{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:23:51Z","timestamp":1791923031075,"version":"4.3.4"},"reference-count":61,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100018071","name":"OHSU Knight Cancer Institute","doi-asserted-by":"crossref","award":["CCSG CPCP-2023-002"],"award-info":[{"award-number":["CCSG CPCP-2023-002"]}],"id":[{"id":"10.13039\/100018071","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Men treated with androgen deprivation therapy (ADT) for prostate cancer are at risk for cognitive decline. Patient genetics and endocrine state may shape gut microbiome features that relate to cognition. Methods: We studied a subsample of 79 prostate cancer survivors with prior ADT exposure previously enrolled in a randomized controlled exercise trial comparing three training modalities (strength training, Tai Chi training, or stretching control) who completed an additional food-frequency questionnaire and remote Montreal Cognitive Assessment (MoCA) and provided saliva and stool for APOE genotyping, salivary testosterone, and 16S rRNA sequencing. We used beta regression for MoCA (scaled 0\u20131), linear models for testosterone, alpha diversity regressions, PERMANOVA for beta diversity, and DESeq2 for genus-level differential abundance, with false-discovery correction. Results: Compared to post-stretching control, post-strength training testing was associated with higher MoCA scores whereas post-Tai Chi testing was not. APOE \u03b54 carriers exhibited a greater testosterone increase with strength training than non-carriers. Testosterone, and its interactions with exercise modality and APOE \u03b52 status, was related to presence\/absence-based community structure; APOE \u03b54 interacted with exercise intervention to influence alpha diversity. At the genus level, exercise was linked to lower levels of Bacteroidota taxa (including Muribaculaceae) and higher levels of Enterobacteriaceae; APOE \u03b54 status was linked to higher Megamonas and lower Rikenellaceae RC9 levels; and higher salivary testosterone levels were linked to higher Prevotellaceae taxa and Succinivibrio levels. Higher MoCA scores were associated with lower abundances of several Firmicutes genera. Conclusions: Endocrine state and APOE genotype may condition the gut microbiome\u2019s response to exercise intervention in ADT-treated prostate cancer survivors, with downstream associations with cognition. These findings could inform precision survivorship strategies pairing strength training with genotype- and hormone-informed microbiome monitoring to optimize cognitive performance.<\/jats:p>","DOI":"10.3390\/genes16121507","type":"journal-article","created":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T12:47:26Z","timestamp":1765889246000},"page":"1507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Exercise, APOE Genotype, and Testosterone Modulate Gut Microbiome\u2013Cognition Associations in Prostate Cancer Survivors"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9861-9893","authenticated-orcid":false,"given":"Jacob","family":"Raber","sequence":"first","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Departments of Neurology and Radiation Medicine, Division of Neuroscience, ONPRC, Oregon Health & Science University, Portland, OR 97239, USA"},{"name":"Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-7815-6242","authenticated-orcid":false,"given":"Abigail","family":"O\u2019Niel","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin D.","family":"Kasschau","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Pederson","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naomi","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Behavioral Neuroscience, Oregon Health & Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7587-3426","authenticated-orcid":false,"given":"Carolyn","family":"Guidarelli","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"Division of Oncological Sciences, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Chalmers","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"Division of Oncological Sciences, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1706-8020","authenticated-orcid":false,"given":"Kerri","family":"Winters-Stone","sequence":"additional","affiliation":[{"name":"Knight Cancer Institute, Oregon Health and Science University, Portland, OR 97239, USA"},{"name":"Division of Oncological Sciences, School of Medicine, Oregon Health and Science University, Portland, OR 97239, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas J.","family":"Sharpton","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Department of Statistics, Oregon State University, Corvallis, OR 97331, USA"},{"name":"Linus Pauling Institute, Oregon State University, Corvallis, OR 97331, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,16]]},"reference":[{"key":"ref_1","first-page":"363","article-title":"Cancer treatment and survivorship statistics","volume":"69","author":"Miller","year":"2019","journal-title":"CA Cancer J. 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