Treatment with Subcritical Water-Hydrolyzed Citrus Pectin Ameliorated Cyclophosphamide-Induced Immunosuppression and Modulated Gut Microbiota Composition in ICR Mice

Molecules. 2020 Mar 12;25(6):1302. doi: 10.3390/molecules25061302.

Abstract

Subcritical water can effectively hydrolyze pectin into smaller molecules while still maintaining its functional regions. Pectic heteropolysaccharide can mediate immune regulation; however, the possible effects of subcritical water-hydrolyzed citrus pectin (SCP) on the immune response remain unclear. Therefore, the effects of SCP on immunomodulatory functions and intestinal microbial dysbiosis were investigated using a cyclophosphamide-induced immunosuppressed mouse model. In this research, immunosuppressed ICR mice were administrated with SCP at dosages of 300/600/1200 mg/kg.bw by oral gavage, and body weight, immune organ indexes, cytokines, and gut microbiota were determined. The results showed that subcritical water treatment decreased the molecular mass and increased the content of galacturonic acid in citrus pectin hydrolysates. Meanwhile, the treatment with SCP improved immunoregulatory functional properties and bioactivities over the original citrus pectin. For example, SCP protected immune organs (accelerated recovery of immune organ indexes) and significantly enhanced the expression of immune-related cytokines (IL-2, IL-6, IFN-γ, and TNF-α). The results of the 16S rDNA sequencing analysis on an IlluminaMiSeq platform showed that SCP normalized Cy-induced gut dysbiosis. SCP ameliorated Cy-dependent changes in the relative abundance of several taxa, shifting the balance back to normal status (e.g., SCP increased beneficial Muribaculaceae, Ruminococcaceae, Bacteroidaceae, and Prevotellaceae while decreasing pathogenic Brevundimonas and Streptococcus). The results of this study suggest an innovative application of citrus pectin as an immunomodulator.

Keywords: Citrus pectin; Cyclophosphamide; Gut microbiota; Immunosuppression; Subcritical-water.

MeSH terms

  • Animals
  • Citrus / chemistry*
  • Cyclophosphamide / immunology
  • Cyclophosphamide / toxicity
  • Gastrointestinal Microbiome / drug effects*
  • Gastrointestinal Microbiome / immunology
  • Humans
  • Immunosuppression Therapy*
  • Mice
  • Mice, Inbred ICR
  • Pectins / chemistry
  • Pectins / pharmacology*
  • Water / chemistry

Substances

  • Water
  • Pectins
  • Cyclophosphamide