Distinct Polysaccharide Utilization Determines Interspecies Competition between Intestinal Prevotella spp.

Prevotella spp. are a dominant bacterial genus within the human gut. Multiple Prevotella spp.

Variations in microbiota composition of laboratory mice influence Citrobacter rodentium infection via variable short-chain fatty acid production.

The composition of the intestinal microbiota influences the outcome of enteric infections in human and mice. However, the role of specific members and their metabolites contributing to disease severity is largely unknown. Using isogenic mouse lines harboring distinct microbiota communities, we observed highly variable disease kinetics of enteric Citrobacter rodentium colonization after infection.

Loss of CNFY toxin-induced inflammation drives Yersinia pseudotuberculosis into persistency.

Gastrointestinal infections caused by enteric yersiniae can become persistent and complicated by relapsing enteritis and severe autoimmune disorders. To establish a persistent infection, the bacteria have to cope with hostile surroundings when they transmigrate through the intestinal epithelium and colonize underlying gut-associated lymphatic tissues. How the bacteria gain a foothold in the face of host immune responses is poorly understood.

Enhancement of IFNγ Production by Distinct Commensals Ameliorates Salmonella-Induced Disease.

The microbiota contributes to colonization resistance against invading pathogens by competing for metabolites, producing inhibitory substances, and priming protective immune responses. However, the specific commensal bacteria that promote host resistance and immune-mediated protection remain largely elusive. Using isogenic mouse lines with distinct microbiota profiles, we demonstrate that severity of disease induced by enteric Salmonella Typhimurium infection is strongly modulated by microbiota composition in individual lines.

Microbiota Normalization Reveals that Canonical Caspase-1 Activation Exacerbates Chemically Induced Intestinal Inflammation.

Inflammasomes play a central role in regulating intestinal barrier function and immunity during steady state and disease. Because the discoveries of a passenger mutation and a colitogenic microbiota in the widely used caspase-1-deficient mouse strain have cast doubt on previously identified direct functions of caspase-1, we reassessed the role of caspase-1 in the intestine. To this end, we generated Casp1 and Casp11 mice and rederived them into an enhanced barrier facility to standardize the microbiota.

MyD88 signaling in dendritic cells and the intestinal epithelium controls immunity against intestinal infection with C. rodentium.

MyD88-mediated signaling downstream of Toll-like receptors and the IL-1 receptor family is critically involved in the induction of protective host responses upon infections. Although it is known that MyD88-deficient mice are highly susceptible to a wide range of bacterial infections, the cell type-specific contribution of MyD88 in protecting the host against intestinal bacterial infection is only poorly understood. In order to investigate the importance of MyD88 in specific immune and nonimmune cell types during intestinal infection, we employed a novel murine knock-in model for MyD88 that enables the cell type-specific reactivation of functional MyD88 expression in otherwise MyD88-deficient mice.

Antibiotics and the Intestinal Microbiome : Individual Responses, Resilience of the Ecosystem, and the Susceptibility to Infections.

The intestinal microbiota is a diverse ecosystem containing thousands of microbial species, whose metabolic activity affects many aspects of human physiology. Large-scale surveys have demonstrated that an individual's microbiota composition is shaped by factors such as diet and the use of medications, including antibiotics. Loss of overall diversity and in some cases loss of single groups of bacteria as a consequence of antibiotic treatment in humans has been associated with enhanced susceptibility toward gastrointestinal infections and with enhanced weight gain and obesity in young children.