{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T22:31:54Z","timestamp":1791325914281,"version":"4.3.1"},"reference-count":120,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T00:00:00Z","timestamp":1746489600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Laboratory Directed Research and Development Program of Oak Ridge National Laboratory"},{"name":"the University of Tennessee\u2019s College of Nursing and the Department of Chemistry"},{"name":"the University of Tennessee Office of Research, Innovation, and Economic Development\u2019s Human Health and Wellbeing Project"},{"name":"ALS Research at the University of Tennessee Medical Center"},{"name":"Cole Center for Parkinson\u2019s Disease and Movement Disorders"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Neurodegenerative diseases (NDDs) are multifactorial disorders frequently associated with gut dysbiosis, oxidative stress, and inflammation; however, the pathophysiological mechanisms remain poorly understood. Methods: Using untargeted mass spectrometry-based metabolomics and 16S sequencing of human stool, we investigated bacterial and metabolic dyshomeostasis in the gut microbiome associated with early disease stages across three NDDs\u2014amyotrophic lateral sclerosis (ALS), Alzheimer\u2019s disease (AD), Parkinson\u2019s disease (PD)\u2014and healthy controls (HC). Results: We discovered a previously unrecognized link between a microbial-derived metabolite with an unknown role in human physiology, 2,3-dihydroxypropane-1-sulfonate (DHPS), and gut dysbiosis in NDDs. DHPS was downregulated in AD, ALS, and PD, while bacteria involved in DHPS metabolism, Eubacterium and Desulfovibrio, were increased in all disease cohorts. Additionally, select taxa within the Clostridia class had strong negative correlations to DHPS, suggesting a potential role in DHPS metabolism. A catabolic product of DHPS is hydrogen sulfide, and when in excess, it is known to promote inflammation, oxidative stress, mitochondrial damage, and gut dysbiosis, known hallmarks of NDDs. Conclusions: These findings suggest that cryptic sulfur metabolism via DHPS is a potential missing link in our current understanding of gut dysbiosis associated with NDD onset and progression. As this was a hypothesis generating study, more work is needed to elucidate the role of DHPS in gut dysbiosis and neurodegenerative diseases.<\/jats:p>","DOI":"10.3390\/nu17091597","type":"journal-article","created":{"date-parts":[[2025,5,6]],"date-time":"2025-05-06T11:38:06Z","timestamp":1746531486000},"page":"1597","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Specific Bacterial Taxa and Their Metabolite, DHPS, May Be Linked to Gut Dyshomeostasis in Patients with Alzheimer\u2019s Disease, Parkinson\u2019s Disease, and Amyotrophic Lateral Sclerosis"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8387-4779","authenticated-orcid":false,"given":"Courtney","family":"Christopher","sequence":"first","affiliation":[{"name":"Department of Chemistry, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3673-5570","authenticated-orcid":false,"given":"Katherine","family":"Morgan","sequence":"additional","affiliation":[{"name":"College of Nursing, University of Tennessee, Knoxville, TN 37996, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Tolleson","sequence":"additional","affiliation":[{"name":"The Cole Center for Parkinson\u2019s and Movement Disorders, The University of Tennessee Medical Center, Knoxville, TN 37922, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Randall","family":"Trudell","sequence":"additional","affiliation":[{"name":"The Cole Center for Parkinson\u2019s and Movement Disorders, The University of Tennessee Medical Center, Knoxville, TN 37922, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Fernandez-Romero","sequence":"additional","affiliation":[{"name":"The Pat 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