Alteration of the Gut–Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study
Angela Horvath, Hansjörg Habisch, Barbara Prietl, Verena Pfeifer, Irina Balazs, Gabor Kovacs, Vasile Foris, Nikolaus John, Daniela Kleinschek, Nicole Feldbacher, Henning Grønbæk, Holger Jon Møller, Kristina Žukauskaitė, Tobias Madl, Vanessa Stadlbauer
Nutrients, doi:10.3390/nu16223840
Background: The gut-lung 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-lung 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-lung 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-lung axis after severe COVID-19 infection and suggests that probiotics can modulate the biomarkers of the gut-lung axis.
Author Contributions: Conceptualization, A.H. and V.S.; formal analysis, A.H. and I.B.; methodology, A.H.; visualization, A.H.; writing-original draft preparation, A.H. and V.S.; writing-review and editing, A.H., K.Ž. and V.S.; data curation, H.H., B.P., V.P., I.B., G.K., V.F., N.J., D.K., N.F., H.G., H.J.M. and T.M.; project administration, N.F. and K.Ž.; funding acquisition, V.S.; investigation, V.S.; supervision, V.S. All authors have read and agreed to the published version of the manuscript.
Institutional Review Board
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'abstract': '<jats:p>Background: The gut–lung 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–lung 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–lung 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–lung axis after severe COVID-19 '
'infection and suggests that probiotics can modulate the biomarkers of the gut–lung '
'axis.</jats:p>',
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