{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T04:02:22Z","timestamp":1787889742004,"version":"build-2784847793"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Increasing evidence suggests a potential role of the gut microbiota in Parkinson\u2019s disease (PD). However, the relationship between the gut microbiome (GM) and PD dementia (PDD) remains debated, with their causal effects and underlying mechanisms not yet fully understood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Utilizing data from large-scale genome-wide association studies (GWASs), this study applied bidirectional and mediating Mendelian randomization (MR) to investigate the causal relationship and underlying mechanisms between the GM and PDD. In our analysis, inverse-variance weighting (IVW) was used as the primary method. Clinical validation was performed using metagenomic sequencing and bioinformatic analysis. The relationships between the GM and PDD were visualized using receiver operating characteristic (ROC) curves, confusion matrices, and correlation analyses.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our study revealed a significant causal impact of five GM genera, 10 metabolites, two metabolite ratios, and 22 immune cells on PDD. Notably, the maltose to sucrose ratio was identified as a mediator of the positive causal effect of <jats:italic>Subdoligranulum<\/jats:italic> on PDD, with a mediation value of 13.2%. The clinical samples confirmed the efficacy of <jats:italic>Subdoligranulum<\/jats:italic> sp. in distinguishing patients with PDD from normal controls (area under the curve (AUC)\u202f=\u202f0.80, 95% CI: 0.674\u20130.924). In addition, correlation analysis revealed a potential negative association between <jats:italic>Subdoligranulum<\/jats:italic> abundance and the Mini-Mental State Examination (MMSE) scores (r\u202f=\u202f\u22120.316, <jats:italic>p<\/jats:italic>\u202f=\u202f0.006). Finally, bioinformatic analysis suggested that <jats:italic>Subdoligranulum<\/jats:italic> may influence PDD risk through the regulation of starch and sucrose metabolism pathways.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Our study confirms the potential role of <jats:italic>Subdoligranulum<\/jats:italic> in PDD progression, potentially mediated through starch and sucrose metabolism. These findings highlight the importance of the gut\u2013brain axis in PDD and may provide insights into targeted interventions for PDD.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2025.1620449","type":"journal-article","created":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T11:52:32Z","timestamp":1756122752000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Effects of gut microbiota on cognitive impairment in Parkinson\u2019s disease: a comprehensive Mendelian randomization and case\u2013control study"],"prefix":"10.3389","volume":"16","author":[{"given":"Yukun","family":"Feng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Xie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xueyang","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiguo","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41531-024-00687-1","article-title":"Gut microbiome is not associated with mild cognitive impairment in parkinson's disease","volume":"10","author":"Aho","year":"2024","journal-title":"NPJ Parkinsons Dis."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.neulet.2005.11.012","article-title":"Gastric alpha-synuclein immunoreactive inclusions in meissner's and Auerbach's plexuses in cases staged for parkinson's disease-related brain pathology","volume":"396","author":"Braak","year":"2006","journal-title":"Neurosci. 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