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Chemopreventive Effects of Cranberry in Association with the Alteration of Gut Microbiota

Abstract
Accumulating evidence showed that microbiota play important roles in colonic inflammation and inflammation-associated colon carcinogenesis. Fruits and vegetable are known to have protective effects against colon carcinogenesis. Cranberry fruit contains large amount of flavonoids, phenolic acids and dietary fiber, which has been studied for their potential chemopreventive effect from in vitro model. To better understand the effect, we studied the protective effects of whole cranberry powder against colitis in mice treated with dextran sulfate sodium (DSS) and inflammation-associated colon carcinogenesis in mic treated with azoxymethane (AOM) and DSS, and its impact on gut microbiota. In DSS-induced colitis mice model, 1.5% (w/w) whole cranberry powder mixed with regular diet was provided to mice for 32 days. The oral administration of cranberry powder significantly reduced the DAI score and inhibited the inflammation in the colon compared to the control group. Moreover, cranberry diet increase the richness and evenness of gut microbiota in mice, which played an important role on inflammation prevention. Oral intake of cranberry can significantly inhibited the growth of Akkermansia and Sutterella while protect the growth of Bifidobacterium and Lactobacillus. In AOM-induced colonic cancer mice model, whole cranberry powder was administered to mice through diet at 1.5% w/w for 20 weeks. Our results demonstrated that treatment with cranberry powder significantly reduced the incidence and multiplicity of colon tumors. These protective effects were associated with decreased inflammation and increased apoptosis in the colonic tumors. Using 16s rRNA amplicon sequencing, we analyzed the structure and predicted the function of fecal microbiota of the mice. Compared to that of the negative control group, fecal microbiota of AOM/DSS-treated mice showed relative abundance shifts, a decrease of the abundance of Akkmansia. Dietary treatment with whole cranberry powder reversed aforementioned alterations in the fecal microbiota of AOM/DSS-treated mice. Moreover, whole cranberry powder also increased the number of Bifidobacterium and Lactobacillus in the fecal microbiota. These composition alterations induced by whole cranberry powder were associated with suppressed colonic inflammation and carcinogenesis. In conclusion, our results demonstrated that whole cranberry powder modulated the composition of gut microbiota in both DSS-treated and AOM/DSS-treated mice, which may contribute to its anti-inflammatory and anti-carcinogenic effects in the colon.
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dissertation
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