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Clark Fund for ALS Research"},{"DOI":"10.13039\/100017644","name":"Sinai Medical Staff Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100017644","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Scott L. Pranger ALS Clinic Fund"},{"DOI":"10.13039\/100008456","name":"A. Alfred Taubman Medical Research Institute","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100008456","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NeuroNetwork for Emerging Therapies"},{"DOI":"10.13039\/100007270","name":"University of Michigan","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007270","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Amyotrophic lateral sclerosis (ALS) is a complex, fatal neurodegenerative disease. Disease pathophysiology is incompletely understood but evidence suggests gut dysbiosis occurs in ALS, linked to impaired gastrointestinal integrity, immune system dysregulation and altered metabolism. Gut microbiome and plasma metabolome have been separately investigated in ALS, but little is known about gut microbe-plasma metabolite correlations, which could identify robust disease biomarkers and potentially shed mechanistic insight. Here, gut microbiome changes were longitudinally profiled in ALS and correlated to plasma metabolome. Gut microbial structure at the phylum level differed in ALS versus control participants, with differential abundance of several distinct genera. Unsupervised clustering of microbe and metabolite levels identified modules, which differed significantly in ALS versus control participants. Network analysis found several prominent amplicon sequence variants strongly linked to a group of metabolites, primarily lipids. Similarly, identifying the features that contributed most to case versus control separation pinpointed several bacteria correlated to metabolites, predominantly lipids. Mendelian randomization indicated possible causality from specific lipids related to fatty acid and acylcarnitine metabolism. Overall, the results suggest ALS cases and controls differ in their gut microbiome, which correlates with plasma metabolites, particularly lipids, through specific genera. These findings have the potential to identify robust disease biomarkers and shed mechanistic insight into ALS.<\/jats:p>","DOI":"10.1093\/brain\/awad306","type":"journal-article","created":{"date-parts":[[2023,9,15]],"date-time":"2023-09-15T20:40:09Z","timestamp":1694810409000},"page":"665-679","source":"Crossref","is-referenced-by-count":42,"title":["Gut microbiome correlates with plasma lipids in amyotrophic lateral sclerosis"],"prefix":"10.1093","volume":"147","author":[{"given":"Kai","family":"Guo","sequence":"first","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia","family":"Figueroa-Romero","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohamed H","family":"Noureldein","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin J","family":"Murdock","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masha G","family":"Savelieff","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota , Grand Forks, ND 58202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junguk","family":"Hur","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of North Dakota , Grand Forks, ND 58202 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8780-6637","authenticated-orcid":false,"given":"Stephen A","family":"Goutman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9162-2694","authenticated-orcid":false,"given":"Eva L","family":"Feldman","sequence":"additional","affiliation":[{"name":"Department of Neurology, University of Michigan , Ann Arbor, MI 48109 , USA"},{"name":"NeuroNetwork for Emerging Therapies, University of Michigan , Ann Arbor, MI 48109 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,9,18]]},"reference":[{"key":"2024020201465217700_awad306-B1","doi-asserted-by":"crossref","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","article-title":"Amyotrophic lateral sclerosis","volume":"400","author":"Feldman","year":"2022","journal-title":"Lancet"},{"key":"2024020201465217700_awad306-B2","doi-asserted-by":"crossref","first-page":"480","DOI":"10.1016\/S1474-4422(21)00465-8","article-title":"Recent advances in the diagnosis and prognosis of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol"},{"key":"2024020201465217700_awad306-B3","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1016\/S1474-4422(21)00414-2","article-title":"Emerging insights into the complex genetics and pathophysiology of amyotrophic lateral sclerosis","volume":"21","author":"Goutman","year":"2022","journal-title":"Lancet Neurol"},{"key":"2024020201465217700_awad306-B4","doi-asserted-by":"crossref","first-page":"821","DOI":"10.1097\/EDE.0000000000000381","article-title":"Commentary: Mapping the human exposome: Without it, how can we find environmental risk factors for ALS?","volume":"26","author":"Al-Chalabi","year":"2015","journal-title":"Epidemiology"},{"key":"2024020201465217700_awad306-B5","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1186\/s12916-020-01885-3","article-title":"The gut microbiome: A key player in the complexity of amyotrophic lateral sclerosis (ALS)","volume":"19","author":"Boddy","year":"2021","journal-title":"BMC Med"},{"key":"2024020201465217700_awad306-B6","doi-asserted-by":"crossref","first-page":"428","DOI":"10.3389\/fnins.2020.00428","article-title":"Potential preventive strategies for amyotrophic lateral 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