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Recent evidence posits that PD may initiate in the gut by microbes or their toxins that promote chronic gut inflammation that will ultimately impact the brain. In this work, we sought to demonstrate that the effects of the microbial toxin \u03b2-<jats:italic>N<\/jats:italic>-methylamino-L-alanine (BMAA) in the gut may trigger some PD cases, which is especially worrying as this toxin is present in certain foods but not routinely monitored by public health authorities.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>To test the hypothesis, we treated wild-type mice, primary neuronal cultures, cell lines and isolated mitochondria with BMAA, and analysed its impact on gut microbiota composition, barrier permeability, inflammation and aSyn aggregation as well as in brain inflammation, dopaminergic neuronal loss and motor behaviour. To further examine the key role of mitochondria, we also determined the specific effects of BMAA on mitochondrial function and on inflammasome activation.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>BMAA induced extensive depletion of segmented filamentous bacteria (SFB) that regulate gut immunity, thus triggering gut dysbiosis, immune cell migration, increased intestinal inflammation, loss of barrier integrity and caudo-rostral progression of aSyn. Additionally, BMAA induced <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic> mitochondrial dysfunction with cardiolipin exposure and consequent activation of neuronal innate immunity. These events primed neuroinflammation, dopaminergic neuronal loss and motor deficits.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Taken together, our results demonstrate that chronic exposure to dietary BMAA can trigger a chain of events that recapitulate the evolution of the PD pathology from the gut to the brain, which is consistent with \u2018gut-first\u2019 PD.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/gutjnl-2021-326023","type":"journal-article","created":{"date-parts":[[2021,11,26]],"date-time":"2021-11-26T13:25:29Z","timestamp":1637933129000},"page":"73-89","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":54,"title":["Footprints of a microbial toxin from the gut microbiome to mesencephalic mitochondria"],"prefix":"10.1136","volume":"72","author":[{"given":"A 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Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"PDBEB\u2013Ph.D. Programme in Experimental Biology and Biomedicine, Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal"}]},{"given":"A Raquel","family":"Pereira-Santos","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology and CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"PDBEB\u2013Ph.D. Programme in Experimental Biology and Biomedicine, Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal"}]},{"given":"I Luisa","family":"Ferreira","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology and CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal"}]},{"given":"Susana","family":"Alarico","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology and CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, Portugal"}]},{"given":"Igor","family":"Tiago","sequence":"additional","affiliation":[{"name":"CFE-Centre for Functional Ecology, Department of Life Sciences, University of Coimbra, Coimbra, Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8938-7560","authenticated-orcid":false,"given":"Nuno","family":"Empadinhas","sequence":"additional","affiliation":[{"name":"CNC-Center for Neuroscience and Cell Biology and CIBB-Center for Innovative Biomedicine and Biotechnology, University of Coimbra, Coimbra, Portugal"},{"name":"IIIUC-Institute of Interdisciplinary Research, University of Coimbra, Coimbra, 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