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Clostridium butyricum CGMCC0313.1 Protects against Autoimmune Diabetes by Modulating Intestinal Immune Homeostasis and Inducing Pancreatic Regulatory T Cells

  • 2017-10-19
  • Frontiers in Immunology 8
    • Lingling Jia
    • Kai Shan
    • Li-Long Pan
    • Ninghan Feng
    • Zhuwu Lv
    • Yajun Sun
    • Jiahong Li
    • Chengfei Wu
    • Hao Zhang
    • Wei Chen
    • J. Diana
    • Jia Sun
    • Yong Q. Chen

Abstract

Recent evidence indicates that indigenous Clostridium species induce colonic regulatory T cells (Tregs), and gut lymphocytes are able to migrate to pancreatic islets in an inflammatory environment. Thus, we speculate that supplementation with the well-characterized probiotics Clostridium butyricum CGMCC0313.1 (CB0313.1) may induce pancreatic Tregs and consequently inhibit the diabetes incidence in non-obese diabetic (NOD) mice. CB0313.1 was administered daily to female NOD mice from 3 to 45 weeks of age. The control group received an equal volume of sterile water. Fasting glucose was measured twice a week. Pyrosequencing of the gut microbiota and flow cytometry of mesenteric lymph node (MLN), pancreatic lymph node (PLN), pancreatic and splenic immune cells were performed to investigate the effect of CB0313.1 treatment. Early oral administration of CB0313.1 mitigated insulitis, delayed the onset of diabetes, and improved energy metabolic dysfunction. Protection may involve increased Tregs, rebalanced Th1/Th2/Th17 cells and changes to a less proinflammatory immunological milieu in the gut, PLN, and pancreas. An increase of α4β7+ (the gut homing receptor) Tregs in the PLN suggests that the mechanism may involve increased migration of gut-primed Tregs to the pancreas. Furthermore, 16S rRNA gene sequencing revealed that CB0313.1 enhanced the Firmicutes/Bacteroidetes ratio, enriched Clostridium-subgroups and butyrate-producing bacteria subgroups. Our results provide the basis for future clinical investigations in preventing type 1 diabetes by oral CB0313.1 administration.

Keywords: butyrate-producing bacteria; gut microbiota; regulatory T cells; regulatory T cells migration; type 1 diabetes.

Research Insights

SupplementHealth OutcomeEffect TypeEffect Size
Clostridium butyricumDelayed Onset of Type 1 DiabetesBeneficial
Large
Clostridium butyricumImproved Energy MetabolismBeneficial
Moderate
Clostridium butyricumImproved Gut Microbiome CompositionBeneficial
Large
Clostridium butyricumIncreased Regulatory T Cell CountBeneficial
Moderate
Clostridium butyricumRebalanced Th1/Th2/Th17 Cell RatiosBeneficial
Moderate
Clostridium butyricumReduced InflammationBeneficial
Moderate

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