Gut microbiome predicts atopic diseases in an infant cohort with reduced bacterial exposure due to social distancing (preprint)

Several hypotheses link altered microbial exposure in affluent societies to increased prevalence of allergies, but none have been experimentally tested in humans. Here we capitalize on the opportunity to study a cohort of infants (CORAL) raised during COVID-19 associated social distancing measures to test the interactions between bacterial exposure and fecal microbiome composition with atopic outcomes. We show that fecal Clostridia levels were significantly lower in CORAL infants and correlated with a microbial exposure index. Microbiota composition was the most significant component of regression models predicting risk of atopic dermatitis (AUC 0.86) or food allergen sensitization (AUC 0.98) and mediated the effects of multiple environment factors on disease risk. Although diet had a larger effect on microbiota composition than environmental factors linked to dispersal, most effects were mediated through the microbiota. This study provides critical information to refine existing hypothesis on the importance of the gut microbiota to immune development.

Excessive inflammatory and metabolic responses to acute SARS-CoV-2 infection are associated with a distinct gut microbiota composition (preprint)

Protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and associated clinical sequelae requires well-coordinated metabolic and immune responses that limit viral spread and promote recovery of damaged systems. In order to understand potential mechanisms and interactions that influence coronavirus disease 2019 (COVID-19) outcomes, we performed a multi-omics analysis on hospitalised COVID-19 patients and compared those with the most severe outcome (i.e. death) to those with severe non-fatal disease, or mild/moderate disease, that recovered. A distinct subset of 8 cytokines and 140 metabolites in sera identified those with a fatal outcome to infection. In addition, elevated levels of multiple pathobionts and lower levels of protective or anti-inflammatory microbes were observed in the faecal microbiome of those with the poorest clinical outcomes. Weighted gene correlation network analysis (WGCNA) identified modules that associated severity-associated cytokines with tryptophan metabolism, coagulation-linked fibrinopeptides, and bile acids with multiple pathobionts. In contrast, less severe clinical outcomes associated with clusters of anti-inflammatory microbes such as Bifidobacterium or Ruminococcus, short chain fatty acids (SCFAs) and IL-17A. Our study uncovered distinct mechanistic modules that link host and microbiome processes with fatal outcomes to SARS-CoV-2 infection. These features may be useful to identify at risk individuals, but also highlight a role for the microbiome in modifying hyperinflammatory responses to SARS-CoV-2 and other infectious agents.