{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,4]],"date-time":"2026-11-04T23:24:49Z","timestamp":1793834689004,"version":"4.6.1"},"reference-count":85,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["214589\/Z\/18\/Z"],"award-info":[{"award-number":["214589\/Z\/18\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000833","name":"Rosetrees Trust","doi-asserted-by":"publisher","award":["M701"],"award-info":[{"award-number":["M701"]}],"id":[{"id":"10.13039\/501100000833","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosgenetics.org"],"crossmark-restriction":false},"short-container-title":["PLoS Genet"],"abstract":"<jats:p>\n                    Mutations in the\n                    <jats:italic>GBA1<\/jats:italic>\n                    gene cause the lysosomal storage disorder Gaucher disease (GD) and are the greatest known genetic risk factors for Parkinson\u2019s disease (PD). Communication between the gut and brain and immune dysregulation are increasingly being implicated in neurodegenerative disorders such as PD. Here, we show that flies lacking the\n                    <jats:italic>Gba1b<\/jats:italic>\n                    gene, the main fly orthologue of\n                    <jats:italic>GBA1<\/jats:italic>\n                    , display widespread NF\n                    <jats:italic>-k<\/jats:italic>\n                    B signalling activation, including gut inflammation, and brain glial activation. We also demonstrate intestinal autophagic defects, gut dysfunction, and microbiome dysbiosis. Remarkably, modulating the microbiome of\n                    <jats:italic>Gba1b<\/jats:italic>\n                    knockout flies, by raising them under germ-free conditions, partially ameliorates lifespan, locomotor and immune phenotypes. Moreover, we show that modulation of the immune deficiency (IMD) pathway is detrimental to the survival of\n                    <jats:italic>Gba1<\/jats:italic>\n                    deficient flies. We also reveal that direct stimulation of autophagy by rapamycin treatment achieves similar benefits to germ-free conditions independent of gut bacterial load. Consistent with this, we show that pharmacologically blocking autophagosomal-lysosomal fusion, mimicking the autophagy defects of\n                    <jats:italic>Gba1<\/jats:italic>\n                    depleted cells, is sufficient to stimulate intestinal immune activation. Overall, our data elucidate a mechanism whereby an altered microbiome, coupled with defects in autophagy, drive chronic activation of NF\n                    <jats:italic>-k<\/jats:italic>\n                    B signaling in\n                    <jats:italic>a Gba1<\/jats:italic>\n                    loss-of-function model. It also highlights that elimination of the microbiota or stimulation of autophagy to remove immune mediators, rather than prolonged immunosuppression, may represent effective therapeutic avenues for\n                    <jats:italic>GBA1-<\/jats:italic>\n                    associated disorders.\n                  <\/jats:p>","DOI":"10.1371\/journal.pgen.1011063","type":"journal-article","created":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T13:35:30Z","timestamp":1703165730000},"page":"e1011063","update-policy":"https:\/\/doi.org\/10.1371\/journal.pgen.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Autophagic dysfunction and gut microbiota dysbiosis cause chronic immune activation in a Drosophila model of Gaucher disease"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3819-2023","authenticated-orcid":true,"given":"Magda L.","family":"Atilano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9700-4926","authenticated-orcid":true,"given":"Alexander","family":"Hull","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catalina-Andreea","family":"Romila","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mirjam L.","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob","family":"Wildfire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4873-4735","authenticated-orcid":true,"given":"Enric","family":"Ure\u00f1a","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0845-662X","authenticated-orcid":true,"given":"Miranda","family":"Dyson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6324-2854","authenticated-orcid":true,"given":"Jorge","family":"Ivan-Castillo-Quan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Linda","family":"Partridge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2048-4332","authenticated-orcid":true,"given":"Kerri