{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T06:00:27Z","timestamp":1782280827817,"version":"3.54.5"},"posted":{"date-parts":[[2025,2,22]]},"group-title":"Neuroscience","reference-count":68,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T00:00:00Z","timestamp":1740182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,2,22]]},"abstract":"<jats:title>SUMMARY<\/jats:title>\n                <jats:p>\n                  The native microbiome influences a plethora of host processes, including neurological function. However, its impacts on diverse brain cell types remains poorly understood. Here, we performed single nucleus RNA sequencing on hippocampi from wildtype, germ-free mice and reveal the microbiome-dependent transcriptional landscape across all major neural cell types. We found conserved impacts on key adaptive immune and neurodegenerative transcriptional pathways, underscoring the microbiome\u2019s contributions to disease-relevant processes. Mono-colonization with select indigenous microbes identified species-specific effects on the transcriptional state of brain myeloid cells. Colonization by\n                  <jats:italic>Escherichia coli<\/jats:italic>\n                  induced a distinct adaptive immune and neurogenerative disease-associated cell state, suggesting increased disease susceptibility. Indeed,\n                  <jats:italic>E. coli<\/jats:italic>\n                  exposure in the 5xFAD mouse model resulted in exacerbated cognitive decline and amyloid pathology, demonstrating its sufficiency to worsen Alzheimer\u2019s disease-relevant outcomes. Together, these results emphasize the broad, species-specific, microbiome-dependent consequences on neurological transcriptional state and highlight the capacity of specific microbes to modulate disease susceptibility.\n                <\/jats:p>\n                <jats:sec>\n                  <jats:title>Highlights<\/jats:title>\n                  <jats:list list-type=\"bullet\">\n                    <jats:list-item>\n                      <jats:p>The microbiome impacts the transcriptional landscape of all major brain cell types.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>Discrete microbes specifically modulate resident myeloid cell status.<\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Gut\n                        <jats:italic>E. coli<\/jats:italic>\n                        triggers dynamic transcriptional responses across neural cell types.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                    <jats:list-item>\n                      <jats:p>\n                        Exposure to\n                        <jats:italic>E. coli<\/jats:italic>\n                        exacerbates behavioral and cellular pathologies in 5xFAD mice.\n                      <\/jats:p>\n                    <\/jats:list-item>\n                  <\/jats:list>\n                <\/jats:sec>","DOI":"10.1101\/2025.02.17.638718","type":"posted-content","created":{"date-parts":[[2025,2,22]],"date-time":"2025-02-22T20:25:21Z","timestamp":1740255921000},"source":"Crossref","is-referenced-by-count":1,"title":["Indigenous gut microbes modulate neural cell state and neurodegenerative disease susceptibility"],"prefix":"10.64898","author":[{"given":"Lisa","family":"Blackmer-Raynolds","sequence":"first","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maureen M.","family":"Sampson","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Kozlov","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndsey","family":"Lipson","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam M.","family":"Hamilton","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean D.","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj","family":"Chopra","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjun","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, Emory University School of Medicine, Atlanta GA 30322"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven A.","family":"Sloan","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Emory 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