{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T14:56:17Z","timestamp":1775832977903,"version":"3.50.1"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T00:00:00Z","timestamp":1775606400000},"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. Med."],"abstract":"<jats:p>Myalgic encephalomyelitis (ME)\/chronic fatigue syndrome (CFS) is a neuroimmune disease characterized by debilitating post-exertional malaise (PEM), brain-fog\/cognitive problems, and dysregulation of the autonomic nervous system. Currently, there are no objective biomarkers for ME\/CFS despite decades of research. Here, we compile evidence from literature that supports taste dysfunction, particularly alterations of taste perception mediated by Type II taste receptor cells, may be a critical underrecognized feature of ME\/CFS. The impetus is drawn from the emerging evidence of clinicopathological similarities between long-COVID and ME\/CFS. We discuss in parallel the mechanisms of cellular metabolism, inflammation, vascular dysfunction, and autonomic dysregulation in ME\/CFS and long-COVID pathophysiology. We postulate that mechanistically, dysregulation of ATP signaling through P2X2\/P2X3 purinergic receptors underlies both gustatory impairment and core ME\/CFS symptoms. Adopting information from the NIH-RECOVER shared resources, we present evidence that suggests chemosensory dysfunction as a potential indicator of progression\/severity of PEM. We discuss standardized taste testing as a non-invasive screening tool complementary to molecular biomarkers for ME\/CFS. Notwithstanding, we acknowledge the limitations, confounding and contributing factors such as medications and deficiencies that may exacerbate or independently cause taste-related symptoms in ME\/CFS. In conclusion, we present a compelling case for the multi-factorial role of taste dysfunction in ME\/CFS and suggest specific research priorities for investigating the relationship between chemosensory function and post-viral chronic illness.<\/jats:p>","DOI":"10.3389\/fmed.2026.1808646","type":"journal-article","created":{"date-parts":[[2026,4,8]],"date-time":"2026-04-08T05:33:04Z","timestamp":1775626384000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["A hypothesis connecting dysgeusia due to defects in ATP-P2X3 signaling and fatigue in myalgic encephalomyelitis\/chronic fatigue syndrome: lessons learned from long-COVID"],"prefix":"10.3389","volume":"13","author":[{"given":"Mythily","family":"Srinivasan","sequence":"first","affiliation":[{"name":"Department of Oral Pathology, Medicine and Radiology, Indiana University School of Dentistry","place":["Indianapolis, IN, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paule Valery","family":"Joseph","sequence":"additional","affiliation":[{"name":"National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health","place":["Bethesda, MD, United States"]},{"name":"National Smell and Taste Center, National Institute on Deafness and Other Communication Disorders, National Institutes of Health","place":["Bethesda, MD, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,8]]},"reference":[{"key":"ref1","volume-title":"Myalgic Encephalomyelitis (or Encephalopathy)\/Chronic Fatigue Syndrome: Diagnosis and Management","year":"2021"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"46","DOI":"10.7812\/TPP\/23.170","article-title":"Classification accuracy and description of myalgic encephalomyelitis\/chronic fatigue syndrome in an integrated health care system, 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