{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T18:56:18Z","timestamp":1781636178259,"version":"3.54.5"},"reference-count":49,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Parkinson's disease with motor complications (PD\u2010MC) lacks effective diagnostic and therapeutic strategies. The perturbations of the gut microbiota and plasma metabolites are closely associated with the etiopathogenesis of PD. However, whether fecal microbiome dysbiosis and changed plasma metabolites are involved in PD progression, particularly in the development of PD\u2010MC, is still unclear.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this study, we performed an extensive multiomics analysis involving 108 PD patients for 16S rRNA gut microbiome profiling and 246 PD patients for plasma nontargeted metabolomics. Our findings revealed distinct gut microbiota and plasma metabolites associated with PD\u2010MC. Utilizing these discriminative features, we developed a multivariate diagnostic model for PD\u2010MC. The relationships between differential metabolites and microorganisms were evaluated using Spearman correlation analysis. Functional interpretation of the key metabolites was conducted through enrichment and pathway analysis, employing the KEGG and SMPDB databases.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>PD\u2010MC patients had distinct gut microbial signatures as compared with PD without motor complications (PD\u2010NMC) individuals and were increased in fecal Lactobacillus, Limosilactobacillus, Bifidobacterium, and Ligilactobacillus genera along with depleted Agathobacter. Moreover, metabolomic analysis revealed the differences in plasma 3\u2010deoxysappanchalcone (3\u2010DSC), 1,3\u2010Dimethyluracil (1,3\u2010DTl), Leucine, and N\u2010Acetylisoleucine (N\u2010AIL), Dodec\u20106\u2010enoic acid (D\u20106\u2010E), N\u2010butyl Oleate (N\u2010BO), and 4\u2010hydroxyundecanoic acid (4\u2010HUA) in PD\u2010MC compared to PD\u2010NMC. Spearman correlation analysis showed that the fecal microbiota aberrations in PD\u2010MC patients were linked to plasma metabolic changes, indicating the association between key microbial populations and metabolomic profiles in PD\u2010MC.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study underscores the value of employing integrated multiomics profiling of the fecal microbiome and plasma metabolome to enhance the mechanistic understanding of PD\u2010MC and to identify potential diagnostic biomarkers.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns.70750","type":"journal-article","created":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T08:55:27Z","timestamp":1769158527000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Exploring the Fecal Microbiome Dysbiosis and Its Plasma Metabolome Determinants in Advanced Parkinson's Disease With Motor Complications"],"prefix":"10.1002","volume":"32","author":[{"given":"Shuangjie","family":"Qian","sequence":"first","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jialong","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Duan","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiwei","family":"Quan","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaxue","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keke","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Qian","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3462-1879","authenticated-orcid":false,"given":"Hongchang","family":"Gao","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Science Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Oujiang Laboratory  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1132-0179","authenticated-orcid":false,"given":"Chenglong","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Neurology The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Key Laboratory of Alzheimer's Disease of Zhejiang Province, Institute of Aging Wenzhou Medical University  Wenzhou Zhejiang China"},{"name":"Department of Geriatrics, Geriatric Medical Center The First Affiliated Hospital of Wenzhou Medical University  Wenzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"e_1_2_14_2_1","first-page":"148","article-title":"Are Dopaminergic Neurons Selectively Vulnerable to Parkinson's Disease?","volume":"60","author":"Agid Y.","year":"1993","journal-title":"Advances in Neurology"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2019.22360"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27261"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-1931(00)00031-8"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570159X14666151208114634"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pneurobio.2015.07.002"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-022-00681-2"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrneurol.2015.197"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-34667-x"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30356-4"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000013225"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2019.06.003"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-019-1528-y"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2016.11.018"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-023-00628-1"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2021.12.012"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-018-0304-2"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27173"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.25555"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13024-021-00425-8"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21669-4"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.4155\/bio-2016-0111"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-022-11739-y"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/2041-210X.12114"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1010184"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscentsci.2c01468"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12859-019-3310-7"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/2047-217X-2-13"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12920-020-00826-6"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp1002"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2018.04.004"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.3390\/metabo12121222"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.arr.2017.09.006"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/6686037"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41531-023-00612-y"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0191670"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8010027"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-025-05306-5"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom15010149"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.26431"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.27802"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.22340"},{"key":"e_1_2_14_44_1","doi-asserted-by":"publisher","DOI":"10.1177\/10738584211011979"},{"key":"e_1_2_14_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth.2604"},{"key":"e_1_2_14_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks1219"},{"key":"e_1_2_14_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.ede.0000147512.81966.ba"},{"key":"e_1_2_14_48_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11306-007-0082-2"},{"key":"e_1_2_14_49_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.analchem.8b01482"},{"key":"e_1_2_14_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkac963"}],"container-title":["CNS Neuroscience &amp; Therapeutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70750","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cns.70750","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns.70750","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,15]],"date-time":"2026-02-15T10:58:55Z","timestamp":1771153135000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns.70750"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1]]},"references-count":49,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2026,1]]}},"alternative-id":["10.1002\/cns.70750"],"URL":"https:\/\/doi.org\/10.1002\/cns.70750","archive":["Portico"],"relation":{},"ISSN":["1755-5930","1755-5949"],"issn-type":[{"value":"1755-5930","type":"print"},{"value":"1755-5949","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1]]},"assertion":[{"value":"2025-09-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-05","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-01-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70750"}}