{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T05:49:06Z","timestamp":1793512146658,"version":"4.5.0"},"reference-count":118,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T00:00:00Z","timestamp":1694563200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Over the last few decades, a growing body of evidence has suggested a role for various infectious agents in Alzheimer\u2019s disease (AD) pathogenesis. Despite diverse pathogens (virus, bacteria, fungi) being detected in AD subjects\u2019 brains, research has focused on individual pathogens and only a few studies investigated the hypothesis of a bacterial brain microbiome. We profiled the bacterial communities present in non-demented controls and AD subjects\u2019 brains.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We obtained postmortem samples from the brains of 32 individual subjects, comprising 16 AD and 16 control age-matched subjects with a total of 130 samples from the frontal and temporal lobes and the entorhinal cortex. We used full-length 16S rRNA gene amplification with Pacific Biosciences sequencing technology to identify bacteria. We detected bacteria in the brains of both cohorts with the principal bacteria comprising\n                      <jats:italic>Cutibacterium acnes<\/jats:italic>\n                      (formerly\n                      <jats:italic>Propionibacterium acnes<\/jats:italic>\n                      ) and two species each of\n                      <jats:italic>Acinetobacter<\/jats:italic>\n                      and\n                      <jats:italic>Comamonas<\/jats:italic>\n                      genera. We used a hierarchical Bayesian method to detect differences in relative abundance among AD and control groups. Because of large abundance variances, we also employed a new analysis approach based on the Latent Dirichlet Allocation algorithm, used in computational linguistics. This allowed us to identify five sample classes, each revealing a different microbiota. Assuming that samples represented infections that began at different times, we ordered these classes in time, finding that the last class exclusively explained the existence or non-existence of AD.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      The AD-related pathogenicity of the brain microbiome seems to be based on a complex polymicrobial dynamic. The time ordering revealed a rise and fall of the abundance of\n                      <jats:italic>C. acnes<\/jats:italic>\n                      with pathogenicity occurring for an off-peak abundance level in association with at least one other bacterium from a set of genera that included\n                      <jats:italic>Methylobacterium<\/jats:italic>\n                      ,\n                      <jats:italic>Bacillus<\/jats:italic>\n                      ,\n                      <jats:italic>Caulobacter<\/jats:italic>\n                      ,\n                      <jats:italic>Delftia<\/jats:italic>\n                      , and\n                      <jats:italic>Variovorax<\/jats:italic>\n                      .\n                      <jats:italic>C. acnes<\/jats:italic>\n                      may also be involved with outcompeting the\n                      <jats:italic>Comamonas<\/jats:italic>\n                      species, which were strongly associated with non-demented brain microbiota, whose early destruction could be the first stage of disease. Our results are also consistent with a leaky blood\u2013brain barrier or lymphatic network that allows bacteria, viruses, fungi, or other pathogens to enter the brain.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2023.1123228","type":"journal-article","created":{"date-parts":[[2023,9,13]],"date-time":"2023-09-13T17:52:26Z","timestamp":1694627546000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":29,"title":["Evidence supportive of a bacterial component in the etiology for Alzheimer\u2019s disease and for a temporal-spatial development of a pathogenic microbiome in the brain"],"prefix":"10.3389","volume":"13","author":[{"given":"Yves","family":"Mon\u00e9","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua P.","family":"Earl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaros\u0142aw E.","family":"Kr\u00f3l","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Azad","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bhaswati","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garth D.","family":"Ehrlich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey R.","family":"Lapides","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,9,13]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1002\/alz.12068","article-title":"2020 Alzheimer\u2019s disease facts and figures","volume":"16","year":"2020","journal-title":"Alzheimer\u2019s Dement"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s12868-019-0489-5","article-title":"Astrocytes infected with Chlamydia pneumoniae demonstrate altered expression and activity of secretases involved in the generation of ?-amyloid found in Alzheimer disease","volume":"20","author":"Al-Atrache","year":"2019","journal-title":"BMC Neurosci."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1027","DOI":"10.1016\/j.neuron.2019.12.031","article-title":"Human herpesvirus 6 detection in Alzheimer\u2019s Disease cases and controls across multiple cohorts","volume":"105","author":"Allnutt","year":"2020","journal-title":"Neuron"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.3389\/fnins.2019.00171","article-title":"Searching for bacteria in neural tissue from amyotrophic lateral sclerosis","volume":"13","author":"Alonso","year":"2019","journal-title":"Front. 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