Oligofructans from Bacillus subtilis TISTR 001-fermented sugar: Anticarcinogenic effect and gut microbiota modulation in a rat model of 1,2-dimethylhydrazine-induced colon carcinogenesis

Prebiotics are non-digestible food components that have been extensively researched for their role in preventing and managing colon cancer. Our previous study produced oligofructans by fermenting sugar with Bacillus subtilis TISTR 001, which possesses prebiotic properties. To date, no studies have reported its chemopreventive effects on colon cancer in animal models. Therefore, this study aimed to evaluate the anticarcinogenic effects of oligofructans against 1,2-dimethylhydrazine (DMH)-induced rat colon carcinogenesis and to explore possible mechanisms. DMH (40 mg/kg) was subcutaneously injected twice to induce colorectal cancer in rats. Rats were orally administered oligofructans at doses of 100 and 500 mg/kg for 15 weeks to investigate carcinogenic and anticarcinogenic properties. Treatment with oligofructans at both 100 and 500 mg/kg did not induce the formation of colonic aberrant crypt foci (ACF), demonstrating no carcinogenic activity. Interestingly, it significantly reduced the number of ACF in rats initiated with DMH. Mechanistic studies indicated that a low dose of oligofructans significantly down-regulated the expression of genes related to inflammation ( NF-κB, COX-2, and iNOS ) and cell proliferation ( cyclin D1 and cyclin E ). Similar results were observed with a high dose of oligofructans, which significantly down-regulated the expression of APC and β-catenin genes, as well as genes related to apoptosis ( p53 and Bax ). Treatment with oligofructans did not influence the dominant gut microbiota but significantly affected low-abundance phyla, such as Candidatus Absconditabacteria , and specific bacterial taxa, including Ligilactobacillus salivarius . These findings highlight the selective modulatory effect of oligofructans on the gut microbiome, supporting their potential as a functional food component for preventing colon carcinogenesis. • Oligofructans significantly suppress DMH-induced rat colon carcinogenesis. • Oligofructans exert anti-inflammatory, antiproliferative, and pro-apoptotic effects. • Oligofructans specifically modulate the composition of low-abundance gut microbiota.