{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T12:08:42Z","timestamp":1792757322367,"version":"4.5.0"},"reference-count":50,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2025,9,28]],"date-time":"2025-09-28T00:00:00Z","timestamp":1759017600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.mdpi.com"],"crossmark-restriction":true},"short-container-title":["Neurology International"],"abstract":"<jats:p>Background: Alterations of the gut microbiota have been increasingly implicated in the pathogenesis of dementia through mechanisms involving systemic inflammation, immune dysregulation, and gut\u2013brain axis disruption. Clinical evidence, however, remains fragmented. Objectives: This systematic review aimed to characterize gut microbiota profiles in individuals with mild cognitive impairment (MCI) or Alzheimer\u2019s dementia (AD), explore mechanistic associations with neurodegeneration, and evaluate the impact of microbiota-targeted interventions on cognitive outcomes. Methods: Following PRISMA 2020 guidelines and a registered protocol (PROSPERO CRD420251074832), PubMed\/Medline was searched through May 2025. Eligible studies included randomized controlled trials (RCTs) and cohort and case\u2013control studies assessing microbiota composition or interventions in participants with MCI or AD. Results: Twenty-one studies were included (1 RCT, 20 observational; sample size 22\u2013302). Most used 16S rRNA sequencing; one used shotgun metagenomics. Across cohorts, MCI and AD patients consistently showed reduced short-chain fatty acid-producing bacteria (Faecalibacterium, Ruminococcaceae, Lachnospiraceae) and increased pro-inflammatory taxa (Escherichia\/Shigella, Enterobacteriaceae, Bacteroides). Several studies reported reduced microbial diversity. Specific taxa, including Akkermansia muciniphila and Faecalibacterium, were associated with amyloid burden, hippocampal atrophy, and cognitive decline. Environmental and dietary factors influenced microbial composition and cognition. The RCT reported that probiotic supplementation improved inflammatory markers and BDNF levels, although changes in microbiota composition were inconsistent. Conclusions: Gut dysbiosis is strongly associated with cognitive impairment and markers of neurodegeneration. Modulation of the microbiota through diet and probiotics emerges as a promising avenue for dementia prevention and management, though robust longitudinal and interventional studies are needed to confirm causality and therapeutic efficacy.<\/jats:p>","DOI":"10.3390\/neurolint17100155","type":"journal-article","created":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T10:49:34Z","timestamp":1759142974000},"page":"155","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Gut Microbiota, Mild Cognitive Impairment and Dementia: A Systematic Review"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-7866","authenticated-orcid":false,"given":"Claudio","family":"Tana","sequence":"first","affiliation":[{"name":"Internal Medicine Unit, Eastern Hospital, ASL Taranto, 74121 Taranto, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samanta","family":"Moffa","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, G. D\u2019Annunzio University of Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0899-9870","authenticated-orcid":false,"given":"Marco","family":"Tana","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, ASL Lanciano Vasto Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5866-3849","authenticated-orcid":false,"given":"Claudio","family":"Ucciferri","sequence":"additional","affiliation":[{"name":"Infectious Disease Clinic, ASL Lanciano Vasto Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Livia","family":"Moffa","sequence":"additional","affiliation":[{"name":"Infectious Disease Clinic, ASL Lanciano Vasto Chieti, 66100 Chieti, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,28]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"572","DOI":"10.1016\/S0140-6736(24)01296-0","article-title":"Dementia prevention, intervention, and care: 2024 report of the Lancet standing Commission","volume":"404","author":"Livingston","year":"2024","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"24","DOI":"10.12779\/dnd.2025.24.1.24","article-title":"Clinical Practice Guidelines for Dementia: Recommendations for the Pharmacological Treatment of Behavioral and Psychological Symptoms","volume":"24","author":"Byeon","year":"2025","journal-title":"Dement. Neurocogn. Disord."},{"key":"ref_3","unstructured":"(2025, April 01). World Alzheimer Reprr 2015. Available online: https:\/\/www.alzint.org\/u\/WorldAlzheimerReport2015.pdf."