Hospitalised children with COVID-19 display an aberrant intestinal microbiota and a shift in faecal compounds related with the metabolism of vitamins and lipids
Miriam Sanz, Isabel Gutiérrez-Díaz, Hector González, Marta Velasco Rodríguez-Belvís, Rosaura Picáns-Leis, Santiago Jiménez, David González, Jorge Rodríguez, Macarena Queralt, Marta Herrador, Rafael Martín-Masot, Pablo Ferrer, Víctor M Navas-López, Beatriz Espín, Rosaura Leis, Juan J Díaz, Susana Delgado
PLOS One, doi:10.1371/journal.pone.0323910
The SARS-CoV-2 virus and its rapid spread have made it a global health concern. The aim of this was to investigate the microbial and metabolic faecal profiles of paediatric patients hospitalised for COVID-19 to try to identify biomarkers of predisposition to severity. The study included 16 patients (aged 4-14 years old) from six different Spanish hospitals and 20 age-matched healthy controls. The gut microbiota was characterised by sequencing of 16S rDNA amplicons and internal transcribed space amplicons, while the metabolic profile was analysed by liquid chromatography high resolution mass spectrometry. A different microbial profile was observed between patients and controls, with a significantly higher abundance of sequences belonging to the phyla Bacteroidota and Pseudomonadota in patients. A different metabolic profile was observed between the two groups. Non-infected children had higher faecal levels of vitamins such as niacin, thiamine, and vitamin D3 derivatives, which were negatively correlated with the abundance of pathogenic bacteria, such as members of Enterobacteriaceae. Hospitalisation due to SARS-CoV-2 infection in children was associated with changes in the gut microbiota and an altered metabolomic profile. For the first time, several relevant biological compounds were found to be reduced in the faeces of children hospitalised with COVID-19 compared to healthy controls. (SAMN40261256-SAMN40261291). Metabolic
Supporting information S1 File. S1 Writing -original draft: Isabel Gutiérrez-Diaz. Writing -review & editing: Susana Delgado, Hector González, Juan J. Díaz.
References
Bohn, Yousef, Steele, Sepiashvili, Adeli, MultiInflammatory Syndrome in Children: A View into Immune Pathogenesis from a Laboratory Perspective, J Appl Lab Med,
doi:10.1093/jalm/jfab114Cariolou, Cupp, Evangelou, Tzoulaki, Berlanga-Taylor, Importance of vitamin D in acute and critically ill children with subgroup analyses of sepsis and respiratory tract infections: a systematic review and meta-analysis, BMJ Open,
doi:10.1136/bmjopen-2018-027666Chatterjee, Lu, Zhang, Zhang, Dai et al., Vitamin D receptor promotes healthy microbial metabolites and microbiome, Sci Rep,
doi:10.1038/s41598-020-64226-7Costea, Zeller, Sunagawa, Pelletier, Alberti et al., Towards standards for human fecal sample processing in metagenomic studies, Nat Biotechnol,
doi:10.1038/nbt.3960Doenhardt, Hufnagel, Diffloth, Hübner, Mauer et al., Epidemiology of 7375 children and adolescents hospitalized with COVID-19 in Germany, reported via a prospective, nationwide surveillance study in 2020-2022, Sci Rep,
doi:10.1038/s41598-023-49210-1Farsi, Tahvildari, Arbabi, Vazife, Sechi et al., Diagnostic, Prognostic, and Therapeutic Roles of Gut Microbiota in COVID-19: A Comprehensive Systematic Review, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2022.804644Fu, Du, Chen, Shama, Chen et al., Exploring the impact of gut microbial metabolites on inactivated SARS-CoV-2 vaccine efficacy during pregnancy and mother-to-infant antibody transfer, Gut,
doi:10.1136/gutjnl-2023-330497Ghazanfar, Kandhi, Shin, Muthumanickam, Gurjar et al., Impact of COVID-19 on the Gastrointestinal Tract: A Clinical Review, Cureus,
doi:10.7759/cureus.23333Giacomet, Barcellini, Stracuzzi, Longoni, Folgori et al., Gastrointestinal Symptoms in Severe COVID-19 Children, Pediatr Infect Dis J,
doi:10.1097/INF.0000000000002843Guloyan, Oganesian, Baghdasaryan, Yeh, Singh et al., Glutathione Supplementation as an Adjunctive Therapy in COVID-19, Antioxidants,
doi:10.3390/antiox9100914Guo, Tao, Flavell, Zhu, Potential intestinal infection and faecal-oral transmission of SARS-CoV-2, Nat Rev Gastroenterol Hepatol,
doi:10.1038/s41575-021-00416-6Gutiérrez-Díaz, Sanz-Martinez, Castro, Rodríguez-Belvís, Carreira et al., Microbial and immune faecal determinants in infants hospitalized with COVID-19 reflect bifidobacterial dysbiosis and immature intestinal immunity, Eur J Pediatr,
doi:10.1007/s00431-023-05140-8Harris, Taylor, Thielke, Payne, Gonzalez et al., Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support, J Biomed Inform,
