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Alteration of the Gut–Lung Axis After Severe COVID-19 Infection and Modulation Through Probiotics: A Randomized, Controlled Pilot Study

Horvath et al., Nutrients, doi:10.3390/nu16223840, NCT04813718
Nov 2024  
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Probiotics for COVID-19
18th treatment shown to reduce risk in March 2021, now with p = 0.0000011 from 28 studies.
No treatment is 100% effective. Protocols combine treatments.
5,100+ studies for 112 treatments. c19early.org
Randomized controlled trial of 21 patients after severe COVID-19 infection showing improved microbial richness, stool metabolites, innate immune function, and quality of life with a multispecies probiotic compared to placebo over 6 months. The study also found persistent differences in the gut microbiome, metabolome, and immune parameters in patients after severe compared to mild COVID-19 infection at baseline, 7-10 months after infection.
Probiotic efficacy depends on the specific strains used. Specific microbes may decrease or increase COVID-19 risk1.
Horvath et al., 8 Nov 2024, Double Blind Randomized Controlled Trial, placebo-controlled, Austria, peer-reviewed, 15 authors, study period 2 June, 2021 - 17 July, 2022, trial NCT04813718 (history). Contact: vanessa.stadlbauer@medunigraz.at (corresponding author), angela.horvath@cbmed.at, barbara.prietl@cbmed.at, verena.pfeifer@cbmed.at, dr.irina.balazs@gmail.com, nicole.feldbacher@cbmed.at, kristina.zukauskaite@medunigraz.at, hansjoerg.habisch@medunigraz.at, tobias.madl@medunigraz.at, gabor.kovacs@uniklinikum.kages.at, vasile.foris@medunigraz.at, nikolaus.john@medunigraz.at, daniela.kleinschek@lvr.lbg.ac.at, henning.gronbaek@aarhus.rm.dk, holgmoel@rm.dk.
This PaperProbioticsAll
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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{ 'indexed': { 'date-parts': [[2024, 11, 9]], 'date-time': '2024-11-09T05:18:41Z', 'timestamp': 1731129521949, 'version': '3.28.0'}, 'reference-count': 110, 'publisher': 'MDPI AG', 'issue': '22', 'license': [ { 'start': { 'date-parts': [[2024, 11, 8]], 'date-time': '2024-11-08T00:00:00Z', 'timestamp': 1731024000000}, 'content-version': 'vor', 'delay-in-days': 0, 'URL': 'https://creativecommons.org/licenses/by/4.0/'}], 'content-domain': {'domain': [], 'crossmark-restriction': False}, '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>', 'DOI': '10.3390/nu16223840', 'type': 'journal-article', 'created': {'date-parts': [[2024, 11, 8]], 'date-time': '2024-11-08T16:59:17Z', 'timestamp': 1731085157000}, 'page': '3840', 'source': 'Crossref', 'is-referenced-by-count': 0, 'title': 'Alteration of the Gut–Lung 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, Department of ' 'Internal Medicine, Medical University of Graz, 8010 Graz, ' 'Austria'}]}, { 'ORCID': 'http://orcid.org/0000-0001-5537-506X', 'authenticated-orcid': False, 'given': 'Hansjörg', 'family': 'Habisch', 'sequence': 'additional', 'affiliation': [ { 'name': 'Otto Loewi Research Center, Medicinal Chemistry, Medical ' 'University of Graz, 8010 Graz, Austria'}, {'name': 'BioTechMed-Graz, 8010 Graz, Austria'}]}, { 'given': 'Barbara', 'family': 'Prietl', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center for Biomarker Research in Medicine (CBmed), Division of ' 'Translational Precision Medicine, Division of Precision Medicine ' 'Technologies, 8010 Graz, Austria'}, { 'name': 'Division of Endocrinology and Diabetes, Department of Internal ' 'Medicine, Medical University of Graz, 8010 Graz, Austria'}]}, { 'given': 'Verena', 'family': 'Pfeifer', 'sequence': 'additional', 'affiliation': [ { 'name': 'Center for Biomarker Research in Medicine (CBmed), Division of ' 'Translational Precision Medicine, Division of Precision Medicine ' 'Technologies, 8010 Graz, Austria'}, { 'name': 'Division of Endocrinology and Diabetes, Department of Internal ' 'Medicine, Medical University of Graz, 8010 Graz, Austria'}]}, { 