Behaviour of citrus pectin and modified citrus pectin in an azoxymethane/dextran sodium sulfate (AOM/DSS)-induced rat colorectal carcinogenesis model

Int J Biol Macromol. 2021 Jan 15:167:1349-1360. doi: 10.1016/j.ijbiomac.2020.11.089. Epub 2020 Nov 14.

Abstract

Large intestine cancer is one of the most relevant chronic diseases taking place at present. Despite therapies have evolved very positively, this pathology is still under deep investigation. One of the recent approaches is the prevention by natural compounds such as pectin. In this paper, we have assessed the impact of citrus pectin and modified citrus pectin on colorectal cancer in rats (Rattus norvegicus F344) to which azoxymethane and DSS were supplied. The lowest intake of food and body weight were detected in animals fed with citrus pectin, together with an increase in the caecum weight, probably due to the viscosity, water retention capacity and bulking properties of pectin. The most striking feature was that, neither citrus pectin nor modified citrus pectin gave rise to a tumorigenesis prevention. Moreover, in both, more than 50% of rats with cancer died, probably ascribed to a severe dysbiosis state in the gut, as shown by the metabolism and metagenomics studies carried out. This was related to a decrease of pH in caecum lumen and increase in acetate and lactic acid levels together with the absence of propionic and butyric acids. A relevant increase in Proteobacteria (Enterobacteriaceae) were thought to be one of the reasons for enteric infection that could have provoked the death of rats and the lack of cancer prevention. However, a reduction of blood glucose and triacylglycerides level and an increase of Bifidobacterium and Lactobacillaceae were found in animals that intake pectin, as compared to universal and modified citrus pectin feeding.

Keywords: Acetic acid; Cancer; Dysbiosis; Gut; Intestinal microbiota; Lactic acid; pH decrease.

MeSH terms

  • Acetates / metabolism
  • Animals
  • Azoxymethane / pharmacology
  • Azoxymethane / toxicity*
  • Bifidobacterium / isolation & purification
  • Blood Glucose / drug effects
  • Body Weight / drug effects
  • Butyrates / metabolism
  • Carcinogenesis / drug effects*
  • Carcinogenesis / metabolism
  • Carcinogenesis / pathology
  • Chromatography, High Pressure Liquid
  • Citrus / chemistry
  • Colorectal Neoplasms / chemically induced
  • Colorectal Neoplasms / diet therapy*
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / mortality
  • Dextran Sulfate / pharmacology
  • Disease Models, Animal
  • Gastrointestinal Microbiome / drug effects*
  • Hydrogen-Ion Concentration
  • Lactic Acid / metabolism
  • Lactobacillaceae / isolation & purification
  • Male
  • Metagenomics
  • Pectins / analysis
  • Pectins / therapeutic use*
  • Phylogeny
  • Propionates / metabolism
  • Proteobacteria / isolation & purification
  • Rats
  • Rats, Inbred F344
  • Triglycerides / blood

Substances

  • Acetates
  • Blood Glucose
  • Butyrates
  • Propionates
  • Triglycerides
  • Lactic Acid
  • citrus pectin
  • Pectins
  • Dextran Sulfate
  • propionic acid
  • Azoxymethane