Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines

The COVID-19 pandemic has highlighted the complex interplay between the gut microbiota and systemic immune responses, particularly through the gut–lung axis. Disruptions in gut microbial diversity and function—commonly referred to as dysbiosis—have been increasingly implicated in the pathogenesis of...

Full description

Saved in:
Bibliographic Details
Main Authors: Larissa S. Souza, Alexandre S. Ferreira-Junior, Pedro C. Estella, Ricardo K. Noda, Lhorena F. Sousa, Miguel T. Y. Murata, Lucas A. L. Carvalho, João L. Brisotti, Daniel G. Pinheiro, Josias Rodrigues, Carlos M. C. B. Fortaleza, Gislane L. V. de Oliveira
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Microorganisms
Subjects:
Online Access:https://www.mdpi.com/2076-2607/13/6/1407
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1849425699844128768
author Larissa S. Souza
Alexandre S. Ferreira-Junior
Pedro C. Estella
Ricardo K. Noda
Lhorena F. Sousa
Miguel T. Y. Murata
Lucas A. L. Carvalho
João L. Brisotti
Daniel G. Pinheiro
Josias Rodrigues
Carlos M. C. B. Fortaleza
Gislane L. V. de Oliveira
author_facet Larissa S. Souza
Alexandre S. Ferreira-Junior
Pedro C. Estella
Ricardo K. Noda
Lhorena F. Sousa
Miguel T. Y. Murata
Lucas A. L. Carvalho
João L. Brisotti
Daniel G. Pinheiro
Josias Rodrigues
Carlos M. C. B. Fortaleza
Gislane L. V. de Oliveira
author_sort Larissa S. Souza
collection DOAJ
description The COVID-19 pandemic has highlighted the complex interplay between the gut microbiota and systemic immune responses, particularly through the gut–lung axis. Disruptions in gut microbial diversity and function—commonly referred to as dysbiosis—have been increasingly implicated in the pathogenesis of SARS-CoV-2 infection. In this study, we assessed the gut bacteriome and permeability in SARS-CoV-2-infected patients using 16S sequencing and ELISA assays, respectively. We also measured blood inflammatory cytokines and fecal secretory IgA to evaluate systemic and mucosal immune responses. Significant alterations in both alpha and beta diversity metrics were observed in patients with COVID-19 (<i>n</i> = 79) and those with post-COVID-19 condition (<i>n</i> = 141) compared to the controls (<i>n</i> = 97). Differential abundance and taxonomic analyses revealed distinct microbial profiles in the infected groups. Increased plasma levels of IL-2, IL-6, IL-17A, IFN-γ, and zonulin were detected in patient samples. Some genera were elevated during acute infection, which was positively correlated with C-reactive protein, while <i>Enterobacteriaceae</i> and <i>Escherichia-Shigella</i> were associated with increased zonulin levels, indicating compromised intestinal barrier function. These findings suggest that gut dysbiosis may contribute to bacterial translocation and systemic inflammation. Overall, our results highlight the importance of the gut–lung axis and suggest that modulating the gut microbiota could support immune regulation in SARS-CoV-2 infection.
format Article
id doaj-art-9f2c5e991e3343fa904b9bc0b81058ac
institution Kabale University
issn 2076-2607
language English
publishDate 2025-06-01
publisher MDPI AG
record_format Article
series Microorganisms
spelling doaj-art-9f2c5e991e3343fa904b9bc0b81058ac2025-08-20T03:29:40ZengMDPI AGMicroorganisms2076-26072025-06-01136140710.3390/microorganisms13061407Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory CytokinesLarissa S. Souza0Alexandre S. Ferreira-Junior1Pedro C. Estella2Ricardo K. Noda3Lhorena F. Sousa4Miguel T. Y. Murata5Lucas A. L. Carvalho6João L. Brisotti7Daniel G. Pinheiro8Josias Rodrigues9Carlos M. C. B. Fortaleza10Gislane L. V. de Oliveira11Department of Genetics, Microbiology and Immunology, Institute of Biosciences (IBB), Sao Paulo State University (UNESP), Botucatu 18618-681, BrazilDepartment of Genetics, Microbiology and Immunology, Institute of Biosciences (IBB), Sao Paulo State University (UNESP), Botucatu 18618-681, BrazilBotucatu School of Medicine (FMB), Sao Paulo State University (UNESP), Botucatu 18618-687, BrazilBotucatu School of Medicine (FMB), Sao Paulo State University (UNESP), Botucatu 18618-687, BrazilSanta Casa Hospital, Ribeirão Preto 14085-000, BrazilSanta Casa Hospital, Ribeirão Preto 14085-000, BrazilDepartment of Agricultural, Livestock and Environmental Biotechnology, School of Agricultural and Veterinary Sciences (FCAV), Sao Paulo State University (UNESP), Jaboticabal 