J.","family":"Kinghorn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"issue":"Suppl Suppl 1","key":"pgen.1011063.ref001","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/jnc.13385","article-title":"The relationship between glucocerebrosidase mutations and Parkinson disease","volume":"139 Suppl 1","author":"A Migdalska-Richards","year":"2016","journal-title":"J Neurochem"},{"issue":"Pt A","key":"pgen.1011063.ref002","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.mcn.2015.03.013","article-title":"Glucocerebrosidase and Parkinson disease: Recent advances","volume":"66","author":"AH Schapira","year":"2015","journal-title":"Mol Cell Neurosci"},{"key":"pgen.1011063.ref003","first-page":"299","article-title":"Gaucher disease: clinical profile and therapeutic developments.","volume":"4","author":"TM Cox","year":"2010","journal-title":"Biologics"},{"issue":"1","key":"pgen.1011063.ref004","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.neuron.2017.12.012","article-title":"Reversible Conformational Conversion of alpha-Synuclein into Toxic Assemblies by Glucosylceramide","volume":"97","author":"F Zunke","year":"2018","journal-title":"Neuron"},{"issue":"Pt 9","key":"pgen.1011063.ref005","doi-asserted-by":"crossref","first-page":"2648","DOI":"10.1093\/brain\/awv179","article-title":"Glucocerebrosidase activity in Parkinson\u2019s disease with and without GBA mutations","volume":"138","author":"RN Alcalay","year":"2015","journal-title":"Brain"},{"issue":"3","key":"pgen.1011063.ref006","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/ana.23614","article-title":"Glucocerebrosidase deficiency in substantia nigra of parkinson disease brains","volume":"72","author":"ME Gegg","year":"2012","journal-title":"Ann Neurol"},{"issue":"11","key":"pgen.1011063.ref007","doi-asserted-by":"crossref","first-page":"6469","DOI":"10.1073\/pnas.95.11.6469","article-title":"alpha-Synuclein in filamentous inclusions of Lewy bodies from Parkinson\u2019s disease and dementia with lewy bodies","volume":"95","author":"MG Spillantini","year":"1998","journal-title":"Proc Natl Acad Sci U S A"},{"issue":"6","key":"pgen.1011063.ref008","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/mds.28004","article-title":"Implications of the Gut Microbiome in Parkinson\u2019s Disease","volume":"35","author":"M Elfil","year":"2020","journal-title":"Mov Disord"},{"key":"pgen.1011063.ref009","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.parkreldis.2017.02.002","article-title":"Gut microbiota: Implications in Parkinson\u2019s disease","volume":"38","author":"A Parashar","year":"2017","journal-title":"Parkinsonism Relat Disord"},{"issue":"1","key":"pgen.1011063.ref010","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1017\/S0317167100012695","article-title":"Cytokine gene polymorphisms and Parkinson\u2019s disease: a meta-analysis","volume":"39","author":"K Chu","year":"2012","journal-title":"Can J Neurol Sci"},{"issue":"5","key":"pgen.1011063.ref011","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1093\/hmg\/dds492","article-title":"A pathway-based analysis provides additional support for an immune-related genetic susceptibility to Parkinson\u2019s disease","volume":"22","author":"International Parkinson\u2019s Disease Genomics C","year":"2013","journal-title":"Hum Mol Genet"},{"issue":"9766","key":"pgen.1011063.ref012","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1016\/S0140-6736(10)62345-8","article-title":"Imputation of sequence variants for identification of genetic risks for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies","volume":"377","author":"International Parkinson Disease Genomics C","year":"2011","journal-title":"Lancet"},{"issue":"9","key":"pgen.1011063.ref013","doi-asserted-by":"crossref","first-page":"1659","DOI":"10.1007\/s10072-015-2227-9","article-title":"Association of TLR4 gene polymorphisms with sporadic Parkinson\u2019s disease in a Han Chinese population","volume":"36","author":"J Zhao","year":"2015","journal-title":"Neurol Sci"},{"issue":"1","key":"pgen.1011063.ref014","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1111\/acel.12409","article-title":"Lysosomal storage and impaired autophagy