{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T18:01:28Z","timestamp":1790359288878,"version":"4.1.0"},"reference-count":73,"publisher":"Public Library of Science (PLoS)","issue":"9","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA217970"],"award-info":[{"award-number":["R01 CA217970"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["U01 CA167551"],"award-info":[{"award-number":["U01 CA167551"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01 CA076366"],"award-info":[{"award-number":["R01 CA076366"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:sec id=\"sec001\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Growing evidence links the gut microbiome to colorectal cancer (CRC) progression, with certain bacterial species enriched in specific molecular tumor subtypes. DNA mismatch repair deficiency in CRC, evidenced by the presence of microsatellite instability (MSI), has been consistently associated with a favorable prognosis, and may be related to certain aspects of the microbiome. Here, we examined the relationship between tumor microbial biodiversity and MSI status.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec002\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Diagnostic tumor tissue samples were obtained from the Seattle site of the Colon Cancer Family Registry (SCCFR) and a companion study; both recruited patients diagnosed with incident CRC from 1998 to 2007. MSI status assessment and prokaryotic\n                      <jats:italic>16S rRNA<\/jats:italic>\n                      gene sequencing was performed on the tumor tissue samples. We used an adaptive test of alpha-diversity (aMiAD) to estimate the association between microbial biodiversity and MSI status. We performed differential abundance analysis with ANCOM-BC to identify enriched genera in tumor tissue, based on dichotomized MSI status. Analyses were adjusted for age, sex, smoking history, and tumor location (N\u2009=\u2009632).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec003\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The adaptive aMiAD effect estimate was \u22121.08 (p\u2009=\u20090.29), suggesting that MSI-high tumors had lower estimated alpha-diversity, though this difference was not statistically significant. We identified 20 differentially abundant genera in CRC tumors according to MSI status, with 8 enriched genera and 12 depleted genera in MSI-high tumors. The most strongly enriched genera in MSI-high tumors were\n                      <jats:italic>Gemella<\/jats:italic>\n                      and\n                      <jats:italic>Lawsonella<\/jats:italic>\n                      , while\n                      <jats:italic>Sporolactobacillaceae<\/jats:italic>\n                      and\n                      <jats:italic>Cloacibacterium<\/jats:italic>\n                      were the most strongly depleted\n                      <jats:italic>. Fusobacterium<\/jats:italic>\n                      was enriched in MSI-high tumors only after subsetting the genus to\n                      <jats:italic>Fusobacterium nucleatum<\/jats:italic>\n                      specific sequences.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec id=\"sec004\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We did not detect a statistically significant association between the adaptive alpha-diversity measure and MSI status, though individual measures concordantly estimated a depletion of alpha-diversity in the MSI-high tumors. We found evidence of differential abundance of certain genera dependent on MSI status, including several novel associations.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1371\/journal.pone.0359555","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:34:29Z","timestamp":1790357669000},"page":"e0359555","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Tumor microbial biodiversity and microsatellite instability in colorectal cancer"],"prefix":"10.1371","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-5177-2186","authenticated-orcid":true,"given":"Calen","family":"Mendall","sequence":"first","affiliation":[{"name":"University of Washington","place":["Seattle, Washington, United States of America"],"department":["Department of Epidemiology, School of Public Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meredith A. J.","family":"Hullar","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keith R.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Courtney M.","family":"Hill","sequence":"additional","affiliation":[{"name":"University of Washington","place":["Seattle, Washington, United States of America"],"department":["Department of Epidemiology, School of Public Health"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9515-3277","authenticated-orcid":true,"given":"Claire E.","family":"Thomas","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4014-5947","authenticated-orcid":true,"given":"Ningxin","family":"Ma","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Clinical Research Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy W.","family":"Randolph","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Clinical Research Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7262-9029","authenticated-orcid":true,"given":"Rachel C.","family":"Malen","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana M.","family":"Reedy","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"LaBrie","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5439-1500","authenticated-orcid":true,"given":"John D.","family":"Potter","sequence":"additional","affiliation":[{"name":"University of Washington","place":["Seattle, Washington, United States of America"],"department":["Department of Epidemiology, School of Public Health"]},{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]},{"name":"Massey University","place":["Wellington, New Zealand"],"department":["Centre for Public Health Research"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuji","family":"Ogino","sequence":"additional","affiliation":[{"name":"Harvard T.H. Chan School of Public Health","place":["Boston, Massachusetts, United States of America"],"department":["Department of Epidemiology"]},{"name":"Brigham and Women\u2019s Hospital and Harvard Medical School","place":["Boston, Massachusetts, United States of America"],"department":["Department of Pathology"]},{"name":"Broad Institute of MIT and Harvard","place":["Cambridge, Massachusetts, United States of America"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Polly A.","family":"Newcomb","sequence":"additional","affiliation":[{"name":"Fred Hutchinson Cancer Center","place":["Seattle, Washington, United States of America"],"department":["Public Health Sciences Division"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4864-8351","authenticated-orcid":true,"given":"Amanda I.","family":"Phipps","sequence":"additional","affiliation":[{"name":"University of Washington","place":["Seattle, Washington, United States of 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