{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T11:05:29Z","timestamp":1790593529130,"version":"4.1.0"},"reference-count":90,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T00:00:00Z","timestamp":1790553600000},"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. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      We observed the elevation of\n                      <jats:italic>p<\/jats:italic>\n                      -cresol in the untargeted metabolome of the multiomics portion of the NASA Twins Study of One Year in Space.\n                      <jats:italic>p<\/jats:italic>\n                      -Cresol is a uremic and neurotoxin that is produced via the metabolism of dietary tyrosine by gut bacteria. Intestinally produced\n                      <jats:italic>p<\/jats:italic>\n                      -cresol is absorbed into systemic circulation where it exerts its adverse metabolic effects and drives phenotypic changes relevant to astronauts, including the brain, heart, bone, liver, kidney, and colon.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A pair of monozygotic twins were studied for 25 months, during which one subject spent 340 days aboard the International Space Station (ISS), while his identical twin remained on Earth. Molecular analyses included genome, epigenome, transcriptome, proteome, metabolome, immunome, and microbiome. Our metabolite feature extraction was focused on plasma\n                      <jats:italic>p<\/jats:italic>\n                      -cresol (\n                      <jats:italic>p<\/jats:italic>\n                      -cresyl sulfate [pCS] and\n                      <jats:italic>p<\/jats:italic>\n                      -cresol glucuronide [pCG]), along with associated biological dynamics that govern\n                      <jats:italic>p<\/jats:italic>\n                      -cresol production and metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Significance was observed for pCG when comparing Post-flight vs. Inflight (adj p = 0.016). pCS values were significantly altered Post-flight vs. Inflight (adj p = 0.002) and Post-flight vs. Late-flight (adj p = 0.037). pCS values for Early-flight vs. Pre-flight approached significance (adj p = 0.08). In alignment with elevated plasma\n                      <jats:italic>p<\/jats:italic>\n                      -cresol values at certain stages of spaceflight, we found an increase in count-normalized abundance (raw reads) for the major\n                      <jats:italic>p<\/jats:italic>\n                      -cresol producer\n                      <jats:italic>Clostridioides difficile<\/jats:italic>\n                      in TW (Flight) vs. HR (Ground) for Post-flight, Inflight, and Overall (adj p = 0.014, adj p = 0.0006, and adj p = 2.02x10\u00af\n                      <jats:sup>5<\/jats:sup>\n                      , respectively). Concomitantly, we observed a significant increase in count-normalized abundance for another of the major\n                      <jats:italic>p<\/jats:italic>\n                      -cresol producers\n                      <jats:italic>Olsenella uli<\/jats:italic>\n                      in TW vs. HR for Post-flight, Inflight, and Overall (adj p = 0.0045, adj p = 0.00043, adj p = 0.0016, respectively), including Interaction for Inflight vs. Pre-flight (adj p = 0.028).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>\n                      We observed an elevation of\n                      <jats:italic>p<\/jats:italic>\n                      -cresol during one year in space, which may have significant implications for astronaut health and performance. Molecular findings and\n                      <jats:italic>p<\/jats:italic>\n                      -cresol countermeasure candidates are discussed. We also explore the process from untargeted molecular feature extraction to description of biological meaning, to new hypothesis generation, to plausible countermeasure development for human spaceflight.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1878680","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T10:40:41Z","timestamp":1790592041000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Systemic elevation of gut derived p-cresol during one year in space: implications for brain, heart, bone, liver and microbiome in astronauts"],"prefix":"10.3389","volume":"17","author":[{"given":"Michael A.","family":"Schmidt","sequence":"first","affiliation":[{"name":"Sovaris Aerospace","place":["Boulder, CO, United States"]},{"name":"Department of Medicine, Aerospace Medicine, University of Central Florida College of Medicine","place":["Orlando, FL, United States"]},{"name":"Center for Aerospace and Extreme Environments Medicine, UCF College of Medicine","place":["Orlando, FL, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caleb M.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Sovaris Aerospace","place":["Boulder, CO, United States"]},{"name":"Department of Systems Engineering, Colorado State University","place":["Fort Collins, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julian C.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Sovaris Aerospace","place":["Boulder, CO, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cem","family":"Meydan","sequence":"additional","affiliation":[{"name":"Division of Hematology and Medical Oncology, Sanford I. Weill Department of Medicine, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Evan E.","family":"Afshin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eliah G.","family":"Overbey","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"Center for STEM, University of Austin (UATX)","place":["Austin, TX, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"JangKeun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruth Subhash","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, Rensselaer Polytechnic Institute","place":["Troy, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Afshin","family":"Beheshti","sequence":"additional","affiliation":[{"name":"Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard","place":["Cambridge, MA, United States"]},{"name":"Center for Space Biomedicine, Trivedi Institute for Space and Global Biomedicine, University of Pittsburgh School of Medicine","place":["Pittsburgh, PA, United States"]},{"name":"McGowan Institute for Regenerative Medicine, Department of Surgery, University of Pittsburgh","place":["Pittsburgh, PA, United States"]},{"name":"Computational and Systems Biology, University of Pittsburgh School of Medicine","place":["Pittsburgh, PA, United States"]},{"name":"Trivedi Institute for Space and Global Biomedicine, University of Pittsburgh School of Medicine","place":["Pittsburgh, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher E.","family":"Mason","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"Computational and Systems Biology, University of Pittsburgh School of Medicine","place":["Pittsburgh, PA, United States"]},{"name":"Trivedi Institute for Space and Global Biomedicine, University of Pittsburgh School of Medicine","place":["Pittsburgh, PA, United States"]},{"name":"The WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medicine","place":["New York, NY, United States"]},{"name":"The Feil Family Brain and Mind Research Institute, Weill Cornell Medicine","place":["New York, NY, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fufo.2025.100680","article-title":"Recent advances in prebiotics: Classification, mechanisms, and health applications","volume":"12","author":"Ali","year":"2025","journal-title":"Future Foods."},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2023.117273","article-title":"A novel non-invasive colorectal cancer diagnostic method: Volatile organic compounds as biomarkers","volume":"542","author":"Alustiza","year":"2023","journal-title":"Clin. 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