lead to inflammasome activation in Gaucher macrophages","volume":"15","author":"E Aflaki","year":"2016","journal-title":"Aging Cell"},{"issue":"12","key":"pgen.1011063.ref015","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/nri3763","article-title":"Immunity in Drosophila melanogaster\u2014from microbial recognition to whole-organism physiology","volume":"14","author":"N Buchon","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"pgen.1011063.ref016","doi-asserted-by":"crossref","first-page":"697","DOI":"10.1146\/annurev.immunol.25.022106.141615","article-title":"The host defense of Drosophila melanogaster","volume":"25","author":"B Lemaitre","year":"2007","journal-title":"Annu Rev Immunol"},{"issue":"19","key":"pgen.1011063.ref017","first-page":"E1752","article-title":"Dnr1 mutations cause neurodegeneration in Drosophila by activating the innate immune response in the brain","volume":"110","author":"Y Cao","year":"2013","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pgen.1011063.ref018","doi-asserted-by":"crossref","first-page":"591803","DOI":"10.3389\/fimmu.2020.591803","article-title":"Interplay Between NLRP3 Inflammasome and Autophagy.","volume":"11","author":"M Biasizzo","year":"2020","journal-title":"Front Immunol."},{"issue":"D1","key":"pgen.1011063.ref019","doi-asserted-by":"crossref","first-page":"D809","DOI":"10.1093\/nar\/gkx976","article-title":"FlyAtlas 2: a new version of the Drosophila melanogaster expression atlas with RNA-Seq, miRNA-Seq and sex-specific data","volume":"46","author":"DP Leader","year":"2018","journal-title":"Nucleic Acids Res"},{"issue":"9","key":"pgen.1011063.ref020","doi-asserted-by":"crossref","DOI":"10.3390\/jcm8091420","article-title":"Drosophila melanogaster Mutated in its GBA1b Ortholog Recapitulates Neuronopathic Gaucher Disease.","volume":"8","author":"O Cabasso","year":"2019","journal-title":"J Clin Med."},{"issue":"3","key":"pgen.1011063.ref021","doi-asserted-by":"crossref","first-page":"e1005944","DOI":"10.1371\/journal.pgen.1005944","article-title":"Glucocerebrosidase Deficiency in Drosophila Results in alpha-Synuclein-Independent Protein Aggregation and Neurodegeneration.","volume":"12","author":"MY Davis","year":"2016","journal-title":"PLoS Genet."},{"issue":"46","key":"pgen.1011063.ref022","doi-asserted-by":"crossref","first-page":"11654","DOI":"10.1523\/JNEUROSCI.4527-15.2016","article-title":"A Drosophila Model of Neuronopathic Gaucher Disease Demonstrates Lysosomal-Autophagic Defects and Altered mTOR Signalling and Is Functionally Rescued by Rapamycin","volume":"36","author":"KJ Kinghorn","year":"2016","journal-title":"J Neurosci"},{"issue":"13","key":"pgen.1011063.ref023","first-page":"2712","article-title":"The contribution of mutant GBA to the development of Parkinson disease in Drosophila","volume":"25","author":"G Maor","year":"2016","journal-title":"Hum Mol Genet"},{"issue":"15","key":"pgen.1011063.ref024","doi-asserted-by":"crossref","first-page":"4768","DOI":"10.1523\/JNEUROSCI.5951-08.2009","article-title":"Ensheathing glia function as phagocytes in the adult Drosophila brain","volume":"29","author":"J Doherty","year":"2009","journal-title":"J Neurosci"},{"issue":"6","key":"pgen.1011063.ref025","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1016\/j.neuron.2006.04.028","article-title":"The Drosophila cell corpse engulfment receptor Draper mediates glial clearance of severed axons","volume":"50","author":"JM MacDonald","year":"2006","journal-title":"Neuron"},{"issue":"28","key":"pgen.1011063.ref026","doi-asserted-by":"crossref","first-page":"eabn3326","DOI":"10.1126\/sciadv.abn3326","article-title":"Neuronal activity induces glucosylceramide that is secreted via exosomes for lysosomal degradation in glia","volume":"8","author":"L Wang","year":"2022","journal-title":"Sci Adv"},{"key":"pgen.1011063.ref027","article-title":"A gene-specific T2A-GAL4 library for Drosophila.","volume":"7","author":"PT Lee","year":"2018","journal-title":"Elife"},{"key":"pgen.1011063.ref028","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.nbd.2012.09.007","article-title":"Colonic inflammation in Parkinson\u2019s disease","volume":"50","author":"D Devos","year":"2013","journal-title":"Neurobiol Dis"},{"issue":"1","key":"pgen.1011063.ref029","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.cmet.2010.12.010","article-title":"Enteric neurons and systemic signals couple nutritional and reproductive status with intestinal homeostasis","volume":"13","author":"P Cognigni","year":"2011","journal-title":"Cell Metab"},{"issue":"12","key":"pgen.1011063.ref030","doi-asserted-by":"crossref","first-page":"e28032","DOI":"10.1371\/journal.pone.0028032","article-title":"Increased intestinal permeability correlates with sigmoid mucosa alpha-synuclein staining and endotoxin exposure markers in early Parkinson\u2019s disease.","volume":"6","author":"CB Forsyth","year":"2011","journal-title":"PLoS One."