doi:10.1016/j.jbi.2008.08.010Hoque, Akter, Mishu, Islam, Rahman et al., Microbial co-infections in COVID-19: Associated microbiota and underlying mechanisms of pathogenesis, Microb Pathog,
doi:10.1016/j.micpath.2021.104941Hoque, Sarkar, Rahman, Akter, Banu et al., SARS-CoV-2 infection reduces human nasopharyngeal commensal microbiome with inclusion of pathobionts, Sci Rep,
doi:10.1038/s41598-021-03245-4Islam, Foysal, Hoque, Mehedi, Rob et al., Dysbiosis of Oral and Gut Microbiomes in SARS-CoV-2 Infected Patients in Bangladesh: Elucidating the Role of Opportunistic Gut Microbes, Front Med,
doi:10.3389/fmed.2022.821777Jimenez, Velasco Rodríguez-Belvís, Gonzalez, Ortega, Segarra et al., COVID-19 Gastrointestinal Manifestations Are Independent Predictors of PICU Admission in Hospitalized Pediatric Patients, Pediatr Infect Dis J,
doi:10.1097/INF.0000000000002935Larkin, Lassetter, Vitamin D deficiency and acute lower respiratory infections in children younger than 5 years: identification and treatment, J Pediatr Health Care,
doi:10.1016/j.pedhc.2014.08.013Milani, Hevia, Foroni, Duranti, Turroni et al., Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based analysis protocol, PLoS One,
doi:10.1371/journal.pone.0068739Milani, Lugli, Turroni, Mancabelli, Duranti et al., Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol, FEMS Microbiol Ecol,
doi:10.1111/1574-6941.12410Mizutani, Ishizaka, Koga, Ikeuchi, Saito et al., Correlation Analysis between Gut Microbiota Alterations and the Cytokine Response in Patients with Coronavirus Disease during Hospitalization, Microbiol Spectr,
doi:10.1128/spectrum.01689-21Pandit, Frishman, Multisystem Inflammatory Syndrome in Children during the COVID-19 Pandemic: A Review of Clinical Manifestations, Cardiac Complications and Medical Management, Cardiol Rev,
doi:10.1097/CRD.0000000000000565Park, Hosomi, Kawashima, Chen, Mohsen et al., Dietary Vitamin B1 Intake Influences Gut Microbial Community and the Consequent Production of Short-Chain Fatty Acids, Nutrients,
doi:10.3390/nu14102078Paysan-Lafosse, Blum, Chuguransky, Grego, Pinto et al., InterPro in 2022, Nucleic Acids Res,
doi:10.1093/nar/gkac993Petkova, Mineva, Botsova, Clinical Study of Vitamin D Levels in Hospitalized Children with Acute Respiratory Infections, Pediatr Rep,
doi:10.3390/pediatric16040088Petrelli, Oldani, Borgonovo, Cabiddu, Dognini et al., Vitamin D3 and COVID-19 Outcomes: An Umbrella Review of Systematic Reviews and Meta-Analyses, Antioxidants,
doi:10.3390/antiox12020247Romani, Chierico, Macari, Pane, Ristori et al., The Relationship Between Pediatric Gut Microbiota and SARS-CoV-2 Infection, Front Cell Infect Microbiol,
doi:10.3389/fcimb.2022.908492Smith, Johnson, Koshy, Hess, Qureshi et al., Thiamine deficiency disorders: a clinical perspective, Ann N Y Acad Sci,
doi:10.1111/nyas.14536Soto-Martin, Warnke, Farquharson, Christodoulou, Horgan et al., Vitamin Biosynthesis by Human Gut Butyrate-Producing Bacteria and Cross-Feeding in Synthetic Microbial Communities, mBio,
doi:10.1128/mBio.00886-20Stutz, Dylla, Pearson, Lecompte-Osorio, Nayak et al., Immunomodulatory fecal metabolites are associated with mortality in COVID-19 patients with respiratory failure, Nat Commun,
doi:10.1038/s41467-022-34260-2Su, Zhang, Qi, Gao, Yang et al., Gut microbiota-derived metabolite 3-idoleacetic acid together with LPS induces IL-35+ B cell generation, Microbiome,
doi:10.1186/s40168-021-01205-8Sud, Fahy, Cotter, Brown, Dennis et al., LMSD: LIPID MAPS structure database, Nucleic Acids Res,
doi:10.1093/nar/gkl838Suskun, Kilic, Ciftdogan, Guven, Karbuz et al., Intestinal microbiota composition of children with infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and multisystem inflammatory syndrome (MIS-C), Eur J Pediatr,
doi:10.1007/s00431-022-04494-9Valentino, Esposito, Colosimo, Caprio, Puzone et al., Gut microbiota and COVID-19: An intriguing pediatric perspective, World J Clin Cases,
doi:10.12998/wjcc.v10.i23.8076Wang, Bryant, Cheng, Wang, Gindulyte et al., PubChem BioAssay: 2017 update, Nucleic Acids Res,
doi:10.1093/nar/gkw1118Wang, Li, Wei, Lian, Sun et al., Respiratory influenza virus infection induces intestinal immune injury via microbiota-mediated Th17 cell-dependent inflammation, J Exp Med,
doi:10.1084/jem.20140625Wang, Zhou, Lu, Hu, Xiao et al., Altered gut microbiota composition in children and their caregivers infected with the SARS-CoV-2 Omicron variant, World J Pediatr,
doi:10.1007/s12519-022-00659-6Wishart, Guo, Oler, Wang, Anjum et al., HMDB 5.0: the Human Metabolome Database for 2022, Nucleic Acids Res,
