Persistent hyperglycemia modulates gut immune function and microbiota in rats

Katsuya Mori, Takeshi Suzuki, Toru Igarashi, Kei Inoue, Takashi Asahara, Koji Nomoto, Hiroyuki Seki, Takashige Yamada, Shizuka Minamishima, Shizuko Kosugi, Nobuyuki Katori, Hiroshi Morisaki

Research output: Contribution to journalArticle

1 Citation (Scopus)

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.

Original languageEnglish
Article number34
JournalJournal of Intensive Care
Volume3
Issue number1
DOIs
Publication statusPublished - 2015 Jul 23

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Microbiota
Hyperglycemia
Endotoxemia
Lymph Nodes
Bacteroidetes
T-Lymphocytes
Bacteroides fragilis
Messenger RNA
Clostridium perfringens
Population Density
Interleukin-1
Staphylococcus
Population
Lipopolysaccharides
Wistar Rats
Immune System
Interleukin-6
Cytokines
Inflammation
Glucose

Keywords

  • CD4 T lymphocyte subsets
  • Gut barrier function
  • Mesenteric lymph nodes
  • Pro-inflammatory cytokine

ASJC Scopus subject areas

  • Critical Care and Intensive Care Medicine

Cite this

Persistent hyperglycemia modulates gut immune function and microbiota in rats. / Mori, Katsuya; Suzuki, Takeshi; Igarashi, Toru; Inoue, Kei; Asahara, Takashi; Nomoto, Koji; Seki, Hiroyuki; Yamada, Takashige; Minamishima, Shizuka; Kosugi, Shizuko; Katori, Nobuyuki; Morisaki, Hiroshi.

In: Journal of Intensive Care, Vol. 3, No. 1, 34, 23.07.2015.

Research output: Contribution to journalArticle

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AU - Mori, Katsuya

AU - Suzuki, Takeshi

AU - Igarashi, Toru

AU - Inoue, Kei

AU - Asahara, Takashi

AU - Nomoto, Koji

AU - Seki, Hiroyuki

AU - Yamada, Takashige

AU - Minamishima, Shizuka

AU - Kosugi, Shizuko

AU - Katori, Nobuyuki

AU - Morisaki, Hiroshi

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KW - Pro-inflammatory cytokine

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