14884-900, BrazilSanta Casa Hospital, Ribeirão Preto 14085-000, BrazilDepartment of Agricultural, Livestock and Environmental Biotechnology, School of Agricultural and Veterinary Sciences (FCAV), Sao Paulo State University (UNESP), Jaboticabal 14884-900, BrazilDepartment of Genetics, Microbiology and Immunology, Institute of Biosciences (IBB), Sao Paulo State University (UNESP), Botucatu 18618-681, BrazilBotucatu School of Medicine (FMB), Sao Paulo State University (UNESP), Botucatu 18618-687, BrazilDepartment of Genetics, Microbiology and Immunology, Institute of Biosciences (IBB), Sao Paulo State University (UNESP), Botucatu 18618-681, BrazilThe COVID-19 pandemic has highlighted the complex interplay between the gut microbiota and systemic immune responses, particularly through the gut–lung axis. Disruptions in gut microbial diversity and function—commonly referred to as dysbiosis—have been increasingly implicated in the pathogenesis of SARS-CoV-2 infection. In this study, we assessed the gut bacteriome and permeability in SARS-CoV-2-infected patients using 16S sequencing and ELISA assays, respectively. We also measured blood inflammatory cytokines and fecal secretory IgA to evaluate systemic and mucosal immune responses. Significant alterations in both alpha and beta diversity metrics were observed in patients with COVID-19 (<i>n</i> = 79) and those with post-COVID-19 condition (<i>n</i> = 141) compared to the controls (<i>n</i> = 97). Differential abundance and taxonomic analyses revealed distinct microbial profiles in the infected groups. Increased plasma levels of IL-2, IL-6, IL-17A, IFN-γ, and zonulin were detected in patient samples. Some genera were elevated during acute infection, which was positively correlated with C-reactive protein, while <i>Enterobacteriaceae</i> and <i>Escherichia-Shigella</i> were associated with increased zonulin levels, indicating compromised intestinal barrier function. These findings suggest that gut dysbiosis may contribute to bacterial translocation and systemic inflammation. Overall, our results highlight the importance of the gut–lung axis and suggest that modulating the gut microbiota could support immune regulation in SARS-CoV-2 infection.https://www.mdpi.com/2076-2607/13/6/1407COVID-19post-COVID-19 conditiongut-lung axisbacteriome profileinflammatory cytokinesgut permeability
spellingShingle Larissa S. Souza
Alexandre S. Ferreira-Junior
Pedro C. Estella
Ricardo K. Noda
Lhorena F. Sousa
Miguel T. Y. Murata
Lucas A. L. Carvalho
João L. Brisotti
Daniel G. Pinheiro
Josias Rodrigues
Carlos M. C. B. Fortaleza
Gislane L. V. de Oliveira
Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
Microorganisms
COVID-19
post-COVID-19 condition
gut-lung axis
bacteriome profile
inflammatory cytokines
gut permeability
title Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
title_full Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
title_fullStr Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
title_full_unstemmed Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
title_short Bacteriome Signature in SARS-CoV-2-Infected Patients Correlates with Increased Gut Permeability and Systemic Inflammatory Cytokines
title_sort bacteriome signature in sars cov 2 infected patients correlates with increased gut permeability and systemic inflammatory cytokines
topic COVID-19
post-COVID-19 condition
gut-lung axis
bacteriome profile
inflammatory cytokines
gut permeability
url https://www.mdpi.com/2076-2607/13/6/1407
work_keys_str_mv AT larissassouza bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT alexandresferreirajunior bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT pedrocestella bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT ricardoknoda bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT lhorenafsousa bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT migueltymurata bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT lucasalcarvalho bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT joaolbrisotti bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT danielgpinheiro bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT josiasrodrigues bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT carlosmcbfortaleza bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines
AT gislanelvdeoliveira bacteriomesignatureinsarscov2infectedpatientscorrelateswithincreasedgutpermeabilityandsystemicinflammatorycytokines