. 2022;13:895537. [DOI] [PubMed] [PMC]
Murugesan S, Ahmad SFA, Singh P, Saadaoui M, Kumar M, Khodor SA. Profiling the Salivary microbiome of the Qatari population.J Transl Med. 2020;18:127. [DOI] [PubMed] [PMC]
Takeshita T, Kageyama S, Furuta M, Tsuboi H, Takeuchi K, Shibata Y, et al. Bacterial diversity in saliva and oral health-related conditions: the Hisayama Study.Sci Rep. 2016;6:22164. [DOI] [PubMed] [PMC]
Shaw L, Ribeiro ALR, Levine AP, Pontikos N, Balloux F, Segal AW, et al. The Human Salivary Microbiome Is Shaped by Shared Environment Rather than Genetics: Evidence from a Large Family of Closely Related Individuals.mBio. 2017;8:e01237–17. [DOI] [PubMed] [PMC]
Ren W, Zhang Q, Liu X, Zheng S, Ma L, Chen F, et al. Exploring the oral microflora of preschool children.J Microbiol. 2017;55:531–7. [DOI] [PubMed]
Simón-Soro A, Tomás I, Cabrera-Rubio R, Catalan MD, Nyvad B, Mira A. Microbial geography of the oral cavity.J Dent Res. 2013;92:616–21. [DOI] [PubMed]
Zhang Y, Wang X, Li H, Ni C, Du Z, Yan F. Human oral microbiota and its modulation for oral health.Biomed Pharmacother. 2018;99:883–93. [DOI] [PubMed]
Kozak M, Pawlik A. The Role of the Oral Microbiome in the Development of Diseases.Int J Mol Sci. 2023;24:5231. [DOI] [PubMed] [PMC]
Peng X, Cheng L, You Y, Tang C, Ren B, Li Y, et al. Oral microbiota in human systematic diseases.Int J Oral Sci. 2022;14:14. [DOI] [PubMed] [PMC]
Tiwari T, Kelly A, Randall CL, Tranby E, Franstve-Hawley J. Association Between Mental Health and Oral Health Status and Care Utilization.Front Oral Health. 2022;2:732882. [DOI] [PubMed] [PMC]
Skallevold HE, Rokaya N, Wongsirichat N, Rokaya D. Importance of oral health in mental health disorders: An updated review.J Oral Biol Craniofac Res. 2023;13:544–52. [DOI] [PubMed] [PMC]
Yu X, Yang J, Jin B, Xu H, Zhang H, Xiao J, et al. A strategy for bypassing the blood-brain barrier: Facial intradermal brain-targeted delivery via the trigeminal nerve.J Control Release. 2017;258:22–33. [DOI] [PubMed]
Narengaowa, Kong W, Lan F, Awan UF, Qing H, Ni J. The Oral-Gut-Brain AXIS: The Influence of Microbes in Alzheimer’s Disease.Front Cell Neurosci. 2021;15:633735. [DOI] [PubMed] [PMC]
Bowman GL, Dayon L, Kirkland R, Wojcik J, Peyratout G, Severin IC, et al. Blood-brain barrier breakdown, neuroinflammation, and cognitive decline in older adults.Alzheimers Dement. 2018;14:1640–50. [DOI] [PubMed]
Bowland GB, Weyrich LS. The Oral-Microbiome-Brain Axis and Neuropsychiatric Disorders: An Anthropological Perspective.Front Psychiatry. 2022;13:810008. [DOI] [PubMed] [PMC]
Bulgart HR, Neczypor EW, Wold LE, Mackos AR. Microbial involvement in Alzheimer disease development and progression.Mol Neurodegener. 2020;15:42. [DOI] [PubMed] [PMC]
Sansores-España LD, Melgar-Rodríguez S, Olivares-Sagredo K, Cafferata EA, Martínez-Aguilar VM, Vernal R, et al. Oral-Gut-Brain Axis in Experimental Models of Periodontitis: Associating Gut Dysbiosis With Neurodegenerative Diseases.Front Aging. 2021;2:781582. [DOI] [PubMed] [PMC]
Kitamoto S, Nagao-Kitamoto H, Hein R, Schmidt TM, Kamada N. The Bacterial Connection between the Oral Cavity and the Gut Diseases.J Dent Res. 2020;99:1021–9. [DOI] [PubMed] [PMC]