},{"key":"pgen.1011063.ref031","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1016\/j.parkreldis.2018.02.022","article-title":"Fecal markers of intestinal inflammation and intestinal permeability are elevated in Parkinson\u2019s disease","volume":"50","author":"A Schwiertz","year":"2018","journal-title":"Parkinsonism Relat Disord"},{"key":"pgen.1011063.ref032","doi-asserted-by":"crossref","first-page":"e10956","DOI":"10.7554\/eLife.10956","article-title":"Sex difference in pathology of the ageing gut mediates the greater response of female lifespan to dietary restriction","volume":"5","author":"JC Regan","year":"2016","journal-title":"Elife"},{"issue":"3","key":"pgen.1011063.ref033","doi-asserted-by":"crossref","first-page":"363","DOI":"10.5056\/jnm19044","article-title":"Parkinson\u2019s Disease: The Emerging Role of Gut Dysbiosis, Antibiotics, Probiotics, and Fecal Microbiota Transplantation.","volume":"25","author":"SK Dutta","year":"2019","journal-title":"J Neurogastroenterol Motil."},{"key":"pgen.1011063.ref034","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1007\/978-3-319-90545-7","volume-title":"The Gut Microbiome in Health and Disease","author":"D. Heller","year":"2018","edition":"1"},{"issue":"1","key":"pgen.1011063.ref035","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1186\/s12974-019-1528-y","article-title":"Altered gut microbiota and inflammatory cytokine responses in patients with Parkinson\u2019s disease","volume":"16","author":"CH Lin","year":"2019","journal-title":"J Neuroinflammation"},{"issue":"3","key":"pgen.1011063.ref036","doi-asserted-by":"crossref","first-page":"222","DOI":"10.1038\/ni.1980","article-title":"Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome","volume":"12","author":"K Nakahira","year":"2011","journal-title":"Nat Immunol"},{"issue":"8","key":"pgen.1011063.ref037","doi-asserted-by":"crossref","DOI":"10.15252\/embj.201797858","article-title":"Attenuation of cGAS-STING signaling is mediated by a p62\/SQSTM1-dependent autophagy pathway activated by TBK1","volume":"37","author":"T Prabakaran","year":"2018","journal-title":"EMBO J"},{"issue":"4","key":"pgen.1011063.ref038","doi-asserted-by":"crossref","first-page":"110286","DOI":"10.1016\/j.celrep.2021.110286","article-title":"Selective autophagy controls innate immune response through a TAK1\/TAB2\/SH3PX1 axis","volume":"38","author":"P Tsapras","year":"2022","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1011063.ref039","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1038\/s41467-017-01287-9","article-title":"Kenny mediates selective autophagic degradation of the IKK complex to control innate immune responses.","volume":"8","author":"R Tusco","year":"2017","journal-title":"Nat Commun."},{"issue":"1","key":"pgen.1011063.ref040","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1016\/j.ymeth.2014.03.014","article-title":"Assays to monitor autophagy in Drosophila.","volume":"68","author":"C Mauvezin","year":"2014","journal-title":"Methods"},{"issue":"3","key":"pgen.1011063.ref041","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.molcel.2009.04.026","article-title":"A role for ubiquitin in selective autophagy","volume":"34","author":"V Kirkin","year":"2009","journal-title":"Mol Cell"},{"issue":"6","key":"pgen.1011063.ref042","doi-asserted-by":"crossref","first-page":"1065","DOI":"10.1083\/jcb.200711108","article-title":"Ref(2)P, the Drosophila melanogaster homologue of mammalian p62, is required for the formation of protein aggregates in adult brain.","volume":"180","author":"IP Nezis","year":"2008","journal-title":"J Cell Biol"},{"issue":"34","key":"pgen.1011063.ref043","doi-asserted-by":"crossref","first-page":"35274","DOI":"10.18632\/oncotarget.5895","article-title":"Rapamycin preserves gut homeostasis during Drosophila