Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications

Nagata, Naoyoshi; Takeuchi, Tadashi; Masuoka, Hiroaki; Aoki, Ryo; Ishikane, Masahiro; Iwamoto, Noriko; Sugiyama, Masaya; Suda, Wataru; Nakanishi, Yumiko; Terada-Hirashima, Junko; Kimura, Moto; Nishijima, Toshitaka; Inooka, Hiroshi; Miyoshi‐Akiyama, Tohru; Kojima, Yasushi; Shimokawa, Chikako; Hisaeda, Hajime; Zhang, Fen; Yeoh, Yun Kit; Ng, Siew C.; Uemura, Naomi; Itoi, Takao; Mizokami, Masashi; Kawai, Takashi; Sugiyama, Haruhito; Ohmagari, Norio; Ohno, Hiroshi

doi:10.1053/j.gastro.2022.09.024

Cited by 75 publications

(60 citation statements)

References 35 publications

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“…These include changes in diversity [39] including stark enrichments and/or loss of specific taxa [40]. Several Studies have focused on differences in the gut microbiome between patients with severe COVID-19 and controls [7,41,42]. Though these findings are essential, the effect on the larger population, wherein the infection is asymptomatic-to-moderate, is not readily represented.…”

Section: Discussionmentioning

confidence: 99%

“…For the data preprocessing, raw metagenomic reads were first trimmed to the maximal read length of 150 bases using Cutadapt (v3.4) [40]. The preprocessed metagenomic and raw metatranscriptomic reads were processed using IMP: reads were trimmed using Trimmomatic (v.39) [41], reads mapping to the human genome (hg38 genome) or PhiX genome (gi|9626372|ref|NC_001422.1, Enterobacteria phage phiX174 sensu lato, complete genome) were removed using BWA (v. 0.7.9a) [42], and the metatranscriptomic reads were further filtered using SortMeRNA (v.4.2.0-238-g90cdf6c) [43]. In addition, alpha-diversity estimation was performed from metagenomic reads using Nonpareil (v. 3.4.1) [44] as part of the IMP preprocessing step.…”

Section: Supplementary Materialsmentioning

confidence: 99%

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Altered infective competence of the human gut microbiome in COVID-19

Nies

Galata

Martin-Gallausiaux

et al. 2022

Preprint

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Objectives: Infections with SARS-CoV-2 have a pronounced impact on the gastrointestinal tract and its resident microbiome. Clear differences between severe cases of infection and healthy individuals have been reported, including the loss of commensal taxa. We aimed to understand if microbiome alterations including functional shifts are unique to severe cases or a common effect of COVID-19. Design: We used high-resolution systematic multi-omic analyses to profile the gut microbiome in asymptomatic-to-moderate COVID-19 individuals compared to a control group. Results: We found a striking increase in the overall abundance and expression of both virulence factors and antimicrobial resistance genes in COVID-19. Importantly, these genes are encoded and expressed by commensal taxa from families such as Acidaminococcaceae and Erysipelatoclostridiaceae, which we found to be enriched in COVID-19 positive individuals. We also found an enrichment in the expression of a betaherpesvirus and rotavirus C genes in COVID-19 positive individuals compared to healthy controls. Conclusion: Our analyses identified an altered and increased infective competence of the gut microbiome in COVID-19 patients.

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Section: Discussionmentioning

confidence: 99%

Section: Supplementary Materialsmentioning

confidence: 99%

Altered infective competence of the human gut microbiome in COVID-19

Nies

Galata

Martin-Gallausiaux

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…While several excellent microbiomics 20,24,27,44,45 , metabolomics 33 , and multi-omics studies 34,41,[46][47][48][49][50] of COVID-19 have been published, our work is unique in simultaneously measuring and analyzing a particularly large number of different -omics types, and, in this, the first to integrate gut and oropharyngeal metagenome sequencing, metabolomics, host transcriptomics, and cytokine profiling. Our analyses using linear mixed-effect models and exhaustive confounder testing revealed the plasma metabolome to be the -omics domain most affected by SARS-CoV-2 infection.…”