Maitre Y, Mahalli R, Micheneau P, Delpierre A, Amador G, Denis F. Evidence and Therapeutic Perspectives in the Relationship between the Oral Microbiome and Alzheimer’s Disease: A Systematic Review.Int J Environ Res Public Health. 2021;18:11157. [DOI] [PubMed] [PMC]
Chen C, Wu Y, Chang Y. Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study.Alzheimers Res Ther. 2017;9:56. [DOI] [PubMed] [PMC]
Dominy SS, Lynch C, Ermini F, Benedyk M, Marczyk A, Konradi A, et al. Porphyromonas gingivalis in Alzheimer’s disease brains: Evidence for disease causation and treatment with small-molecule inhibitors.Sci Adv. 2019;5:eaau3333. [DOI] [PubMed] [PMC]
Kanagasingam S, von Ruhland C, Welbury R, Chukkapalli SS, Singhrao SK. Porphyromonas gingivalis Conditioned Medium Induces Amyloidogenic Processing of the Amyloid-β Protein Precursor upon in vitro Infection of SH-SY5Y Cells.J Alzheimers Dis Rep. 2022;6:577–87. [DOI] [PubMed] [PMC]
Morikawa T, Uehara O, Paudel D, Yoshida K, Harada F, Hiraki D, et al. Systemic Administration of Lipopolysaccharide from Porphyromonas gingivalis Decreases Neprilysin Expression in the Mouse Hippocampus.In Vivo. 2023;37:163–72. [DOI] [PubMed] [PMC]
Grimm MOW, Mett J, Stahlmann CP, Haupenthal VJ, Zimmer VC, Hartmann T. Neprilysin and Aβ Clearance: Impact of the APP Intracellular Domain in NEP Regulation and Implications in Alzheimer’s Disease.Front Aging Neurosci. 2013;5:98. [DOI] [PubMed] [PMC]
Jungbauer G, Stähli A, Zhu X, Alberi LA, Sculean A, Eick S. Periodontal microorganisms and Alzheimer disease - A causative relationship?Periodontol 2000. 2022;89:59–82. [DOI] [PubMed] [PMC]
Díaz-Zúñiga J, Muñoz Y, Melgar-Rodríguez S, More J, Bruna B, Lobos P, et al. Serotype b of Aggregatibacter actinomycetemcomitans triggers pro-inflammatory responses and amyloid beta secretion in hippocampal cells: a novel link between periodontitis and Alzheimer’s disease?J Oral Microbiol. 2019;11:1586423. [DOI] [PubMed] [PMC]
Wu L, Su X, Tang Z, Jian L, Zhu H, Cheng X, et al. Treponema denticola Induces Neuronal Apoptosis by Promoting Amyloid-β Accumulation in Mice.Pathogens. 2022;11:1150. [DOI] [PubMed] [PMC]
Yan C, Diao Q, Zhao Y, Zhang C, He X, Huang R, et al. Fusobacterium nucleatum infection-induced neurodegeneration and abnormal gut microbiota composition in Alzheimer’s disease-like rats.Front Neurosci. 2022;16:884543. [DOI] [PubMed] [PMC]
Berthouzoz E, Lazarevic V, Zekeridou A, Castro M, Debove I, Aybek S, et al. Oral and intestinal dysbiosis in Parkinson’s disease.Rev Neurol (Paris). 2023;179:937–46. [DOI] [PubMed]
Li Z, Lu G, Luo E, Wu B, Li Z, Guo J, et al. Oral, Nasal, and Gut Microbiota in Parkinson’s Disease.Neuroscience. 2022;480:65–78. [DOI] [PubMed]
Bai X, Xu S, Zhou L, Meng X, Li Y, Chen Y, et al. Oral pathogens exacerbate Parkinson’s disease by promoting Th1 cell infiltration in mice.Microbiome. 2023;11:254. [DOI] [PubMed] [PMC]
Gan G, Chen R, Zheng P, Long K, Cheng KKY, Sulaiman JE, et al. Oral pathogens meet the gut microbiome: new mechanistic insights on systemic disease.Front Cell Infect Microbiol. 2026;15:1673512. [DOI] [PubMed] [PMC]
Li C, Fan Y, Chen X. Oral microbiota-driven immune modulation along the oral-gut axis: from local signals to systemic inflammation.NPJ Biofilms Microbiomes. 2026;12:46. [DOI] [PubMed] [PMC]