aging","volume":"6","author":"X Fan","year":"2015","journal-title":"Oncotarget"},{"issue":"1","key":"pgen.1011063.ref044","doi-asserted-by":"crossref","first-page":"7824","DOI":"10.1038\/s41598-019-44106-5","article-title":"Rapamycin modulates tissue aging and lifespan independently of the gut microbiota in Drosophila.","volume":"9","author":"JM Schinaman","year":"2019","journal-title":"Sci Rep"},{"key":"pgen.1011063.ref045","doi-asserted-by":"crossref","first-page":"4028","DOI":"10.1038\/ncomms5028","article-title":"iPSC-derived neurons from GBA1-associated Parkinson\u2019s disease patients show autophagic defects and impaired calcium homeostasis.","volume":"5","author":"DC Schondorf","year":"2014","journal-title":"Nat Commun"},{"issue":"8","key":"pgen.1011063.ref046","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1080\/15548627.2018.1474314","article-title":"Chloroquine inhibits autophagic flux by decreasing autophagosome-lysosome fusion.","volume":"14","author":"M Mauthe","year":"2018","journal-title":"Autophagy"},{"issue":"6220","key":"pgen.1011063.ref047","doi-asserted-by":"crossref","first-page":"1260419","DOI":"10.1126\/science.1260419","article-title":"Proteomics. Tissue-based map of the human proteome","volume":"347","author":"M Uhlen","year":"2015","journal-title":"Science"},{"issue":"10","key":"pgen.1011063.ref048","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/s41593-018-0242-x","article-title":"Microglia in neurodegeneration","volume":"21","author":"S Hickman","year":"2018","journal-title":"Nat Neurosci"},{"issue":"4","key":"pgen.1011063.ref049","doi-asserted-by":"crossref","first-page":"574","DOI":"10.1002\/ana.410240415","article-title":"Rate of cell death in parkinsonism indicates active neuropathological process","volume":"24","author":"PL McGeer","year":"1988","journal-title":"Ann Neurol"},{"issue":"2","key":"pgen.1011063.ref050","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/j.nbd.2005.08.002","article-title":"In vivo imaging of microglial activation with [11C](R)-PK11195 PET in idiopathic Parkinson\u2019s disease.","volume":"21","author":"A Gerhard","year":"2006","journal-title":"Neurobiol Dis"},{"issue":"3","key":"pgen.1011063.ref051","doi-asserted-by":"crossref","first-page":"774","DOI":"10.1002\/mds.28375","article-title":"Brain Microglial Activation Increased in Glucocerebrosidase (GBA) Mutation Carriers without Parkinson\u2019s disease.","volume":"36","author":"S Mullin","year":"2021","journal-title":"Mov Disord"},{"issue":"8","key":"pgen.1011063.ref052","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1007\/s12149-016-1099-2","article-title":"Extrastriatal spreading of microglial activation in Parkinson\u2019s disease: a positron emission tomography study.","volume":"30","author":"T Terada","year":"2016","journal-title":"Ann Nucl Med"},{"issue":"7","key":"pgen.1011063.ref053","doi-asserted-by":"crossref","first-page":"1375","DOI":"10.1093\/hmg\/ddr019","article-title":"Spatial and temporal correlation between neuron loss and neuroinflammation in a mouse model of neuronopathic Gaucher disease","volume":"20","author":"T Farfel-Becker","year":"2011","journal-title":"Hum Mol Genet"},{"issue":"9","key":"pgen.1011063.ref054","doi-asserted-by":"crossref","first-page":"1317","DOI":"10.1038\/s41591-018-0106-7","article-title":"Fetal gene therapy for neurodegenerative disease of infants","volume":"24","author":"G Massaro","year":"2018","journal-title":"Nat Med"},{"issue":"3","key":"pgen.1011063.ref055","doi-asserted-by":"crossref","DOI":"10.3390\/cells10030630","article-title":"The Uncovered Function of the Drosophila GBA1a-Encoded Protein.","volume":"10","author":"O Cabasso","year":"2021","journal-title":"Cells"},{"issue":"2","key":"pgen.1011063.ref056","first-page":"205","article-title":"Cytokines in Gaucher\u2019s disease","volume":"10","author":"V Barak","year":"1999","journal-title":"Eur Cytokine Netw"},{"issue":"7","key":"pgen.1011063.ref057","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1002\/mds.26563","article-title":"Serum immune markers and disease progression in an incident Parkinson\u2019s disease cohort (ICICLE-PD).","volume":"31","author":"CH Williams-Gray","year":"2016","journal-title":"Mov Disord"},{"issue":"5","key":"pgen.1011063.ref058","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1136\/gutjnl-2018-316844","article-title":"Role of