doi:10.1093/nar/gkab1062Wishart, Oler, Peters, Guo, Girod et al., MiMeDB: the Human Microbial Metabolome Database, Nucleic Acids Res,
doi:10.1093/nar/gkac868Wu, Cheng, Jiang, Tang, Ming et al., Altered oral and gut microbiota and its association with SARS-CoV-2 viral load in COVID-19 patients during hospitalization, NPJ Biofilms Microbiomes,
doi:10.1038/s41522-021-00232-5Yao, Devotta, Li, Lunjani, Sadlier et al., Dysrupted microbial tryptophan metabolism associates with SARS-CoV-2 acute inflammatory responses and long COVID, Gut Microbes,
doi:10.1080/19490976.2024.2429754Yin, Minacapelli, Parmar, Catalano, Bhurwal et al., Alterations of the fecal microbiota in relation to acute COVID-19 infection and recovery, Mol Biomed,
doi:10.1186/s43556-022-00103-1Zhang, Lau, Liu, Su, Chan et al., Gut microbiota in COVID-19: key microbial changes, potential mechanisms and clinical applications, Nat Rev Gastroenterol Hepatol,
doi:10.1038/s41575-022-00698-4DOI record:
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"first-page": "478",
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"year": "2023"
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"DOI": "10.12998/wjcc.v10.i23.8076",
"article-title": "Gut microbiota and COVID-19: An intriguing pediatric perspective",
"author": "MS Valentino",
"doi-asserted-by": "crossref",
"first-page": "8076",
"issue": "23",
"journal-title": "World J Clin Cases",
"key": "pone.0323910.ref017",
"volume": "10",
"year": "2022"
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"DOI": "10.1016/B978-0-08-102723-3.00020-2",
"article-title": "Metabolomics",
"author": "S Nambiar",
"doi-asserted-by": "crossref",
"first-page": "758",
"key": "pone.0323910.ref018",
"volume-title": "Encyclopedia of Respiratory Medicine",
"year": "2022"
},
{
"DOI": "10.1016/j.compbiomed.2023.107661",
"article-title": "MetaboliteCOVID: A manually curated database of metabolite markers for COVID-19",
"author": "L Ren",
"doi-asserted-by": "crossref",
"first-page": "107661",
"journal-title": "Comput Biol Med",
"key": "pone.0323910.ref019",
"volume": "167",
"year": "2023"
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{
"DOI": "10.1016/j.jbi.2008.08.010",
"article-title": "Research electronic data capture (REDCap)--a metadata-driven methodology and workflow process for providing translational research informatics support",
"author": "PA Harris",
"doi-asserted-by": "crossref",
"first-page": "377",
"issue": "2",
"journal-title": "J Biomed Inform",
"key": "pone.0323910.ref020",
"volume": "42",
"year": "2009"
},
{
"DOI": "10.1038/nbt.3960",
"article-title": "Towards standards for human fecal sample processing in metagenomic studies",
"author": "PI Costea",
"doi-asserted-by": "crossref",
"first-page": "1069",
"issue": "11",
"journal-title": "Nat Biotechnol",
"key": "pone.0323910.ref021",
"volume": "35",
"year": "2017"
},
{
"DOI": "10.1371/journal.pone.0068739",
"article-title": "Assessing the fecal microbiota: an optimized ion torrent 16S rRNA gene-based analysis protocol",
"author": "C Milani",
"doi-asserted-by": "crossref",
"issue": "7",
"journal-title": "PLoS One",
"key": "pone.0323910.ref022",
"volume": "8",
"year": "2013"
},
{
"article-title": "Evaluation of bifidobacterial community composition in the human gut by means of a targeted amplicon sequencing (ITS) protocol",
"author": "C Milani",
"first-page": "493",
"issue": "2",
"journal-title": "FEMS Microbiol Ecol",
"key": "pone.0323910.ref023",
"volume": "90",
"year": "2014"
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"author": "Y Wang",
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"key": "pone.0323910.ref026",
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"first-page": "221",
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"DOI": "10.3389/fcimb.2022.804644",
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"first-page": "2397",
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"key": "pone.0323910.ref049",
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"article-title": "Importance of Vitamin D3 in COVID-19 Patients",
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"first-page": "1545",
"issue": "5",
"journal-title": "Arch Razi Inst",
"key": "pone.0323910.ref051",
"volume": "76",
"year": "2021"
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"DOI": "10.3390/antiox12020247",
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"first-page": "914",
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"DOI": "10.1186/s40168-021-01205-8",
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