Xiao X, Zhang X, Wang J, Liu Y, Yan H, Xing X, et al. Proton pump inhibitors alter gut microbiota by promoting oral microbiota translocation: a prospective interventional study.Gut. 2024;73:1098–109. [DOI] [PubMed]
Mukherjee S, Chopra A, Karmakar S, Bhat SG. Periodontitis increases the risk of gastrointestinal dysfunction: An update on the plausible pathogenic molecular mechanisms.Crit Rev Microbiol. 2025;51:187–217. [DOI] [PubMed]
Hajishengallis G. Periodontitis: From microbial immune subversion to systemic inflammation.Nat Rev Immunol. 2015;15:30–44. [DOI] [PubMed] [PMC]
Skowron K, Bauza-Kaszewska J, Kraszewska Z, Wiktorczyk-Kapischke N, Grudlewska-Buda K, Kwiecińska-Piróg J, et al. Human Skin Microbiome: Impact of Intrinsic and Extrinsic Factors on Skin Microbiota.Microorganisms. 2021;9:543. [DOI] [PubMed] [PMC]
Cundell AM. Microbial Ecology of the Human Skin.Microb Ecol. 2018;76:113–20. [DOI] [PubMed]
Nguyen UT, Kalan LR. Forgotten fungi: the importance of the skin mycobiome.Curr Opin Microbiol. 2022;70:102235. [DOI] [PubMed] [PMC]
Hannigan GD, Meisel JS, Tyldsley AS, Zheng Q, Hodkinson BP, SanMiguel AJ, et al. The human skin double-stranded DNA virome: topographical and temporal diversity, genetic enrichment, and dynamic associations with the host microbiome.mBio. 2015;6:e01578–15. [DOI] [PubMed] [PMC]
Natarelli N, Gahoonia N, Sivamani RK. Bacteriophages and the Microbiome in Dermatology: The Role of the Phageome and a Potential Therapeutic Strategy.Int J Mol Sci. 2023;24:2695. [DOI] [PubMed] [PMC]
Borrego-Ruiz A, Borrego JJ. Microbial Dysbiosis in the Skin Microbiome and Its Psychological Consequences.Microorganisms. 2024;12:1908. [DOI] [PubMed] [PMC]
Wang P, Rajput D, Wang X, Huang C, Chen C. Exploring the possible relationship between skin microbiome and brain cognitive functions: a pilot EEG study.Sci Rep. 2024;14:7774. [DOI] [PubMed] [PMC]
Arikan M, Yildiz Z, Demir TK, Yilmaz NH, Sen A, Hanoglu L, et al. Axillary Microbiota Is Associated with Cognitive Impairment in Parkinson’s Disease Patients.Microbiol Spectr. 2022;10:e0235821. [DOI] [PubMed] [PMC]
Rahmdel S, Purkayastha M, Nega M, Liberini E, Li N, Luqman A, et al. Diversity of Neurotransmitter-Producing Human Skin Commensals.Int J Mol Sci. 2024;25:12345. [DOI] [PubMed] [PMC]
Zhou M, Xu R, Kaelber DC, Gurney ME. Tumor Necrosis Factor (TNF) blocking agents are associated with lower risk for Alzheimer’s disease in patients with rheumatoid arthritis and psoriasis.PLoS One. 2020;15:e0229819. [DOI] [PubMed] [PMC]
Pezzolo E, Mutlu U, Vernooij MW, Dowlatshahi EA, Gisondi P, Girolomoni G, et al. Psoriasis is not associated with cognition, brain imaging markers, and risk for dementia: The Rotterdam Study.J Am Acad Dermatol. 2021;85:671–80. [DOI] [PubMed]
Lemon KP. Human nasal microbiota.Curr Biol. 2020;30:R1118–9. [DOI] [PubMed]
Bell JS, Spencer JI, Yates RL, Yee SA, Jacobs BM, DeLuca GC. Invited Review: From nose to gut - the role of the microbiome in neurological disease.Neuropathol Appl Neurobiol. 2019;45:195–215. [DOI] [PubMed]
