title: Persistent hyperglycemia modulates gut immune function and microbiota in rats.
abstract: BACKGROUND
  Since hyperglycemia-induced cellular dysfunction could be associated with alterations of the immune system, we tested the hypothesis that hyperglycemia augments the aberrant immune responses such as inflammation and differentiation of CD4(+) T lymphocytes in the mesenteric lymph nodes (MLNs), and induces alterations of microbiota both under physiological and pathological conditions.
  
  
  METHODS
  Male Wistar rats were randomly allocated into 4 groups: Control and Endotoxemia (lipopolysaccharide, LPS 1 mg/kg) with or without hyperglycemia. The hyperglycemia groups were administered glucose solution (10-40 %), while the normoglycemia groups were administered saline. Alterations of the mRNA expressions of inflammatory cytokines and CD4(+) T lymphocyte transcriptional factor expressions in the MLNs, and those of the intestinal microbiota were analyzed at 24 hr.
  
  
  RESULTS
  Hyperglycemia was kept approximately 250-350 mg/dL during the 24 hr study period. At the end of 24 hr, hyperglycemia augmented the mRNA expressions of interleukin (IL)-1β and IL-6 in the MLNs, while both the helper T (Th) 2 and regulatory-T (Treg) transcriptional factors were simultaneously up-regulated under non-endotoxemic condition. LPS injection significantly modulated the obligate anaerobe bacterial populations of the Bacteroidetes class, and altered the population sizes of the Clostridium perfringens and the Bacteroides fragilis subgroup. Hyperglycemia did not enhance these alterations of the microbiota evoked by LPS, although it did modify the bacterial populations of the L. reuteri subgroup and staphylococci in healthy condition without endotoxemia.
  
  
  CONCLUSIONS
  The present study indicates that both gut immune function and microbiota are significantly modulated by persistent hyperglycemia.
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Katsuya
authors.initials: K
authors.lastname: Mori
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Toru
authors.initials: T
authors.lastname: Igarashi
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Inoue
authors.affiliation: Yakult Central Institute for Microbiological Research, 5-11 Izumi, Kunitachi-shi, Tokyo 186-0012 Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Asahara
authors.affiliation: Yakult Central Institute for Microbiological Research, 5-11 Izumi, Kunitachi-shi, Tokyo 186-0012 Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Nomoto
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Seki
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Takashige
authors.initials: T
authors.lastname: Yamada
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Shizuka
authors.initials: S
authors.lastname: Minamishima
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Shizuko
authors.initials: S
authors.lastname: Kosugi
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Katori
authors.affiliation: Department of Anesthesiology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160-8582 Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Morisaki
keywords: CD4+ T lymphocyte subsets; Gut barrier function; Mesenteric lymph nodes; Pro-inflammatory cytokine