Traditional Processed Meat Products Re-designed Towards Inulin-rich Functional Foods Reduce Polyps in Two Colorectal Cancer Animal Models

Abstract

Inulin-rich foods exert a prebiotic effect, as this polysaccharide is able to enhance beneficial colon microbiota populations, giving rise to the in situ production of short-chain fatty acids (SCFAs) such as propionic and butyric acids. These SCFAs are potent preventive agents against colorectal cancer due to their histone deacetylases inhibitory properties, which induce apoptosis in tumor colonocytes. As colorectal cancer is the fourth most common neoplasia in Europe with 28.2 new cases per 100,000 inhabitants, a cost-effective preventive strategy has been tested in this work by redesigning common porcine meat products (chorizo sausages and cooked ham) consumed by a substantial proportion of the population towards potential colorectal cancer preventive functional foods. In order to test the preventive effect of these inulin-rich meat products against colorectal cancer, an animal model (Rattus norvegicus F344) was used, involving two doses of azoxymethane (10 mg/kg) and two treatments with dextran sodium sulfate (DSS) during a 20-week assay period. Control feed, control sausages, functional sausages (15.7% inulin), control cooked ham and functional cooked ham (10% inulin) were used to feed the corresponding animal cohorts. Then, the animals were sacrificed and their digestive tract tissues were analyzed. The results showed a statistically significant 49% reduction in the number of colon polyps in the functional meat products cohorts with respect to the control meat products animals, as well as an increase in the cecum weight (an indicator of a diet rich in prebiotic fiber), a 51.8% increase in colon propionate production, a 39.1% increase in colon butyrate concentrations, and a reduction in the number of hyperplastic Peyer’s patches. Metagenomics studies also demonstrated colon microbiota differences, revealing a significant increase in Bacteroidetes populations in the functional meat products (mainly due to an increase in Bacteroidaceae and Prevotellaceae families, which include prominent propionate producers), together with a reduction in Firmicutes (especially due to lower Lachnospiraceae populations). However, functional meat products showed a remarkable increase in the anti-inflammatory and fiber-fermentative Blautia genus, which belongs to this Lachnospiraceae family. The functional meat products cohorts also presented a reduction in important pro-inflammatory bacterial populations, such as those of the genus Desulfovibrio and Bilophila. These results were corroborated in a genetic animal model of CRC (F344/NSlc-Apc1588/kyo) that produced similar results. Therefore, processed meat products can be redesigned towards functional prebiotic foods of interest as a cost-effective dietary strategy for preventing colorectal cancer in human populations.

Emerging Evidence on the Effects of Dietary Factors on the Gut Microbiome in Colorectal Cancer

“…This change in taxonomical traits were associated with reduced expression of pro-oncogenic miR17-92, protective against CRC [41]. Functional foods such as processed meat fortified with polysaccharide inulin increases the abundance of anti-inflammatory and fiber fermentative Blautia genus which increase SCFAs like propionate and butyrate [42]. This has shown to reduce colonic polyps in experimental rats possibly due to the anti-inflammatory effects.…”

Preventing Colorectal Cancer through Prebiotics

“…Similarly, this prebiotic, along with the commercial probiotic VSL#3 ® (Sigma-Tau Pharmaceuticals, Gaithersburg, MD, USA) showed extra benefits in C57BL6/J mice, in comparison with the use of VSL#3 ® alone, culminating in a significant reduction in precursor lesions of CRC [ 26 ]. In other new researches on rats developing CRC, either genetically or by induction carcinogens such as AOM/DSS, various prebiotics such as galacto-oligosaccharides derived from lactulose [ 27 ], inulin [ 28 ], phenolic compounds such as anthocyanins and ellagic acid from Myrciaria jaboticaba ((Vell.) O.Berg) seeds [ 29 ], and Djulis ( Chenopodium formosanum ), a native cereal crop [ 30 ], had preventive effects against CRC progression ( Table 2 ).…”

“…These nutrients drive the decline or growth of certain bacterial groups depending on the type of prebiotic [ 40 ]. Studies indicated that inulin-rich foods can enhance prominent propionate producers in Bacteroidetes populations, mainly due to a significant increase in the Bacteroidaceae , Porphyromonadaceae , and especially Prevotellacea families [ 28 ]. Inulin also helps to reduce the phylum Firmicutes , primarily due to lower Lachnospiraceae populations.…”

“…Therefore, the lower ratio demonstrated in this study indicated a protective effect of inulin. In addition, consumption of inulin led to a substantial reduction in pro-inflammatory bacterial populations, such as those related to the genus Desulfovibrio and Bilophila [ 28 ]. Furthermore, in a recent research on rats with induced CRC, prebiotic phenolic compounds such as anthocyanins, ellagic acid, and ellagitannins were able to restore the biodiversity of bacteria in all groups by changing the abundance of Firmicutes , Bacteroidetes , and Proteobacteria phyla [ 29 ].…”

“…For example, Yacón flour as a source of fructooligosaccharides in animals with induced colorectal carcinogenesis induces greater production of acetic, propionic, and butyric acids, and total SCFAs [ 25 ]. In addition, inulin-rich foods give rise to the in situ production of SCFAs such as propionic and butyric acids [ 28 ] or lactulose, thus causing a significant increase in the production of propionate [ 27 ]. Furthermore, there is compelling evidence for the release of butyrate from acacia gum consumption [ 22 ], and a higher production of acetate along with butyrate by using NVPS [ 21 ] and chitin-glucan [ 24 ].…”