Abstract

Colorectal cancer, the third most commonly diagnosed cancer, is a lifestyle disease where diet and gut microbiome contribute intricately in its initiation and progression. Prophylactic bio-interventions mainly probiotics offer an alternate approach towards reducing or delaying its progression. Therefore, the present study was designed wherein a robust protocol for the isolation, characterization, and identification of indigenous probiotics having antigenotoxic and anticancerous activity was followed along with their prophylactic potential assessment in early experimental colorectal carcinogenesis. Among forty-six isolated lactic acid bacterial strains, only three were selected on the basis of antigenotoxicity against N,N-Dimethyl dihydrazine dihydrochloride and 4-Nitroquinoline 1-oxide and probiotic attributes. All three selected probiotic strains exhibited anticancerous potential as is evident by the reduced Aberrant Crypt Foci, reduced fecal pH, enhanced fecal lactic acid bacteria and altered fecal enzymes (β-glucuronidase, nitroreductase, β-glucosidase) that modulated gut microbiota and microenvironment resulting into restored histoarchitecture of the colon. The results are a clear indicator of the prophylactic potential of selected indigenous probiotics which may be used as an alternative prophylactic biological therapy against colon carcinogenesis particularly in highly susceptible individuals.

Highlights

  • Cancer, a heterogeneous disease, is characterized by uncontrolled growth and spread of abnormal cells

  • Ample evidence suggests that colonic microflora is greatly involved in the etiology of colorectal cancer (CRC), dietary interventions and natural bioactive supplements such as probiotics have been studied experimentally extensively to reduce the risk of CRC13,17,20

  • We found that prior supplementation of either established probiotics (L. rhamnosus GG, L. acidophilus) alone or in combination with www.nature.com/scientificreports

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Summary

Introduction

A heterogeneous disease, is characterized by uncontrolled growth and spread of abnormal cells. Several in vitro[7,8], animal studies[9,10,11,12] as well as clinical studies[13,14] have indicated that probiotics have anticancerous attributes against CRC15–18. Probiotics exert their anticancer activity mainly by modulation of gut microbiota, www.nature.com/scientificreports/. Intricate interaction exists between probiotics and immune system which is difficult to evaluate but, the current experimental data gives a clear indication of the modulatory effect of LAB on colonic inflammation, mainly by the restoration of epithelial tight junctions and modulation of T-regulatory cells and their dendritic cells[14,18,20,21]. The present study aimed at isolating LAB targeted against experimental CRC having antigenotoxic and anticancerous potential

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