Pereira PAB, Aho VTE, Paulin L, Pekkonen E, Auvinen P, Scheperjans F. Oral and nasal microbiota in Parkinson’s disease.Parkinsonism Relat Disord. 2017;38:61–7. [DOI] [PubMed]
Yan M, Pamp SJ, Fukuyama J, Hwang PH, Cho D, Holmes S, et al. Nasal microenvironments and interspecific interactions influence nasal microbiota complexity and S. aureus carriage.Cell Host Microbe. 2013;14:631–40. [DOI] [PubMed] [PMC]
Zou Y, Lu D, Liu L, Zhang H, Zhou Y. Olfactory dysfunction in Alzheimer’s disease.Neuropsychiatr Dis Treat. 2016;12:869–75. [DOI] [PubMed] [PMC]
Thomann PA, Dos Santos V, Seidl U, Toro P, Essig M, Schröder J. MRI-derived atrophy of the olfactory bulb and tract in mild cognitive impairment and Alzheimer’s disease.J Alzheimers Dis. 2009;17:213–21. [DOI] [PubMed]
Maheshwari P, Eslick GD. Bacterial infection and Alzheimer’s disease: a meta-analysis.J Alzheimers Dis. 2015;43:957–66. [DOI] [PubMed]
Alao JO, Bamigboye FO. Nasal-gut microbiome axis in health and disease.Med Microecol. 2025;26:100153. [DOI]
Lazarini F, Roze E, Lannuzel A, Lledo P. The microbiome-nose-brain axis in health and disease.Trends Neurosci. 2022;45:718–21. [DOI] [PubMed]
Song H, Zou J, Sun Z, Pu Y, Qi W, Sun L, et al. Nasal microbiome in relation to olfactory dysfunction and cognitive decline in older adults.Transl Psychiatry. 2025;15:122. [DOI] [PubMed] [PMC]
Villar-Gómez N, Ojeda-Hernandez DD, López-Muguruza E, García-Flores S, Bonel-García N, Benito-Martín MS, et al. Nose-to-Brain: The Next Step for Stem Cell and Biomaterial Therapy in Neurological Disorders.Cells. 2022;11:3095. [DOI] [PubMed] [PMC]
Feigin VL, Vos T, Nichols E, Owolabi MO, Carroll WM, Dichgans M, et al. The global burden of neurological disorders: translating evidence into policy.Lancet Neurol. 2020;19:255–65. [DOI] [PubMed] [PMC]
Borrego-Ruiz A. Una Revisión Crítica sobre la Aplicación de Estimulación Cognitiva en el Contexto Gerontológico.Escr Psicol. 2024;17:31–43. [DOI]
Borrego Ruiz A, Bustillos López A. Intervención social dirigida al envejecimiento saludable: revisión de estudios recientes.AMC. 2024;50:21–38. [DOI]
Gadhave DG, Sugandhi VV, Jha SK, Nangare SN, Gupta G, Singh SK, et al. Neurodegenerative disorders: Mechanisms of degeneration and therapeutic approaches with their clinical relevance.Ageing Res Rev. 2024;99:102357. [DOI] [PubMed]
Borrego-Ruiz A, Borrego JJ. Determinants of Vaginal Microbiome Stability and Homeostasis.BIOCELL. 2025;49:1311–38. [DOI]
Wu P, Chen Y, Zhao J, Zhang G, Chen J, Wang J, et al. Urinary Microbiome and Psychological Factors in Women with Overactive Bladder.Front Cell Infect Microbiol. 2017;7:488. [DOI] [PubMed] [PMC]
Lu S, Zhao Q, Guan Y, Sun Z, Li W, Guo S, et al. The communication mechanism of the gut-brain axis and its effect on central nervous system diseases: A systematic review.Biomed Pharmacother. 2024;178:117207. [DOI] [PubMed]
Armengaud J. Metaproteomics to understand how microbiota function: The crystal ball predicts a promising future.Environ Microbiol. 2023;25:115–25. [DOI] [PubMed] [PMC]
Hill-Burns EM, Debelius JW, Morton JT, Wissemann WT, Lewis MR, Wallen ZD, et al. Parkinson’s disease and Parkinson’s disease medications have distinct signatures of the gut microbiome.Mov Disord. 2017;32:739–49. [DOI] [PubMed] [PMC]
