title: Correlation between protection against sepsis by probiotic therapy and stimulation of a novel bacterial phylotype.
abstract: Prophylactic probiotic therapy has shown beneficial effects in an experimental rat model for acute pancreatitis on the health status of the animals. Mechanisms by which probiotic therapy interferes with severity of acute pancreatitis and associated sepsis, however, are poorly understood. The aims of this study were to identify the probiotic-induced changes in the gut microbiota and to correlate these changes to disease outcome. Duodenum and ileum samples were obtained from healthy and diseased rats subjected to pancreatitis for 7 days and prophylactically treated with either a multispecies probiotic mixture or a placebo. Intestinal microbiota was characterized by terminal-restriction fragment length polymorphism (T-RFLP) analyses of PCR-amplified 16S rRNA gene fragments. These analyses showed that during acute pancreatitis the host-specific ileal microbiota was replaced by an "acute pancreatitis-associated microbiota." This replacement was not reversed by administration of the probiotic mixture. An increase, however, was observed in the relative abundance of a novel bacterial phylotype most closely related to Clostridium lituseburense and referred to as commensal rat ileum bacterium (CRIB). Specific primers targeting the CRIB 16S rRNA gene sequence were developed to detect this phylotype by quantitative PCR. An ileal abundance of CRIB 16S rRNA genes of more than 7.5% of the total bacterial 16S rRNA gene pool was correlated with reduced duodenal bacterial overgrowth, reduced bacterial translocation to remote organs, improved pancreas pathology, and reduced proinflammatory cytokine levels in plasma. Our current findings and future studies involving this uncharacterized bacterial phylotype will contribute to unraveling one of the potential mechanisms of probiotic therapy.
authors.affiliation: Laboratory of Microbiology, Wageningen University, Dreijenplein 10, 6703 HB Wageningen, The Netherlands. jacoline.gerritsen@wur.nl
authors.forename: Jacoline
authors.initials: J
authors.lastname: Gerritsen
authors.forename: Harro M
authors.initials: HM
authors.lastname: Timmerman
authors.forename: Susana
authors.initials: S
authors.lastname: Fuentes
authors.forename: L Paul
authors.initials: LP
authors.lastname: van Minnen
authors.forename: Henk
authors.initials: H
authors.lastname: Panneman
authors.forename: Sergey R
authors.initials: SR
authors.lastname: Konstantinov
authors.forename: Frans M
authors.initials: FM
authors.lastname: Rombouts
authors.forename: Hein G
authors.initials: HG
authors.lastname: Gooszen
authors.forename: Louis M A
authors.initials: LM
authors.lastname: Akkermans
authors.forename: Hauke
authors.initials: H
authors.lastname: Smidt
authors.forename: Ger T
authors.initials: GT
authors.lastname: Rijkers
mesh_terms: D000818:Animals; D044822:Biodiversity; D001691:Biological Therapy / Q000379:methods*; D003013:Clostridium / Q000145:classification* / Q000235:genetics / Q000302:isolation & purification; D016000:Cluster Analysis; D004269:DNA, Bacterial / Q000737:chemistry / Q000235:genetics; D004275:DNA, Ribosomal / Q000737:chemistry / Q000235:genetics; D004386:Duodenum / Q000382:microbiology; D041981:Gastrointestinal Tract / Q000382:microbiology*; D007082:Ileum / Q000382:microbiology; D008969:Molecular Sequence Data; D019283:Pancreatitis, Acute Necrotizing / Q000150:complications*; D010802:Phylogeny; D012150:Polymorphism, Restriction Fragment Length; D019936:Probiotics / Q000008:administration & dosage*; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D018805:Sepsis / Q000517:prevention & control*; D017422:Sequence Analysis, DNA
chemical_list: D004269:DNA, Bacterial; D004275:DNA, Ribosomal; D012336:RNA, Ribosomal, 16S