{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,29]],"date-time":"2025-11-29T05:26:50Z","timestamp":1764394010197,"version":"3.46.0"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T00:00:00Z","timestamp":1764201600000},"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":"crossref","award":["82071257","82371254"],"award-info":[{"award-number":["82071257","82371254"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Tongzhou District, Beijing Medical and Health Industry Development Project","award":["JX2023YJ021"],"award-info":[{"award-number":["JX2023YJ021"]}]},{"name":"Taishan Young Scholars","award":["tsqn202306029"],"award-info":[{"award-number":["tsqn202306029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Parkinson\u2019s disease (PD) and type 2 diabetes mellitus (T2DM) exhibit increasing comorbidity, yet the shared contribution of gut microbiota remains unclear. To investigate parallel microbial and functional alterations underlying PD, T2DM, and PD with diabetes (PDDM), we performed fecal metagenomic sequencing in 156 PD, 41 T2DM, and 44 PD with diabetes (PDDM) patients and 83 healthy controls (HC). PD and T2DM showed highly concordant microbial shifts, with 22 genera and 91 species consistently altered across disease groups compared with HC. Functional enrichment highlighted common perturbations in taurine and hypotaurine metabolism, retinol metabolism, the hypoxia-inducible factor-1 (HIF-1) pathway, and xenobiotic degradation, implicating disrupted oxidative stress responses, neuro-metabolic regulation, and detoxification. Key taxa, including Limosilactobacillus fermentum, Lactobacillus porci, and Lactobacillus delbrueckii, were increased and showed moderate positive correlations (|\u03c1| \u2265 0.3) with antioxidant\/retinol\u2013HIF-1, taurine\u2013hypotaurine, and xenobiotic degradation pathways. Bifidobacterium breve (unadjusted analysis) was increased in PD and further enriched in PDDM, correlating with multiple beneficial pathways. Bifidobacterium simiarum (covariate-adjusted analyses) showed the broadest positive pathway associations, while selected Bacteroides species (e.g., B. acidifaciens) exhibited negative correlations with insulin-resistance pathways and positive correlations with steroid hormone biosynthesis. By contrast, Butyricimonas vaginalis showed negative correlations with HIF-1 and insulin signaling and with cytochrome P450-related drug metabolism. These findings provide the first systematic evidence of parallel taxonomic and functional dysbiosis in PD and T2DM, supporting gut microbiota as a shared mediator and potential therapeutic target in comorbidity.<\/jats:p>","DOI":"10.3390\/microorganisms13122705","type":"journal-article","created":{"date-parts":[[2025,11,27]],"date-time":"2025-11-27T10:25:16Z","timestamp":1764239116000},"page":"2705","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Shared Gut Microbial and Functional Signatures Linking Parkinson\u2019s Disease and Type 2 Diabetes Revealed by Function-Anchored Metagenomics"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-7668-2131","authenticated-orcid":false,"given":"Ying","family":"Cui","sequence":"first","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shiya","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenlu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yitong","family":"Du","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bingyu","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingkai","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojiao","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Anzhen Hospital, Capital Medical University, Beijing 100013, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sichen","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolong","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinran","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yingying","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7585-310X","authenticated-orcid":false,"given":"Shuangjiang","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-7712","authenticated-orcid":false,"given":"Yulin","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3211-3037","authenticated-orcid":false,"given":"Houzhen","family":"Tuo","sequence":"additional","affiliation":[{"name":"Department of Neurology, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1016\/S1474-4422(18)30295-3","article-title":"Global, regional, and national burden of Parkinson\u2019s disease, 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