TLR4 in the gut-brain axis in Parkinson\u2019s disease: a translational study from men to mice","volume":"68","author":"P Perez-Pardo","year":"2019","journal-title":"Gut"},{"key":"pgen.1011063.ref059","first-page":"306","article-title":"Abnormal lipopolysaccharide binding protein as marker of gastrointestinal inflammation in Parkinson disease","volume":"9","author":"GD Pal","year":"2015","journal-title":"Front Neurosci"},{"issue":"1","key":"pgen.1011063.ref060","first-page":"33","article-title":"Influence of Commensal Microbiota in Barrier Function of Intestinal Mucosal Epithelium.","volume":"1","author":"L Michie","year":"2019","journal-title":"Adv Res Endocrinol Metab."},{"issue":"5","key":"pgen.1011063.ref061","doi-asserted-by":"crossref","first-page":"e1006277","DOI":"10.1371\/journal.ppat.1006277","article-title":"Drosophila as a model for homeostatic, antibacterial, and antiviral mechanisms in the gut","volume":"13","author":"X Liu","year":"2017","journal-title":"PLoS Pathog"},{"issue":"3","key":"pgen.1011063.ref062","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1385\/MB:19:3:279","article-title":"The biology of endotoxin","volume":"19","author":"H Heine","year":"2001","journal-title":"Mol Biotechnol"},{"issue":"10","key":"pgen.1011063.ref063","article-title":"Glucosylceramide Changes Bacterial Metabolism and Increases Gram-Positive Bacteria through Tolerance to Secondary Bile Acids In Vitro.","volume":"23","author":"H Dai","year":"2022","journal-title":"Int J Mol Sci"},{"issue":"13","key":"pgen.1011063.ref064","doi-asserted-by":"crossref","first-page":"4611","DOI":"10.18632\/aging.102073","article-title":"The role of commensal microbes in the lifespan of Drosophila melanogaster.","volume":"11","author":"HY Lee","year":"2019","journal-title":"Aging (Albany NY)."},{"issue":"6","key":"pgen.1011063.ref065","doi-asserted-by":"crossref","DOI":"10.3390\/ijms19061689","article-title":"Microbiome-Gut-Brain Axis and Toll-Like Receptors in Parkinson\u2019s Disease.","volume":"19","author":"V Caputi","year":"2018","journal-title":"Int J Mol Sci."},{"issue":"1","key":"pgen.1011063.ref066","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3233\/JPD-191693","article-title":"A Pilot Microbiota Study in Parkinson\u2019s Disease Patients versus Control Subjects, and Effects of FTY720 and FTY720-Mitoxy Therapies in Parkinsonian and Multiple System Atrophy Mouse Models.","volume":"10","author":"G Vidal-Martinez","year":"2020","journal-title":"J Parkinsons Dis."},{"issue":"10","key":"pgen.1011063.ref067","doi-asserted-by":"crossref","first-page":"1656","DOI":"10.1016\/j.celrep.2015.08.004","article-title":"Distinct Shifts in Microbiota Composition during Drosophila Aging Impair Intestinal Function and Drive Mortality","volume":"12","author":"RI Clark","year":"2015","journal-title":"Cell Rep"},{"key":"pgen.1011063.ref068","doi-asserted-by":"crossref","first-page":"41802","DOI":"10.1038\/srep41802","article-title":"Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.","volume":"7","author":"T Harach","year":"2017","journal-title":"Sci Rep."},{"issue":"2","key":"pgen.1011063.ref069","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1136\/gutjnl-2018-317431","article-title":"Transfer of a healthy microbiota reduces amyloid and tau pathology in an Alzheimer\u2019s disease animal model","volume":"69","author":"MS Kim","year":"2020","journal-title":"Gut"},{"issue":"4","key":"pgen.1011063.ref070","doi-asserted-by":"crossref","first-page":"e0214985","DOI":"10.1371\/journal.pone.0214985","article-title":"A novel synbiotic delays Alzheimer\u2019s disease onset via combinatorial gut-brain-axis signaling in Drosophila melanogaster.","volume":"14","author":"S Westfall","year":"2019","journal-title":"PLoS One."},{"issue":"6","key":"pgen.1011063.ref071","doi-asserted-by":"crossref","first-page":"1469","DOI":"10.1016\/j.cell.2016.11.018","article-title":"Gut Microbiota Regulate Motor Deficits and Neuroinflammation in a Model of Parkinson\u2019s Disease","volume":"167","author":"TR Sampson","year":"2016","journal-title":"Cell"},{"issue":"1","key":"pgen.1011063.ref072","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1186\/s12974-019-1564-7","article-title":"The endotoxin hypothesis of neurodegeneration.","volume":"16","author":"GC Brown","year":"2019","journal-title":"J Neuroinflammation."