Salman A. Post-acute COVID-19 gastrointestinal sequelae: Mechanisms of persistent dysbiosis, intestinal barrier dysfunction, and emerging long-COVID phenotypes. World J Clin Infect Dis 2026; 15(1): 124175 [DOI: 10.5495/wjcid.124175]
Corresponding Author of This Article
Ahmed Salman, FRACP, FRCP, MRCP, Department of Internal Medicine, Kasr Alainy School of Medicine, 1 Al-Saray Street, Al-Manial, Cairo 11562, Egypt. awea844@gmail.com
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
review-article
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World J Clin Infect Dis. Sep 8, 2026; 15(1): 124175 Published online Sep 8, 2026. doi: 10.5495/wjcid.124175
Post-acute COVID-19 gastrointestinal sequelae: Mechanisms of persistent dysbiosis, intestinal barrier dysfunction, and emerging long-COVID phenotypes
Ahmed Salman
Ahmed Salman, Department of Internal Medicine, Kasr Alainy School of Medicine, Cairo 11562, Egypt
Author contributions: Salman A contributed to the study conception, manuscript drafting, critical revision, and final approval of the manuscript.
AI contribution statement: Claude (Anthropic) was used in a limited manner solely for language refinement, including grammar, clarity, and readability. All scientific content, interpretations, and conclusions were independently reviewed and verified by the authors, who take full responsibility for the integrity and accuracy of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Ahmed Salman, FRACP, FRCP, MRCP, Department of Internal Medicine, Kasr Alainy School of Medicine, 1 Al-Saray Street, Al-Manial, Cairo 11562, Egypt. awea844@gmail.com
Received: June 9, 2026 Revised: July 1, 2026 Accepted: July 14, 2026 Published online: September 8, 2026 Processing time: 91 Days and 5.3 Hours
Abstract
Post-acute coronavirus disease 2019 (COVID-19) syndrome (long COVID) affects 10%-30% of survivors and commonly presents with prolonged gastrointestinal symptoms, including chronic diarrhea, irritable bowel syndrome-like symptoms, and functional dyspepsia that may persist beyond 12 months. Gut dysbiosis-the depletion of short-chain fatty acid (SCFA)-producing commensals, such as Faecalibacterium prausnitzii and the enrichment of proinflammatory taxa, such as Ruminococcus gnavus-has been proposed as a central mechanism alongside intestinal barrier dysfunction, mucosal immune dysregulation, and persistent systemic inflammation. Severe acute respiratory syndrome coronavirus 2 infects intestinal epithelial cells via high ACE2 expression, with prolonged fecal shedding independent of respiratory clearance, potentially establishing dysbiosis that persists through SCFA depletion, reduced tryptophan metabolism, and barrier disruption, as reflected by elevated serum zonulin and I-FABP levels. These disturbances are associated with low-grade endotoxemia due to bacterial translocation and loss of immune tolerance, which may contribute to gastrointestinal and systemic manifestations via the gut-brain and gut-lung axes. Microbiota-targeted strategies, such as probiotics, synbiotics, and fecal microbiota transplantation, have shown preliminary benefits in early trials, although the evidence remains heterogeneous, and larger randomized trials are needed. This review synthesizes the current mechanistic insights, emerging biomarkers, and therapeutic implications to guide clinical management and future research.
Core Tip: Long-coronavirus disease gastrointestinal manifestations affect 10%-30% of survivors, but remain overlooked. Persistent dysbiosis-the loss of beneficial bacteria and pathogenic enrichment-drives symptoms through barrier dysfunction, immune dysregulation, and endotoxemia. Dysbiosis has been implicated as a potential contributor to short-chain fatty acid depletion and impaired tryptophan metabolism; however, current human evidence is largely observational, and causality remains unproven. Clinical biomarkers (zonulin, I-FABP, and dysbiotic signatures) enable patient stratification. Microbiota-targeted interventions (probiotics, synbiotics, fecal microbiota transplantation, and postbiotics) offer rational therapeutic approaches. This review establishes dysbiosis as a central therapeutic target and provides an evidence-based framework for its clinical management.
