Multi-Strain Probiotic Intervention Modestly Modulates Microbial Composition and Inflammatory Profile in Individuals with Long COVID

DOI record: { "DOI": "10.3390/microorganisms14040734", "ISSN": [ "2076-2607" ], "URL": "http://dx.doi.org/10.3390/microorganisms14040734", "abstract": "<jats:p>Probiotics are widely used to support host health by modulating microbial communities and immune–metabolic homeostasis. Such interventions may be particularly relevant in long COVID syndrome, a condition characterized by persistent symptoms, low-grade inflammation, and microbiota alterations following SARS-CoV-2 infection. This study investigated the effects of a multi-strain probiotic on gut microbiota composition and predicted functional potential and biochemical parameters in individuals with long COVID and convalescent participants. Healthy individuals were included as reference controls. In an interventional study, 34 participants received a 12-week probiotic formulation containing Saccharomyces boulardii, Lacticaseibacillus rhamnosus GG, and two Lactiplantibacillus plantarum strains, while 40 served as non-supplemented controls. Fecal microbiota, assessed using 16S rRNA sequencing, and biochemical markers were measured at baseline and post-intervention. Probiotic supplementation induced selective compositional changes without significantly altering overall microbial diversity. Effects were more pronounced in long COVID participants and included enrichment of bacteria associated with metabolic and immune regulation, including Adlercreutzia, Coprococcus, and Eubacterium. Functional prediction analysis identified a probiotic-responsive signature in long-COVID-affected individuals, characterized by enrichment of pathways related to energy metabolism and redox balance. These microbial changes were accompanied by a consistent trend toward reduced inflammatory and hepatic markers. Overall, probiotic intervention demonstrated microbiota-status-dependent potential in long COVID recovery.</jats:p>", "alternative-id": [ "microorganisms14040734" ], "author": [ { "ORCID": "https://orcid.org/0000-0002-9615-1932", "affiliation": [ { "name": "Innovation Centre of Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia" } ], "authenticated-orcid": false, "family": "Bačić", "given": "Ana", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "first" }, { "ORCID": "https://orcid.org/0000-0003-4694-5416", "affiliation": [ { "name": "Department of Gastroenterology and Hepatology, Clinic for Internal Medicine, University Hospital Medical Center “Bežanijska Kosa”, 11000 Belgrade, Serbia" } ], "authenticated-orcid": false, "family": "Gmizić", "given": "Tijana", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0002-9676-7198", "affiliation": [ { "name": "Department of Gastroenterology and Hepatology, Clinic for Internal Medicine, University Hospital Medical Center “Bežanijska Kosa”, 11000 Belgrade, Serbia" }, { "name": "Faculty of Medicine, University of Belgrade, 11000 Belgrade, Serbia" } ], "authenticated-orcid": false, "family": "Branković", "given": "Marija", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" }, { "ORCID": "https://orcid.org/0000-0003-1624-1557", "affiliation": [ { "name": "Department of Biochemical Engineering and Biotechnology, Faculty of Technology and Metallurgy, University of Belgrade, 11000 Belgrade, Serbia" } ], "authenticated-orcid": false, "family": "Rajilić-Stojanović", "given": "Mirjana", "role": [ { "role": "author", "vocabulary": "crossref" } ], "sequence": "additional" } ], "container-title": "Microorganisms", "container-title-short": "Microorganisms", "content-domain": { "crossmark-restriction": false, "domain": [] }, "created": { "date-parts": [ [ 2026, 4, 7 ] ], "date-time": "2026-04-07T12:05:49Z", "timestamp": 1775563549000 }, "deposited": { "date-parts": [ [ 2026, 4, 8 ] ], "date-time": "2026-04-08T04:20:20Z", "timestamp": 1775622020000 }, "funder": [ { "DOI": "10.13039/501100004564", "award": [ "451-03-34/2026-03/200135" ], "award-info": [ { "award-number": [ "451-03-34/2026-03/200135" ] } ], "doi-asserted-by": "crossref", "id": [ { "asserted-by": "crossref", "id": "10.13039/501100004564", "id-type": "DOI" } ], "name": "Ministry of Education, Science and Technological Development of the Republic of Serbia" }, { "name": "AbelaPharm Probiotic Excellence Center" } ], "indexed": { "date-parts": [ [ 2026, 4, 8 ] ], "date-time": "2026-04-08T05:00:12Z", "timestamp": 1775624412186, "version": "3.50.1" }, "is-referenced-by-count": 0, "issue": "4", "issued": { "date-parts": [ [ 2026, 3, 25 ] ] }, "journal-issue": { "issue": "4", "published-online": { "date-parts": [ [ 2026, 4 ] ] } }, "language": "en", "license": [ { "URL": "https://creativecommons.org/licenses/by/4.0/", "content-version": "vor", "delay-in-days": 0, "start": { "date-parts": [ [ 2026, 3, 25 ] ], "date-time": "2026-03-25T00:00:00Z", "timestamp": 1774396800000 } } ], "link": [ { "URL": "https://www.mdpi.com/2076-2607/14/4/734/pdf", "content-type": "unspecified", "content-version": "vor", "intended-application": "similarity-checking" } ], "member": "1968", "original-title": [], "page": "734", "prefix": "10.3390", "published": { "date-parts": [ [ 2026, 3, 25 ] ] }, "published-online": { "date-parts": [ [ 2026, 3, 25 ] ] }, "publisher": "MDPI AG", "reference": [ { "DOI": "10.3389/fphar.2021.724033", "doi-asserted-by": "crossref", "key": "ref_1", "unstructured": "Cruz, C.S., Ricci, M.F., and Vieira, A.T. 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