Host Genetics and Environmental Factors Regulate Ecological Succession of the Mouse Colon Tissue-Associated Microbiota

Background: The integration of host genetics, environmental triggers and the microbiota is a recognised factor in the pathogenesis of barrier function diseases such as IBD. In order to determine how these factors interact to regulate the host immune response and ecological succession of the colon tissue-associated microbiota, we investigated the temporal interaction between the microbiota and the host following disruption of the colonic epithelial barrier. Methodology/Principal Findings: Oral administration of DSS was applied as a mechanistic model of environmental damage of the colon and the resulting inflammation characterized for various parameters over time in WT and Nod2 KO mice. Results: In WT mice, DSS damage exposed the host to the commensal flora and led to a migration of the tissue-associated bacteria from the epithelium to mucosal and submucosal layers correlating with changes in proinflammatory cytokine profiles and a progressive transition from acute to chronic inflammation of the colon. Tissue-associated bacteria levels peaked at day 21 post-DSS and declined thereafter, correlating with recruitment of innate immune cells and development of the adaptive immune response. Histological parameters, immune cell infiltration and cytokine biomarkers of inflammation were indistinguishable between Nod2 and WT littermates following DSS, however, Nod2 KO mice demonstrated significantly higher tissue-associated bacterial levels in the colon. DSS damage and Nod2 genotype independently regulated the community structure of the colon microbiota

Bi-galileon theory II: phenomenology

We continue to introduce bi-galileon theory, the generalisation of the single galileon model introduced by Nicolis et al. The theory contains two coupled scalar fields and is described by a Lagrangian that is invariant under Galilean shifts in those fields. This paper is the second of two, and focuses on the phenomenology of the theory. We are particularly interesting in models that admit solutions that are asymptotically self accelerating or asymptotically self tuning. In contrast to the single galileon theories, we find examples of self accelerating models that are simultaneously free from ghosts, tachyons and tadpoles, able to pass solar system constraints through Vainshtein screening, and do not suffer from problems with superluminality, Cerenkov emission or strong coupling. We also find self tuning models and discuss how Weinberg's no go theorem is evaded by breaking Poincar\'e invariance in the scalar sector. Whereas the galileon description is valid all the way down to solar system scales for the self-accelerating models, unfortunately the same cannot be said for self tuning models owing to the scalars backreacting strongly on to the geometry