Effect of the prebiotic fiber inulin on cholesterol metabolism in wildtype mice

Abstract

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.

Inulin Supplementation Disturbs Hepatic Cholesterol and Bile Acid Metabolism Independent from Housing Temperature

“…Further, they noted that inulin caused bilirubinemia and liver inflammation. In line with previous observations by other groups [ 21 , 23 , 24 ], they also detected alterations in hepatic bile acid metabolism and serum bile acid levels after long-term inulin supplementation. While inulin-induced cancer formation was partly diminished after depletion of the gut bacteria by treatment with the antibiotic compound vancomycin, the inulin-dependent alterations in bile acid metabolism and associated cholemia were unaffected [ 25 ].…”

“…There have been conflicting reports about the impact of inulin supplementation on systemic cholesterol levels and cholesterol metabolism [ 6 , 23 ], and most importantly, studies investigating the combined effect of inulin supplementation and BAT activation have not been carried out so far. To address these questions, we measured plasma lipid levels in the warm and cold housed CD- and ICD-fed mice.…”

“…Still, despite no observed differences in body weight, we were able to show that already short-term inulin supplementation dramatically reduced plasma cholesterol levels. Interestingly, while Trautwein et al saw similar effects in hamsters [ 6 ], Hoving et al and Mistry et al reported unaltered plasma cholesterol levels in mice supplemented with inulin [ 20 , 23 , 24 ]. Of note, we found that these reductions were not caused by increased hepatobiliary cholesterol excretion or decreased intestinal cholesterol uptake, as indicated by hepatic gene expression and reduced fecal cholesterol levels.…”

Dysregulated bile acid receptor-mediated signaling and IL-17A induction are implicated in diet-associated hepatic health and cognitive function

“…Inulin is a nondigestible fiber present in a wide variety of fruits and vegetables. It is commonly used as a dietary supplement for weight loss and lowering serum lipids [ 15 ]. Through gut microbial fermentation, inulin generates SCFAs that have health benefits [ 16 ].…”

Dysregulated Bile Acid Receptor-mediated Signaling and IL-17A Induction are Implicated in Diet-associated Hepatic Health and Cognitive Function

“…Inulin is a nondigestible ber present in a wide variety of fruits and vegetables. It is commonly used as a dietary supplement for weight loss and lowering serum lipids [15]. Through gut microbial fermentation, inulin generates SCFAs that have health bene ts [16].…”