Pretreatment with the probiotic VSL#3 delays transition from inflammation to dysplasia in a rat model of colitis-associated cancer

Abstract

Evidence supports involvement of microflora in the transition of chronic inflammation to neoplasia. We investigated the protective efficacy of the probiotic VSL#3 in a model of colitis-associated colorectal cancer. Chronic colitis was induced in Sprague-Dawley rats by administration of trinitrobenzene sulfonic acid (TNBS), followed 6 wk later by systemic reactivation. To induce colitis-associated dysplasia and cancer, the animals received TNBS (intravenously) twice a week for 10 wk. One group received VSL#3 in drinking water from 1 wk before colitis induction until death. The colons were examined for damage and presence of dysplasia or cancer. Samples were analyzed for cell proliferation and apoptosis, vitamin D receptor (VDR) expression, angiogenic factors, and presence of alkaline sphingomyelinase or phosphatase. Microbial community composition was evaluated by terminal restriction fragment-length polymorphism analysis of the bacterial 16S rRNA gene. None of the probiotic-treated animals developed carcinoma, and no high-grade dysplasia was found in either the proximal or mid colon. In contrast, 29% of the animals in the control group developed carcinoma in one or more regions of the colon. VSL#3-treated animals had significantly less damage than the vehicle treated-controls in all areas of the colon, and this correlated with decreased richness and diversity of the mucosally adherent microbiota. Treatment with the probiotic increased the antiangiogenic factor angiostatin, VDR expression, and alkaline sphingomyelinase. We concluded that pretreatment with the probiotic VSL#3 can attenuate various inflammatory-associated parameters, delaying transition to dysplasia and cancer, thus offering its potential therapeutic use in patients with long-standing colitis.

Probiotics modify human intestinal mucosa-associated microbiota in patients with colorectal cancer

“…A lower diversity was present in the gut microflora in patients with CRC, which was associated with the increased abundance of certain pathogens. The results were consistent with those of previous studies (38). Probiotic treatment of patients with CRC can improve the abundance of gut microflora by enhancing the diversity of the microbiota to approach a normal level (43).…”

“…Numerous studies have demonstrated that consumption of certain probiotics or prebiotics, which have been applied to various medical conditions, is able to favorably alter the pre-disposing factors of CRC, and is a promising approach for prevention of CRC (38). In vitro studies have demonstrated that lactic acid bacteria significantly reduce the growth and viability of the human colon cancer cell line HT-29 (39).…”

Significant differences in fecal microbiota are associated with various stages of glucose tolerance in African American male veterans

“…2,43 Our research is an extension of the basic hypothesis that vitamin D deficiency is a significant contributor to risk of T2DM. 20,22 In particular, based on preclinical studies, 44-46 we hypothesized that vitamin D deficiency would further lead to an alteration in gut microbial community structure, and this would be observable in analyses of fecal samples.…”

Immunotoxic and Genotoxic Effects of Arsenic and Ameliorative Potential of Quercetin and Probiotics in Wistar Rat

“…The rats were given fresh water through glass bottles with a capillary dropper fixed to the wall of the cage. Animals were divided into six groups (n=15) and were orally treated by gastric tube for 4 weeks as follows: Group I control animals were given a 2 mL daily dose of distilled water; Group II animals received NaAsO 2 daily at a dose of 5 mg kg -1 dissolved in water as the minimum dose that induces toxicity in the rats [17]; Group III animals received quercetin at a dose of 50 mg kg -1 dissolved in water [18]; Group IV animals were administered probiotic at dose of 2 mL containing 2 × 10 9 colony forming units (cfu) dissolved in water [19]; Group V and Group VI animals received NaAsO 2 (5 mg kg -1 ) and were treated orally with quercetin (50 mg kg -1 ) and probiotic (2 × 10 9 cfu), respectively.…”