Ambient oxygen levels regulate intestinal dysbiosis and GVHD severity after allogeneic stem cell transplantation.

The severity of T cell-mediated gastrointestinal (GI) diseases such as graft-versus-host disease (GVHD) and inflammatory bowel diseases correlates with a decrease in the diversity of the host gut microbiome composition characterized by loss of obligate anaerobic commensals. The mechanisms underpinning these changes in the microbial structure remain unknown. Here, we show in multiple specific pathogen-free (SPF), gnotobiotic, and germ-free murine models of GI GVHD that the initiation of the intestinal damage by the pathogenic T cells altered ambient oxygen levels in the GI tract and caused dysbiosis. The change in oxygen levels contributed to the severity of intestinal pathology in a host intestinal HIF-1α- and a microbiome-dependent manner. Regulation of intestinal ambient oxygen levels with oral iron chelation mitigated dysbiosis and reduced the severity of the GI GVHD. Thus, targeting ambient intestinal oxygen levels may represent a novel, non-immunosuppressive strategy to mitigate T cell-driven intestinal diseases.

Lung and gut microbiota are altered by hyperoxia and contribute to oxygen-induced lung injury in mice.

Inhaled oxygen, although commonly administered to patients with respiratory disease, causes severe lung injury in animals and is associated with poor clinical outcomes in humans. The relationship between hyperoxia, lung and gut microbiota, and lung injury is unknown. Here, we show that hyperoxia conferred a selective relative growth advantage on oxygen-tolerant respiratory microbial species (e.g., Staphylococcus aureus) as demonstrated by an observational study of critically ill patients receiving mechanical ventilation and experiments using neonatal and adult mouse models. During exposure of mice to hyperoxia, both lung and gut bacterial communities were altered, and these communities contributed to oxygen-induced lung injury. Disruption of lung and gut microbiota preceded lung injury, and variation in microbial communities correlated with variation in lung inflammation. Germ-free mice were protected from oxygen-induced lung injury, and systemic antibiotic treatment selectively modulated the severity of oxygen-induced lung injury in conventionally housed animals. These results suggest that inhaled oxygen may alter lung and gut microbial communities and that these communities could contribute to lung injury.

The modulating role of dissolved organic matter on spatial patterns of microbial metabolism in Lake Erie sediments.

To evaluate the role of dissolved organic matter (DOM) on microbial community metabolism, we established extracellular enzyme activity (EEA) and substrate-induced respiration (SIR) profiles of sediment samples collected from littoral and profundal regions of the western, central, and eastern basins of Lake Erie. Lake Erie is spatially structured such that the central and western basins receive relatively major inputs of allochthonous DOM in comparison to the eastern basin. Overall, spatial patterns of EEA and SIR profiles suggest both greater metabolic diversity and activity in the littoral regions of the central and western basins. In contrast, the eastern basin demonstrated much less structuring between littoral and profundal areas. To evaluate whether the observed spatial patterns are the result of microbial community adaptations to local DOM availability, we performed three experimental treatments by inoculating sediment samples with polyvinylpyrrolidone, which sequesters large polyphenols, or with either vanillin or catechol, two small phenolic compounds. Our results revealed that esterase and glycosidase EEA from the eastern basin were induced by small phenolics and inhibited by large polyphenols. In contrast, the addition of small phenolics decreased esterase and glycosidase activities from the central basin, while polyphenols had a negligible effect. These results suggest that the source and composition of DOM play a significant role in the local adaptation of microbial communities, determining large-scale spatial patterns of microbial functional diversity in Lake Erie sediments.