},{"key":"ref_4","unstructured":"(2025, April 01). Global Dementia Observatory. Available online: https:\/\/www.who.int\/data\/gho\/data\/themes\/global-dementia-observatory-gdo."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Fo\u0142ta, J., Rzepka, Z., and Wrze\u015bniok, D. (2025). The Role of Inflammation in Neurodegenerative Diseases: Parkinson\u2019s Disease, Alzheimer\u2019s Disease, and Multiple Sclerosis. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26115177"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Dhurandhar, Y., Tomar, S., Das, A., Prajapati, J.L., Singh, A.P., Bodake, S.H., and Namdeo, K.P. (2025). Chronic inflammation in obesity and neurodegenerative diseases: Exploring the link in disease onset and progression. Mol. Biol. Rep., 52.","DOI":"10.1007\/s11033-025-10509-z"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1016\/j.immuni.2019.12.003","article-title":"Microglia, Lifestyle Stress, and Neurodegeneration","volume":"52","author":"Madore","year":"2020","journal-title":"Immunity"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Meng, X., and D\u2019Arcy, C. (2012). Education and dementia in the context of the cognitive reserve hypothesis: A systematic review with meta-analyses and qualitative analyses. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0038268"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Cardona, M., and Andr\u00e9s, P. (2023). Are social isolation and loneliness associated with cognitive decline in ageing?. Front. Aging Neurosci., 15.","DOI":"10.3389\/fnagi.2023.1075563"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1497","DOI":"10.2147\/CIA.S139163","article-title":"Gut microbiota, cognitive frailty and dementia in older individuals: A systematic review","volume":"13","author":"Ticinesi","year":"2018","journal-title":"Clin. Interv. Aging"},{"key":"ref_11","first-page":"47","article-title":"Digestive disorders and Intestinal microbiota","volume":"89","author":"Nouvenne","year":"2018","journal-title":"Acta Biomed."},{"key":"ref_12","first-page":"52","article-title":"The impact of intestinal microbiota on bio-medical research: Definitions, techniques and physiology of a \u201cnew frontier\u201d","volume":"89","author":"Ticinesi","year":"2018","journal-title":"Acta Biomed."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2565","DOI":"10.1016\/j.clnu.2022.09.012","article-title":"The gut microbiome, mild cognitive impairment, and probiotics: A randomized clinical trial in middle-aged and older adults","volume":"41","author":"Aljumaah","year":"2022","journal-title":"Clin. Nutr."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.jalz.2019.07.002","article-title":"Mild cognitive impairment has similar alterations as Alzheimer\u2019s disease in gut microbiota","volume":"15","author":"Li","year":"2019","journal-title":"Alzheimers Dement."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1186\/s13195-025-01769-9","article-title":"Compositional and functional gut microbiota alterations in mild cognitive impairment: Links to Alzheimer\u2019s disease pathology","volume":"17","author":"Fan","year":"2025","journal-title":"Alzheimers Res. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1159\/000526947","article-title":"Association between Gut Microbiota with Mild Cognitive Impairment and Alzheimer\u2019s Disease in a Thai Population","volume":"22","author":"Wanapaisan","year":"2022","journal-title":"Neurodegener. Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"761","DOI":"10.3233\/JAD-240597","article-title":"Characterizing Gut Microbiota in Older Chinese Adults with Cognitive Impairment: A Cross-Sectional Study","volume":"101","author":"Wang","year":"2024","journal-title":"J. Alzheimers Dis."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Yamashiro, K., Takabayashi, K., Kamagata, K., Nishimoto, Y., Togashi, Y., Yamauchi, Y., Ogaki, K., Li, Y., Hatano, T., and Motoi, Y. (2024). Free water in gray matter linked to gut microbiota changes with decreased butyrate producers in Alzheimer\u2019s disease and mild cognitive impairment. Neurobiol. Dis., 193.","DOI":"10.1016\/j.nbd.2024.106464"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"McLeod, A., Penalver Bernabe, B., Xia, Y., Sanchez-Flack, J., Lamar, M., Schiffer, L., Castellanos, K., Fantuzzi, G., Maki, P., and Fitzgibbon, M. (2023). Comparing the gut microbiome of obese, African American, older adults with and without mild cognitive impairment. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0280211"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Saji, N., Murotani, K., Hisada, T., Tsuduki, T., Sugimoto, T., Kimura, A., Niida, S., Toba, K., and Sakurai, T. (2019). The relationship between the gut microbiome and mild cognitive impairment in patients without dementia: A cross-sectional study conducted in Japan. