BioProject

The gut microbiota plays a critical role in maintaining health, and its dysbiosis has been associated with several diseases, such as inflammatory bowel disease. More...

The gut microbiota plays a critical role in maintaining health, and its dysbiosis has been associated with several diseases, such as inflammatory bowel disease. The oxidative environment caused by chronic inflammation has been identified as an important factor driving disease-specific changes in microbiota composition. However, in vivo data are often confounded by high donor variability and the complex host environment. Furthermore, the tolerance of gut anaerobes to specific oxidants remains largely unexplored. This complexity underscores the need to study microbial oxidative stress responses under controlled in vitro conditions. To address this, we developed a cultivation-based model to study the oxidative stress tolerance of representative intestinal strains (n=41) and fecal-derived gut microbiota from healthy adults (n=7) in a high-throughput manner. We evaluated twelve different hydrogen peroxide (H2O2) and oxygen (O2) conditions each. Our experimental setup included successive passages to examine stress responses and recovery patterns. We comprehensively characterized a representative panel of 41 gut microbial species for the potential to grow and recover from H2O2 and O2 stress, providing important information about strain-specific tolerances relative to others. Our comparative assessment of pure strain tolerances confirmed the high sensitivity of Faecalibacterium spp. and the revealed high sensitivity of Fusicatenibacter saccharivorans and Lachnospira eligens to both H2O2 and O2. We also corroborate that several Bacteroides spp. exhibit uniquely high tolerance to both oxidants compared to the rest of the tested species. Furthermore, pure strain tolerances could explain the main taxonomic patterns in complex communities when exposed to selected oxidative stress modeling conditions, i.e., 0.71 mM H2O2 or aerobic incubation. These conditions induced biologically relevant oxidative stress-mediated dysbiosis in fecal-derived microbial communities, including the loss of sensitive anaerobes (e.g., butyrate-producers) and the bloom of facultative anaerobes (e.g., Enterococcus, Streptococcus, Escherichia-Shigella). The proposed H2O2 and O2 conditions can be used to rapidly screen biologically relevant oxidative stress responses in fecal cultures, with the potential to characterize donor-specific shifts in the community or metabolic activities. Less...