Section: Discussionmentioning

confidence: 99%

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

Essex

Pascual-Leone

Löber

et al. 2022

Preprint

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The clinical course of the 2019 coronavirus disease (COVID-19) is variable and to a substantial degree still unpredictable, especially in persons who have neither been vaccinated nor recovered from previous infection. We hypothesized that disease progression and inflammatory responses were associated with alterations in the microbiome and metabolome. To test this, we integrated metagenome, metabolome, cytokine, and transcriptome profiles of longitudinally collected samples from hospitalized COVID-19 patients at the beginning of the pandemic (before vaccines or variants of concern) and non-infected controls, and leveraged detailed clinical information and post-hoc confounder analysis to identify robust within- and cross-omics associations. Severe COVID-19 was directly associated with a depletion of potentially beneficial intestinal microbes mainly belonging to Clostridiales, whereas oropharyngeal microbiota disturbance appeared to be mainly driven by antibiotic use. COVID-19 severity was also associated with enhanced plasma concentrations of kynurenine, and reduced levels of various other tryptophan metabolites, lysophosphatidylcholines, and secondary bile acids. Decreased abundance of Clostridiales potentially mediated the observed reduction in 5-hydroxytryptophan levels. Moreover, altered plasma levels of various tryptophan metabolites and lower abundances of Clostridiales explained significant increases in the production of IL-6, IFNγ and/or TNFα. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19.

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“…Several studies reported that changes in the serum levels of maltose, mannose, succinic acid, and erythronic acid are associated with changes in gastrointestinal microbiome [46][47][48][49][50]. Moreover, a recent multi-omics study showed multiple gut microbe-metabolite-cytokine interrelationships in COVID-19 [51]. Of note is that changes in the microbiome have been associated with alterations in the levels of pentose glucuronate interconversion metabolites [52][53][54].…”

Section: Figurementioning

confidence: 99%

Combining Semi-targeted Metabolomics and Machine Learning to Identify Metabolic Alterations in Serum and Urine of Hospitalized Patients with COVID-19

Baiges-Gayà¹,

Iftimie²,

Castañé³

et al. 2022

Preprint

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Viral infections cause metabolic dysregulation in the infected organism. The present study used metabolomics techniques and machine learning algorithms to retrospectively analyze the alter-ations of a broad panel of metabolites in the serum and urine of a cohort of 126 patients hospi-talized with COVID-19. Results were compared with those of 50 healthy subjects and 45 COVID-19 negative patients but with bacterial infectious diseases. Metabolites were analyzed by gas chro-matography coupled to quadrupole time-of-flight mass spectrometry. The main metabolites al-tered in the sera of COVID-19 patients were those of pentose glucuronate interconversion, ascorbate and fructose metabolism, nucleotide sugars, and nucleotide and amino acid metabolism. Alterations in serum maltose, mannonic acid, xylitol, or glyceric acid metabolites segregated positive patients from the control group with high diagnostic accuracy, while succinic acid seg-regated positive patients from those with other disparate infectious diseases. Increased lauric acid concentrations were associated with severity of infection and death. Urine analyses could not discriminate between groups. Targeted metabolomics and machine learning algorithms facilitated the exploration of the metabolic alterations underlying COVID-19 infection, and to identify po-tential biomarkers for the diagnosis and prognosis of the disease.

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Human Gut Microbiota and Its Metabolites Impact Immune Responses in COVID-19 and Its Complications

Cited by 75 publications

References 35 publications

Altered infective competence of the human gut microbiome in COVID-19

Altered infective competence of the human gut microbiome in COVID-19

Gut microbiota dysbiosis is associated with altered tryptophan metabolism and dysregulated inflammatory response in severe COVID-19

Combining Semi-targeted Metabolomics and Machine Learning to Identify Metabolic Alterations in Serum and Urine of Hospitalized Patients with COVID-19

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