title: Helicobacter hepaticus increases intestinal injury in a rat model of necrotizing enterocolitis.
abstract: Enterohepatic helicobacter species (EHS) infect the intestinal tract and biliary tree, triggering intestinal and hepatic disorders. Helicobacter hepaticus, the prototypic murine EHS, is also associated with inflammation. Necrotizing enterocolitis (NEC) is a devastating disease of premature infants. The cause of NEC is not fully understood, but anomalies of bacterial colonization (dysbiosis) are thought to play an important role in disease onset. To evaluate the effect of H. hepaticus infection on the development of NEC, premature formula-fed rats were kept either in H. hepaticus-free conditions or colonized with H. hepaticus; both groups were exposed to asphyxia and cold stress. The incidence of NEC, expression of Toll-like receptors (TLRs), production of cytokines and mucins, and presence of autophagy regulators were evaluated at the site of injury. H. hepaticus infection increased the incidence of NEC from 39 to 71% and significantly increased levels of TLR4 receptor, expression of proinflammatory cytokines CXCL1, IL-1β, IL-12, and IL-23, and altered activation of autophagy. H. hepaticus induces inflammation and increases the incidence and severity of experimental NEC; this is consistent with observations in neonates of blooms of proinflammatory microbes just before the onset of NEC. Future studies using rodent NEC models should include testing for H. hepaticus infection. Further studies in neonates of early identification and/or diminution of proinflammatory microbes may be beneficial in decreasing the incidence of NEC.
authors.affiliation: Dept. of Pediatrics, NorthShore Univ. HealthSystem, 2650 Ridge Ave., Evanston, IL 60201. bdvorak@northshore.org.
authors.forename: Katerina
authors.initials: K
authors.lastname: Dvorak
authors.forename: Christine F
authors.initials: CF
authors.lastname: Coursodon-Boyiddle
authors.forename: Chelsea L
authors.initials: CL
authors.lastname: Snarrenberg
authors.forename: Anchasa
authors.initials: A
authors.lastname: Kananurak
authors.forename: Mark A
authors.initials: MA
authors.lastname: Underwood
authors.forename: Bohuslav
authors.initials: B
authors.lastname: Dvorak
mesh_terms: D000818:Animals; D001343:Autophagy; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020345:Enterocolitis, Necrotizing / Q000382:microbiology* / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D016481:Helicobacter Infections / Q000382:microbiology* / Q000473:pathology; D044923:Helicobacter hepaticus / Q000502:physiology*; D007082:Ileum / Q000378:metabolism / Q000382:microbiology / Q000473:pathology; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D012329:RNA, Bacterial / Q000302:isolation & purification; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D016207:Cytokines; D012329:RNA, Bacterial
keywords: autophagy; cytokines; enteral bacteria; mucosal inflammation