'ORCID': 'http://orcid.org/0000-0003-2026-3521', 'authenticated-orcid': False, 'given': 'Irina', 'family': 'Balazs', 'sequence': 'additional', '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, Department of ' 'Internal Medicine, Medical University of Graz, 8010 Graz, ' 'Austria'}]}, { 'given': 'Gabor', 'family': 'Kovacs', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Pulmonology, Department of Internal Medicine, ' 'Medical University of Graz, 8010 Graz, Austria'}]}, { 'ORCID': 'http://orcid.org/0000-0002-8863-0298', 'authenticated-orcid': False, 'given': 'Vasile', 'family': 'Foris', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Pulmonology, Department of Internal Medicine, ' 'Medical University of Graz, 8010 Graz, Austria'}]}, { 'given': 'Nikolaus', 'family': 'John', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division of Pulmonology, Department of Internal Medicine, ' 'Medical University of Graz, 8010 Graz, Austria'}]}, { 'given': 'Daniela', 'family': 'Kleinschek', 'sequence': 'additional', 'affiliation': [ { 'name': 'Ludwig Boltzmann Institute for Lung Vascular Research, 8010 ' 'Graz, Austria'}]}, { 'given': 'Nicole', 'family': 'Feldbacher', 'sequence': 'additional', '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, Department of ' 'Internal Medicine, Medical University of Graz, 8010 Graz, ' 'Austria'}]}, { 'given': 'Henning', 'family': 'Grønbæk', 'sequence': 'additional', 'affiliation': [ { 'name': 'Departments of Hepatology and Gastroenterology, Aarhus ' 'University Hospital, 8200 Aarhus, Denmark'}, { 'name': 'Department of Clinical Medicine, Aarhus University, 8000 Aarhus, ' 'Denmark'}]}, { 'given': 'Holger Jon', 'family': 'Møller', 'sequence': 'additional', 'affiliation': [ { 'name': 'Department of Clinical Medicine, Aarhus University, 8000 Aarhus, ' 'Denmark'}, { 'name': 'Department of Clinical Biochemistry, Aarhus University Hospital, ' '8200 Aarhus, Denmark'}]}, { 'given': 'Kristina', 'family': 'Žukauskaitė', 'sequence': 'additional', 'affiliation': [ { 'name': 'Division for Gastroenterology and Hepatology, Department of ' 'Internal Medicine, Medical University of Graz, 8010 Graz, ' 'Austria'}, { 'name': 'Institute of Biosciences, Life Sciences Center, Vilnius ' 'University, 01513 Vilnius, Lithuania'}]}, { 'ORCID': 'http://orcid.org/0000-0002-9725-5231', 'authenticated-orcid': False, 'given': 'Tobias', 'family': 'Madl', 'sequence': 'additional', 'affiliation': [ { 'name': 'Otto Loewi Research Center, Medicinal Chemistry, Medical ' 'University of Graz, 8010 Graz, Austria'}, {'name': 'BioTechMed-Graz, 8010 Graz, Austria'}]}, { 'ORCID': 'http://orcid.org/0000-0001-5508-8271', 'authenticated-orcid': False, 'given': 'Vanessa', 'family': 'Stadlbauer', 'sequence': 'additional', '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, Department of ' 'Internal Medicine, Medical University of Graz, 8010 Graz, ' 'Austria'}, {'name': 'BioTechMed-Graz, 8010 Graz, Austria'}]}], 'member': '1968', 'published-online': {'date-parts': [[2024, 11, 8]]}, 'reference': [ { 'key': 'ref_1', 'doi-asserted-by': 'crossref', 'first-page': '603', 'DOI': 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Commun.'}], 'container-title': 'Nutrients', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.mdpi.com/2072-6643/16/22/3840/pdf', 'content-type': 'unspecified', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2024, 11, 8]], 'date-time': '2024-11-08T17:00:52Z', 'timestamp': 1731085252000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.mdpi.com/2072-6643/16/22/3840'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2024, 11, 8]]}, 'references-count': 110, 'journal-issue': {'issue': '22', 'published-online': {'date-parts': [[2024, 11]]}}, 'alternative-id': ['nu16223840'], 'URL': 'http://dx.doi.org/10.3390/nu16223840', 'relation': {}, 'ISSN': ['2072-6643'], 'subject': [], 'container-title-short': 'Nutrients', 'published': {'date-parts': [[2024, 11, 8]]}}
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