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-55851-y"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Zhu, Z., Ma, X., Wu, J., Xiao, Z., Wu, W., Ding, S., Zheng, L., Liang, X., Luo, J., and Ding, D. (2022). Altered Gut Microbiota and Its Clinical Relevance in Mild Cognitive Impairment and Alzheimer\u2019s Disease: Shanghai Aging Study and Shanghai Memory Study. Nutrients, 14.","DOI":"10.3390\/nu14193959"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.4014\/jmb.2305.05009","article-title":"Association between Mild Cognitive Impairment and Gut Microbiota in Elderly Korean Patients","volume":"33","author":"Kim","year":"2023","journal-title":"J. Microbiol. Biotechnol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1093\/ajcn\/nqab078","article-title":"Diet quality, gut microbiota, and microRNAs associated with mild cognitive impairment in middle-aged and elderly Chinese population","volume":"114","author":"Zhang","year":"2021","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13195-022-00977-x","article-title":"Combination of gut microbiota and plasma amyloid-\u03b2 as a potential index for identifying preclinical Alzheimer\u2019s disease: A cross-sectional analysis from the SILCODE study","volume":"14","author":"Sheng","year":"2022","journal-title":"Alzheimers Res. Ther."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"513","DOI":"10.3233\/JAD-210259","article-title":"Altered Gut Microbiota in Adults with Subjective Cognitive Decline: The SILCODE Study","volume":"82","author":"Sheng","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e42100","DOI":"10.1097\/MD.0000000000042100","article-title":"of the gut microbiome in Alzheimer disease and mild cognitive impairment among older adults in Uganda: A case-control study","volume":"104","author":"Lwere","year":"2025","journal-title":"Medicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e0000422","DOI":"10.1128\/msystems.00004-22","article-title":"Stratification of the Gut Microbiota Composition Landscape across the Alzheimer\u2019s Disease Continuum in a Turkish Cohort","volume":"7","author":"Bayraktar","year":"2022","journal-title":"mSystems"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6398","DOI":"10.1007\/s11356-023-31504-6","article-title":"Air particulate pollution exposure associated with impaired cognition via microbiota gut-brain axis: An evidence from rural elderly female in northwest China","volume":"31","author":"Yuan","year":"2024","journal-title":"Environ. Sci. Pollut. Res. Int."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"111524","DOI":"10.1016\/j.nut.2021.111524","article-title":"Relationship between the Japanese-style diet, gut microbiota, and dementia: A cross-sectional study","volume":"94","author":"Saji","year":"2022","journal-title":"Nutrition"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"107176","DOI":"10.1016\/j.parkreldis.2024.107176","article-title":"Taxonomic intestinal microbiota differences in Lewy body spectrum disease and cohabitant controls","volume":"129","author":"Teigen","year":"2024","journal-title":"Park. Relat. Disord."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"299","DOI":"10.3233\/JAD-201040","article-title":"Gut Microbiome Features of Chinese Patients Newly Diagnosed with Alzheimer\u2019s Disease or Mild Cognitive Impairment","volume":"80","author":"Guo","year":"2021","journal-title":"J. Alzheimers Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"633","DOI":"10.1016\/j.bbi.2019.05.008","article-title":"Altered microbiomes distinguish Alzheimer\u2019s disease from amnestic mild cognitive impairment and health in a Chinese cohort","volume":"80","author":"Liu","year":"2019","journal-title":"Brain Behav. Immun."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"5578958","DOI":"10.1155\/2021\/5578958","article-title":"Elderly Patients with Mild Cognitive Impairment Exhibit Altered Gut Microbiota Profiles","volume":"2021","author":"Pan","year":"2021","journal-title":"J. Immunol. Res."},{"key":"ref_34","first-page":"4","article-title":"The intestinal microbiome and its relevance for functionality in older persons","volume":"22","author":"Ticinesi","year":"2019","journal-title":"Curr. Opin. Clin. Nutr. Metab. Care"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1053\/j.gastro.2025.02.035","article-title":"Machine Learning and Artificial Intelligence in the Multi-Omics Approach to Gut Microbiota","volume":"169","author":"Rozera","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1093\/gerona\/glac195","article-title":"Polypharmacy With High Drug Burden Index (DBI) Alters the Gut Microbiome Overriding Aging Effects and Is Reversible With Deprescribing","volume":"78","author":"Gemikonakli","year":"2023","journal-title":"J. Gerontol. A Biol. Sci. Med. Sci."