Obesity is an established risk factor for many diseases including intestinal cancer. One of the responsible mechanisms is the chronic inflammation driven by obesity. However, it remains to be defined whether diet-induced obesity exacerbates the intestinal inflammatory status by cytokines produced in adipose tissue or the high fat diet first alters the gut microbiota and then drives intestinal inflammation. To address this question, we fed C57BL/6 mice with a high fat diet (HF, 60%) and sacrificed them sequentially after 8, 12, and 16 weeks, and then compositions of gut microbiota and expressions of antimicrobial peptides were determined. The compositions of gut microbiota were altered at 8 wk HF feeding, followed with reduced Paneth antimicrobial peptides lysozyme and Reg IIIγ after 12 and 16 wk HF feeding (p < 0.05), whereas elevations of circulating inflammatory cytokines IFNγ and TNF-α were observed until feeding a HF diet for 16 weeks (p < 0.05). These results indicated that high fat diet may stimulate intestinal inflammation via altering gut microbiota, and it occurs prior to the potential influence by circulating inflammatory cytokines. These findings emphasized the importance of microbiota, in addition to adipose tissue per se, in driving intestinal inflammation, which may thereafter promote intestinal tumorigenesis.

Gut dysbiosis induced by high fat diet (HF) or obesity is a predisposing factor to develop diverse inflammatory diseases. Polyphenols and fibers, often eaten together, have been reported to have prebiotic actions, but their health promoting benefits still need to be further characterized and defined. This study attempted to understand how polyphenol rutin and polysaccharide inulin influence intestinal health in mouse model fed a HF (60 kcal%) diet. A total of 48 C57BL/6J mice were divided into four groups fed with a low fat (10% kcal%) control diet (LC), a high fat control diet (HC), a high-fat diet supplemented with rutin (HR), or a high-fat diet supplemented rutin and inulin (HRI) for 20 weeks. Rutin supplementation reduced the HF diet-induced increase of Firmicutes/Bacteroidetes (F/B) ratio, Deferribacteraceae population and plasma lipopolysaccharide (LPS) (p < 0.05); ameliorated inflammation as indicated by the decreased circulating inflammatory cytokines (p < 0.05) and the reduced expressions of intestinal inflammatory mediators (p < 0.05); and attenuated the endoplasmic reticulum (ER) stress in Paneth cells as indicated by the decreased expressions of the ER markers (p < 0.05). Compared to the rutin supplementation alone, the co-administration of rutin with inulin improved the utilization of rutin as indicated by its decreased excretion, suppressed a number of harmful bacteria including Deferribacteraceae and Desulfovibrionaceae (p < 0.05), and further reduced the expression of the key inflammatory cytokine TNF-α and increased the production of butyrate, despite the supplementation of inulin reversed the decrease of body weight induced by rutin supplementation due to an increased food intake. Taken together, our data demonstrated that rutin supplementation ameliorated the inflammatory status and ER stress in Paneth cells under a HF-induced obese state, and its co-administration with inulin further mitigated the inflammatory status, indicating the potential to combine polyphenol rutin and the polysaccharide inulin as a dietary strategy to ameliorate gut dysbiosis, to improve inflammatory status and thereby to reduce medical disorders associated with HF-induced obesity.

The increasing worldwide incidence of colon cancer has been linked to obesity and consumption of a high-fat Western diet. To test the hypothesis that a high-fat diet (HFD) promotes colonic aberrant crypt (AC) formation in a manner associated with gut bacterial dysbiosis, we examined the susceptibility to azoxymethane (AOM)-induced colonic AC and microbiome composition in C57/BL6 mice fed a modified AIN93G diet (AIN, 16% fat, energy) or an HFD (45% fat, energy) for 14 weeks. Mice receiving the HFD exhibited increased plasma leptin, body weight, body fat composition and inflammatory cell infiltration in the ileum compared with those in the AIN group. Consistent with the gut inflammatory phenotype, we observed an increase in colonic AC, plasma interleukin-6, tumor necrosis factor-α, monocyte chemoattractant protein-1 and inducible nitric oxide synthase in the ileum of the HFD-AOM group compared with the AIN-AOM group. Although the HFD and AIN groups did not differ in bacterial species number, the HFD and AIN diets resulted in different bacterial community structures in the colon. The abundance of certain short-chain fatty acid (SCFA) producing bacteria (e.g., Barnesiella) and fecal SCFA (e.g., acetic acid) content were lower in the HFD-AOM group compared with the AIN and AIN-AOM groups. Furthermore, we identified a high abundance of Anaeroplasma bacteria, an opportunistic pathogen in the HFD-AOM group. Collectively, we demonstrate that an HFD promotes AC formation concurrent with an increase of opportunistic pathogenic bacteria in the colon of C57BL/6 mice.