},{"issue":"3","key":"pgen.1011063.ref073","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1016\/j.immuni.2009.08.009","article-title":"Immune responses to the microbiota at the intestinal mucosal surface","volume":"31","author":"BA Duerkop","year":"2009","journal-title":"Immunity"},{"issue":"3","key":"pgen.1011063.ref074","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1159\/000447252","article-title":"Increased Intestinal Permeability and Decreased Barrier Function: Does It Really Influence the Risk of Inflammation?","volume":"1","author":"H. Fukui","year":"2016","journal-title":"Inflamm Intest Dis."},{"issue":"1","key":"pgen.1011063.ref075","doi-asserted-by":"crossref","first-page":"11344","DOI":"10.1038\/s41598-018-29341-6","article-title":"Blast exposure elicits blood-brain barrier disruption and repair mediated by tight junction integrity and nitric oxide dependent processes","volume":"8","author":"AF Logsdon","year":"2018","journal-title":"Sci Rep"},{"issue":"3","key":"pgen.1011063.ref076","doi-asserted-by":"crossref","DOI":"10.3390\/insects11030188","article-title":"Two Roles for the Tenebrio molitor Relish in the Regulation of Antimicrobial Peptides and Autophagy-Related Genes in Response to Listeria monocytogenes","volume":"11","author":"M Keshavarz","year":"2020","journal-title":"Insects"},{"issue":"8","key":"pgen.1011063.ref077","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1016\/j.celrep.2018.10.076","article-title":"The NF-kappaB Factor Relish Regulates Atg1 Expression and Controls Autophagy","volume":"25","author":"A Nandy","year":"2018","journal-title":"Cell Rep"},{"issue":"1","key":"pgen.1011063.ref078","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"issue":"7","key":"pgen.1011063.ref079","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1093\/bioinformatics\/btt656","article-title":"featureCounts: an efficient general purpose program for assigning sequence reads to genomic features","volume":"30","author":"Y Liao","year":"2014","journal-title":"Bioinformatics"},{"issue":"12","key":"pgen.1011063.ref080","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"issue":"1","key":"pgen.1011063.ref081","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing.","volume":"57","author":"Benjamini","year":"1995","journal-title":"Journal of the Royal Statistical Society: Series B (Methodological)."},{"issue":"W1","key":"pgen.1011063.ref082","doi-asserted-by":"crossref","first-page":"W191","DOI":"10.1093\/nar\/gkz369","article-title":"g:Profiler: a web server for functional enrichment analysis and conversions of gene lists (2019 update).","volume":"47","author":"U Raudvere","year":"2019","journal-title":"Nucleic Acids Res"},{"issue":"14","key":"pgen.1011063.ref083","doi-asserted-by":"crossref","first-page":"2420","DOI":"10.1093\/hmg\/ddaa125","article-title":"PICALM rescues glutamatergic neurotransmission, behavioural function and survival in a Drosophila model of Abeta42 toxicity","volume":"29","author":"Y Yu","year":"2020","journal-title":"Hum Mol Genet"},{"key":"pgen.1011063.ref084","article-title":"A Protocol to Generate Germ Free Drosophila for Microbial Interaction Studies.","volume":"S1 001","author":"E.M. Sabat DJ","year":"2015","journal-title":"Advanced Techniques in Biology and Medicine"},{"issue":"4","key":"pgen.1011063.ref085","doi-asserted-by":"crossref","first-page":"2110","DOI":"10.1038\/nprot.2006.336","article-title":"A protocol for dissecting Drosophila melanogaster brains for live imaging or immunostaining.","volume":"1","author":"JS Wu","year":"2006","journal-title":"Nat Protoc"}],"container-title":["PLOS Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011063","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,11,6]],"date-time":"2024-11-06T12:05:28Z","timestamp":1730894728000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pgen.1011063"}},"subtitle":[],"editor":[{"given":"Gregory P.","family":"Copenhaver","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"editor"}]}],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":85,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2023,12,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pgen.1011063","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2022.12.15.520449","asserted-by":"object"}]},"ISSN":["1553-7404"],"issn-type":[{"value":"1553-7404","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]}}}