{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T20:56:15Z","timestamp":1792788975462,"version":"4.5.0"},"reference-count":73,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Merit R&amp;D #BX004127"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>While there are many postulates for the etiology of post-viral chronic fatigue and other symptomatology, little is known. We draw on our past experience of these syndromes to devise means which can expose the primary players of this malady in terms of a panoply participating biomolecules and the state of the stool microbiome. Using databases established from a large dataset of patients at risk of colorectal cancer who were followed longitudinally over 3 decades, and a smaller database dedicated to building a Long PASC cohort (Post-Acute Sequelae of COVID-19), we were able to ascertain factors that predisposed patients to (and resulted in) significant changes in various biomarkers, i.e., the stool microbiome and serum cytokine levels, which we verified by collecting stool and serum samples. There were significant changes in the stool microbiome with an inversion from the usual Bacillota and Bacteroidota species. Serum cytokines showed significant differences in MIP-1\u03b2 versus TARC (CC chemokine ligand 17) in patients with either PASC or COVID-19 (p &lt; 0.02); IL10 versus IL-12p70a (p &lt; 0.02); IL-1b versus IL-6 (p &lt; 0.01); MCP1 versus TARC (p &lt; 0.03); IL-8 versus TARC (p &lt; 0.002); and Eotaxin3 versus TARC (p &lt; 0.004) in PASC. Some changes were seen solely in COVID-19, including MDC versus MIP-1\u03b1 (p &lt; 0.01); TNF-\u03b1 versus IL-1-\u03b2 (p &lt; 0.06); MCP4 versus TARC (p &lt; 0.0001). We also show correlates with chronic fatigue where an etiology was not identified. These findings in patients with positive criteria for PASC show profound changes in the microbiome and serum cytokine expression. Patients with chronic fatigue without clear viral etiologies also have common associations, including a history of tonsillectomy, which evokes a likely immune etiology.<\/jats:p>","DOI":"10.3390\/biom15070928","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T07:55:43Z","timestamp":1751442943000},"page":"928","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Immune Signatures in Post-Acute Sequelae of COVID-19 (PASC) and Myalgia\/Chronic Fatigue Syndrome (ME\/CFS): Insights from the Fecal Microbiome and Serum Cytokine Profiles"],"prefix":"10.3390","volume":"15","author":[{"given":"Martin","family":"Tobi","sequence":"first","affiliation":[{"name":"R&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9236-7683","authenticated-orcid":false,"given":"Diptaraj","family":"Chaudhari","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1577-0919","authenticated-orcid":false,"given":"Elizabeth P.","family":"Ryan","sequence":"additional","affiliation":[{"name":"Department of Environmental and Radiological Health Sciences,  School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5886-427X","authenticated-orcid":false,"given":"Noreen F.","family":"Rossi","sequence":"additional","affiliation":[{"name":"R&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USA"},{"name":"Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orena","family":"Koka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Wayne State University School of Medicine, Detroit, MI 48301, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bridget","family":"Baxter","sequence":"additional","affiliation":[{"name":"Department of Environmental and Radiological Health Sciences,  School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madison","family":"Tipton","sequence":"additional","affiliation":[{"name":"Department of Environmental and Radiological Health Sciences,  School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5101-1311","authenticated-orcid":false,"given":"Taru S.","family":"Dutt","sequence":"additional","affiliation":[{"name":"Department of Environmental and Radiological Health Sciences,  School of Health System, Public Health, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, Fort Collins, CO 80523, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0781-7681","authenticated-orcid":false,"given":"Yosef","family":"Tobi","sequence":"additional","affiliation":[{"name":"R&D Department, John D. Dingell VAMC, 4646 John R Street, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7876-149X","authenticated-orcid":false,"given":"Benita","family":"McVicker","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, University of Nebraska Medical Center, Omaha, NE 68005, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9749-1197","authenticated-orcid":false,"given":"Mariana","family":"Angoa-Perez","sequence":"additional","affiliation":[{"name":"R&D Department, John D. 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