Dietary Aloe Vera Gel Powder and Extract Inhibit Azoxymethane-induced Colorectal Aberrant Crypt Foci in Mice Fed a High-fat Diet

High-fat diet (HFD)-induced alteration in the gut microbial composition, known as dysbiosis, is increasingly recognized as a major risk factor for various diseases, including colon cancer. This report describes a comprehensive investigation of the effect of agaro-oligosaccharides (AGO) on HFD-induced gut dysbiosis, including alterations in short-chain fatty acid contents and bile acid metabolism in mice. C57BL/6N mice were fed a control diet or HFD, with or without AGO. Terminal restriction fragment-length polymorphism (T-RFLP) analysis produced their fecal microbiota profiles. Profiles of cecal organic acids and serum bile acids were determined, respectively, using HPLC and liquid chromatography-tandem mass spectrometry systems. T-RFLP analyses showed that an HFD changed the gut microbiota significantly. Changes in the microbiota composition induced by an HFD were characterized by a decrease in the order Lactobacillales and by an increase in the Clostridium subcluster XIVa. These changes of the microbiota community generated by HFD treatment were suppressed by AGO supplementation. As supported by the data of the proportion of Lactobacillales order, the concentration of lactic acid increased in the HFD + AGO group. Data from the serum bile acid profile showed that the level of deoxycholic acid, a carcinogenic secondary bile acid produced by gut bacteria, was increased in HFD-receiving mice. The upregulation tended to be suppressed by AGO supplementation. Finally, results show that AGO supplementation suppressed the azoxymethane-induced generation of aberrant crypt foci in the colon derived from HFD-treated mice. Our results suggest that oral intake of AGO prevents HFD-induced gut dysbiosis, thereby inhibiting colon carcinogenesis.

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Azoxymethane Alters the Plasma Metabolome to a Greater Extent in Mice Fed a High Fat Diet Compared to AIN-93 Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzab036_031 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 289-289

Author(s):

Huawei Zeng ◽

Shahid Umar ◽

Zhenhua Liu ◽

Michael Bukowski

Keyword(s):

Colon Cancer ◽

High Fat Diet ◽

Agricultural Research ◽

Tca Cycle ◽

Aberrant Crypt Foci ◽

Alpha Tocopherol ◽

Service Research ◽

Cancer Model ◽

High Fat ◽

Plasma Metabolome

Abstract Objectives Consumption of a high fat diet (HFD) links obesity to colon cancer in humans. Consistent with this observation, our data show that a HFD (45% energy fat versus 16% energy fat in AIN-93 diet, AIN) promotes azoxymethane (AOM) induced colonic aberrant crypt foci (ACF) formation in a mouse cancer model. However, the underlying metabolic basis remains to be determined. We hypothesize that AOM treatment results in different plasma metabolomic responses in AOM mouse colon cancer model fed with a HFD compared to the AIN. Methods Four-week-old male C57BL/6 mice were fed the AIN or HFD in the context of with or without AOM treatment for 16 weeks. At the end of this study, plasma samples were extracted and derivatized by silylation and methyloximation then analyzed by time-of-flight mass spectrometry using an untargeted metabolomic technique. Results Untargeted metabolomic profiling showed that 53 of 144 identified metabolites were different between the 4 groups of mice (AIN only, AIN + AOM; HFD only, HFD + AOM). Sparse partial least squares discriminant analysis (two-dimensional plots) showed a separation between the HFD and HFD + AOM groups but not AIN and AIN + AOM groups. Major metabolites responsible for this separation were beta-sitosterol, dihydrocholesterol, alpha-tocopherol, methylphosphate, citric acid, cholesterol, isocitric acid, myristic acid, arachidonic acid, and nicotinamide. Importantly, the levels of dihydrocholesterol and cholesterol were inversely associated with AOM-induced colonic ACF formation. Functional pathway and enrichment analyses indicated that diets and AOM-induced colonic ACF modulated 5 metabolic pathways: (a) citrate cycle (TCA cycle), (b) arginine biosynthesis, (c) aminoacyl-tRNA biosynthesis, (d) alanine, aspartate and glutamate metabolism, (e) glyoxylate and dicarboxylate metabolism. Conclusions Collectively, we demonstrate that AOM decreases dihydrocholesterol and cholesterol levels, and alters the composition of plasma metabolome to a greater extent in mice fed a HFD compared to the AIN. Funding Sources This work was supported by U.S. Department of Agriculture, Agricultural Research Service, research project 3062-51000-056-00D.

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