Biology subjects

Corman, V.

Publications and source records attributed to Corman, V..

3 recordsLinked to original sources

bioRxiv2022

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

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, IFN{gamma} and/or TNF. Collectively, our study identifies correlated microbiome and metabolome alterations as a potential contributor to inflammatory dysregulation in severe COVID-19. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=150 HEIGHT=200 SRC="FIGDIR/small/518860v1_ufig1.gif" ALT="Figure 1"> View larger version (48K): org.highwire.dtl.DTLVardef@afc4edorg.highwire.dtl.DTLVardef@1a9ac2aorg.highwire.dtl.DTLVardef@65fb46org.highwire.dtl.DTLVardef@153ee6a_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2021

Transcriptomic responses of the human kidney to acute injury at single cell resolution

BackgroundAcute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood. MethodsWe performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Specimens were obtained within 1-2 hours after individuals had succumbed to critical illness associated with respiratory infections, with 4 of 8 individuals diagnosed with COVID-19. Control kidney tissues were obtained post-mortem or after nephrectomy from individuals without AKI. ResultsHigh-depth single cell-resolved gene expression data of human kidneys affected by AKI revealed enrichment of novel injury-associated cell states within the major cell types of the tubular epithelium, in particular in proximal tubules, thick ascending limbs and distal convoluted tubules. Four distinct, hierarchically interconnected injured cell states were distinguishable and characterized by transcriptome patterns associated with oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition, respectively. Transcriptome differences between individuals with AKI were driven primarily by the cell type-specific abundance of these four injury subtypes rather than by private molecular responses. AKI-associated changes in gene expression between individuals with and without COVID-19 were similar. ConclusionThe study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies.

molecular biology↗

bioRxiv2021

Evidence of MHC class I and II influencing viral and helminth infection via the microbiome in a non-human primate

Until recently, the study of major histocompability complex (MHC) mediated immunity has focused on the direct link between MHC variability and susceptibility to parasite infection. However, MHC genes can also influence host health indirectly through the sculpting of the bacterial community that in turn shape immune responses. We investigated the links between MHC class I and II gene variability gut microbiome diversity and micro- (adenovirus, AdV) and macro- (helminth) parasite infection probabilities in a wild population of non-human primates, mouse lemurs of Madagascar. This setup encompasses a plethora of underlying interactions between parasites, microbes and adaptive immunity in natural populations. Both MHC classes explained shifts in microbiome composition and the effect was driven by a few select microbial taxa. Among them were three taxa (Odoribacter, Campylobacter and Prevotellaceae-UCG-001) which were in turn linked to AdV and helminth infection status, evidence of the indirect effect of the MHC via the microbiome. Our study provides support for the coupled role of MHC variability and microbial flora as contributing factors of parasite infection. Author summaryThe selective pressure of the major histocompatibility complex (MHC) on microbial communities, and the potential role of this interaction in driving parasite resistance has been largely neglected. Using a natural population of the primate Microcebus griseorufus, we provide evidence of two outstanding findings: that MHCI and MHCII diversity shapes the composition of the gut microbiota; and that select taxa associated with MHC variability predicted adenovirus and helminth infection status. Our study highlights the importance of incorporating the microbiome when investigating parasite-mediated MHC selection.

evolutionary biology↗