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The gut\u2013lung axis could be a potential therapeutic target for improving post-acute COVID-19 symptoms, and probiotics have been proposed as possible modulators. Aim: We conducted a pilot study to understand alterations in the gut\u2013lung axis and to explore the effects of a probiotic in post-acute COVID-19 disease. Methods: We included patients after severe COVID-19 disease (sCOV, n = 21) in a randomized, placebo-controlled trial to test the effect of a probiotic (Pro-Vi 5, Institute Allergosan, Graz, Austria) in a six-month intervention and used patients after mild disease (mCOV, n = 10) as controls, to compare the intestinal microbiome, metabolome, and patient-reported outcomes and biomarkers along the gut\u2013lung axis at baseline and throughout probiotic intervention. Results: Compared to mCOV patients, sCOV patients showed lower microbial richness, which was significantly improved by probiotic intervention. A reorganization of Ruminococcaceae and Lachnospiraceae taxa was observed in sCOV patients but remained unaffected by the intervention. Serum metabolome showed a dysregulation of lipoproteins in accordance with higher BMI and comorbidities in sCOV patients. HDL and LDL fractions\/components were temporarily decreased in the probiotic group. Stool metabolome was altered at baseline in sCOV patients and an increase in L-DOPA after 3 months and butyrate after 6 months of intervention could be observed. Probiotics partially improved reduced quality of life and modulated altered immune responses in sCOV patients. Increased intestinal permeability at baseline remained unaffected. Conclusion: The study provides evidence of long-term alterations of the gut\u2013lung axis after severe COVID-19 infection and suggests that probiotics can modulate the biomarkers of the gut\u2013lung axis.<\/jats:p>","DOI":"10.3390\/nu16223840","type":"journal-article","created":{"date-parts":[[2024,11,8]],"date-time":"2024-11-08T11:59:17Z","timestamp":1731067157000},"page":"3840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Alteration of the Gut\u2013Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study"],"prefix":"10.3390","volume":"16","author":[{"given":"Angela","family":"Horvath","sequence":"first","affiliation":[{"name":"Center for Biomarker Research in Medicine (CBmed), Division of Translational Precision Medicine, Division of Precision Medicine Technologies, 8010 Graz, Austria"},{"name":"Division for Gastroenterology and Hepatology, 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