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Hu, S., Song, J., Jiang, H., Wei, B., and Wang, H. (2025). Association between the dietary index for gut microbiota and cardiometabolic multimorbidity: Systemic immune-inflammation index and systemic inflammatory response index. Front. Nutr., 12.","DOI":"10.3389\/fnut.2025.1591799"},{"key":"ref_38","first-page":"e41559","article-title":"Understanding the Role of the Gut Microbiome in Diabetes and Therapeutics Targeting Leaky Gut: A Systematic Review","volume":"15","author":"Sadagopan","year":"2023","journal-title":"Cureus"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1038\/s41581-022-00654-0","article-title":"The gut microbiome and hypertension","volume":"19","author":"Zheng","year":"2023","journal-title":"Nat. Rev. Nephrol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3837","DOI":"10.3748\/wjg.v27.i25.3837","article-title":"Gut microbiota in obesity","volume":"27","author":"Liu","year":"2021","journal-title":"World J. Gastroenterol."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Pedroza Matute, S., and Iyavoo, S. (2023). Exploring the gut microbiota: Lifestyle choices, disease associations, and personal genomics. Front. Nutr., 10.","DOI":"10.3389\/fnut.2023.1225120"},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Sejbuk, M., Siebieszuk, A., and Witkowska, A.M. (2024). The Role of Gut Microbiome in Sleep Quality and Health: Dietary Strategies for Microbiota Support. Nutrients, 16.","DOI":"10.3390\/nu16142259"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3831972","DOI":"10.1155\/2017\/3831972","article-title":"Exercise Modifies the Gut Microbiota with Positive Health Effects","volume":"2017","author":"Monda","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Ticinesi, A., Nouvenne, A., Cerundolo, N., Catania, P., Prati, B., Tana, C., and Meschi, T. (2019). Gut Microbiota, Muscle Mass and Function in Aging: A Focus on Physical Frailty and Sarcopenia. Nutrients, 11.","DOI":"10.3390\/nu11071633"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Prokopidis, K., Chambers, E., Ni Lochlainn, M., and Witard, O.C. (2021). Mechanisms Linking the Gut-Muscle Axis With Muscle Protein Metabolism and Anabolic Resistance: Implications for Older Adults at Risk of Sarcopenia. Front. Physiol., 12.","DOI":"10.3389\/fphys.2021.770455"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"110639","DOI":"10.1016\/j.exger.2019.110639","article-title":"Gut microbiota and physical frailty through the mediation of sarcopenia","volume":"124","author":"Casati","year":"2019","journal-title":"Exp. Gerontol."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Ticinesi, A., Mancabelli, L., Tagliaferri, S., Nouvenne, A., Milani, C., Del Rio, D., Lauretani, F., Maggio, M.G., Ventura, M., and Meschi, T. (2020). The Gut-Muscle Axis in Older Subjects with Low Muscle Mass and Performance: A Proof of Concept Study Exploring Fecal Microbiota Composition and Function with Shotgun Metagenomics Sequencing. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21238946"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Ticinesi, A., Lauretani, F., Milani, C., Nouvenne, A., Tana, C., Del Rio, D., Maggio, M., Ventura, M., and Meschi, T. (2017). Aging Gut Microbiota at the Cross-Road between Nutrition, Physical Frailty, and Sarcopenia: Is There a Gut-Muscle Axis?. Nutrients, 9.","DOI":"10.3390\/nu9121303"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"109718","DOI":"10.1016\/j.neuropharm.2023.109718","article-title":"Gut-muscle-brain axis: Molecular mechanisms in neurodegenerative disorders and potential therapeutic efficacy of probiotic supplementation coupled with exercise","volume":"240","author":"Morella","year":"2023","journal-title":"Neuropharmacology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/s41392-024-01743-1","article-title":"Microbiota-gut-brain axis and its therapeutic applications in neurodegenerative diseases","volume":"9","author":"Loh","year":"2024","journal-title":"Signal Transduct. Target. Ther."}],"container-title":["Neurology International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/10\/155\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,29]],"date-time":"2025-09-29T12:01:44Z","timestamp":1759147304000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2035-8377\/17\/10\/155"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,28]]},"references-count":50,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["neurolint17100155"],"URL":"https:\/\/doi.org\/10.3390\/neurolint17100155","relation":{},"ISSN":["2035-8377"],"issn-type":[{"value":"2035-8377","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,28]]}}}