Dietary non-digestible carbohydrates are perceived to improve health via gut microbiota-dependent generation of products such as short-chain fatty acids (SCFA). In addition, SCFA are also precursors for lipid and cholesterol synthesis potentially resulting in unwanted effects on lipid metabolism. Inulin is a widely used model prebiotic dietary fiber. Inconsistent reports on the effects of inulin on cholesterol homeostasis have emerged in humans and preclinical models. To clarify this issue, the present study aimed to provide an in-depth characterization of the effects of short-chain (sc)- and long-chain (lc)- inulin on cholesterol synthesis, absorption and elimination in mice. Feeding wildtype C57BL/6J mice diets supplemented with 10% (w/w) of either sc- or lc-inulin for two weeks resulted in approximately 2.5-fold higher fecal SCFA levels (P < 0.01) compared with controls, but had no significant effects on plasma and liver lipids. Subtle shifts in fecal and plasma bile acid species were detected with beta-muricholic acid increasing significantly in plasma of the inulin fed groups (1.7-fold, P < 0.05). However, neither sc-inulin nor lc-inulin affected intestinal cholesterol absorption, mass fecal cholesterol excretion or trans-intestinal cholesterol excretion (TICE). Combined, our data demonstrate that sc- and lc-inulin have no adverse effects on cholesterol metabolism in mice despite increased generation of SCFA.
These data demonstrate that the absence of the intestinal microbiota stimulates RCT >2-fold. Thereby, our results support the importance of intestinal bacteria for metabolic regulation and indicate that specific targeting of the microbiota bears therapeutic potential to prevent and treat cardiovascular disease.
Scope The gut microbiota might critically modify metabolic disease development. Dietary fibers such as galacto‐oligosaccharides (GOS) presumably stimulate bacteria beneficial for metabolic health. This study assesses the impact of GOS on obesity, glucose, and lipid metabolism. Methods and results Following Western‐type diet feeding (C57BL/6 mice) with or without β‐GOS (7% w/w, 15 weeks), body composition, glucose and insulin tolerance, lipid profiles, fat kinetics and microbiota composition are analyzed. GOS reduces body weight gain ( p < 0.01), accumulation of epididymal ( p < 0.05), perirenal ( p < 0.01) fat, and insulin resistance ( p < 0.01). GOS‐fed mice have lower plasma cholesterol ( p < 0.05), mainly within low‐density lipoproteins, lower intestinal fat absorption ( p < 0.01), more fecal neutral sterol excretion ( p < 0.05) and higher intestinal GLP‐1 expression ( p < 0.01). Fecal bile acid excretion is lower ( p < 0.01) in GOS‐fed mice with significant compositional differences, namely decreased cholic, α‐muricholic, and deoxycholic acid excretion, whereas hyodeoxycholic acid increased. Substantial changes in microbiota composition, conceivably beneficial for metabolic health, occurred upon GOS feeding. Conclusion GOS supplementation to a Western‐type diet improves body weight gain, dyslipidemia, and insulin sensitivity, supporting a therapeutic potential of GOS for individuals at risk of developing metabolic syndrome.
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