Abstract

Background and Objective: The cellular microenvironment, diet, and lifestyle play a key role in the occurrence of colorectal cancer. Due to its rising trend, attempts are being made to devise novel biointerventions as adjunct to conventional therapies to prevent this deadly disease. “Metabiotics,” the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. Although beneficial attributes of metabiotics have been elucidated in vitro, yet their anticancer mechanism in vivo needs to be explored. Thus, the present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis.Materials and Methods: Sprague–Dawley rats were daily administered with low, medium, and high dose of metabiotic extract orally along with a single dose of weekly intraperitoneal injection of 1,2-dimethylhydrazine up to 6 weeks and monitored for the markers of early colon carcinogenesis.Results: It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, β-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology.Conclusions: It can be suggested that metabiotics modulate experimental colorectal cancer and could be used as a promising alternative of probiotics, particularly in immunocompromised individuals.

Highlights

  • Colorectal cancer (CRC) remains one of the deadliest cancers with different molecular phenotypes, resistance to chemotherapies, recurrence after surgery, and high mortality rate [1, 2]

  • The present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis

  • It was observed that the medium dose of metabiotic extract attenuated early colon carcinogenesis by reducing fecal procarcinogenic enzymes, oxidants, aberrant crypt foci, vis-à-vis downregulating oncogenes [K-ras, β-catenin, Cox-2, nuclear factor kappa B (NF-κB)] and upregulating tumor suppressor p53 gene leading to almost normal colon histology

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Summary

Introduction

Colorectal cancer (CRC) remains one of the deadliest cancers with different molecular phenotypes, resistance to chemotherapies, recurrence after surgery, and high mortality rate [1, 2]. Pathogenesis of colorectal cancer has been extensively investigated, and there is enough evidence to reveal that genetic mutations accompanied with epigenetic alterations and defective immunological signaling pathways are the chief contributors, which are generally triggered by imbalanced intestinal microbiome. Metabiotics refer to “the structural components of probiotic microorganisms and/or their metabolites and/or signaling molecules with a determined chemical structure that can optimize host-specific physiological functions, regulatory, metabolic and/or behavior reactions connected with the activity of host indigenous microbiota” [7]. “Metabiotics,” the beneficial metabolic signatures of probiotics are emerging as potential anticancer agent due to their ability to alter metabolic processes in the gut lumen and reduce the severity of colon carcinogenesis. The present study was performed to envisage anticancer potential of metabiotic extract obtained from indigenous probiotic, Lactobacillus rhamnosus MD 14, in early experimental colon carcinogenesis

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