title: The long and winding road to gut homeostasis.
abstract: OBJECTIVE
  The open ecosystem of the alimentary tract, harboring approximately 1 kg of bacteria, exhibits a rapid, but tightly controlled turnover. Impaired nuclear receptor function can give rise to perturbation in the gut, leading to inflammation and possibly neoplasia. Intriguingly, bacteria-dependent signaling pathways can modulate, and in turn be modulated by, a subset of nuclear receptors. This review attempts to highlight how microbes and nuclear receptors could jointly regulate gut homeostasis.
  
  
  RESULTS
  Commensal bacteria can utilize peroxisome proliferator activated receptor-gamma-dependent nuclear export of RelA as a novel mechanism to attenuate inflammatory signals triggered by a pathogen. Other nuclear receptors, such as liver X receptor, vitamin D receptor and farnesoid X receptor were also recently shown to interact with bacteria-induced mammalian inflammatory pathways. Although details of this interplay are still being unraveled, a role for these and other nuclear receptors in gastrointestinal inflammation and possibly neoplasia is beyond dispute.
  
  
  CONCLUSIONS
  The commensal microflora is being accorded due importance in regulating homeostasis of the gastrointestinal tract. Recent data suggest that the molecular messengers used by these bacteria include nuclear receptors. Exploiting mechanisms of nuclear receptor activity as drug targets, together with a detailed knowledge of the microbiota, could improve our understanding of gut-related ailments, and aid in mitigating their symptoms.
authors.affiliation: Microbiology Tumorbiology Center, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Velmurugesan
authors.initials: V
authors.lastname: Arulampalam
authors.forename: Gediminas
authors.initials: G
authors.lastname: Greicius
authors.forename: Sven
authors.initials: S
authors.lastname: Pettersson
mesh_terms: D000818:Animals; D001419:Bacteria / Q000254:growth & development / Q000378:metabolism; D018450:Disease Progression; D041981:Gastrointestinal Tract / Q000378:metabolism* / Q000382:microbiology; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D015212:Inflammatory Bowel Diseases / Q000378:metabolism* / Q000382:microbiology; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism
chemical_list: D018160:Receptors, Cytoplasmic and Nuclear