ORIGINAL CONTRIBUTION Diverse effects of oats on cholesterol metabolism in C57BL/6 mice correlate with expression of hepatic bile acid-producing enzymes Kristina E. Andersson • Ulrika Axling • Jie Xu • Karl Swa ¨rd • Siv Ahrne ´ • Go ¨ran Molin • Cecilia Holm • Per Hellstrand Received: 14 August 2012 / Accepted: 30 November 2012 Ó Springer-Verlag Berlin Heidelberg 2012 Abstract Purpose We previously reported that two substrains of C57BL/6 mice respond differently to oats with respect to reduction in plasma cholesterol. Analysis of this difference might offer clues to mechanisms behind the cholesterol- lowering effect of oats. Here, we address the possible roles of hepatic steroid metabolism and the intestinal microbiota in this respect. Methods Female C57BL/6 mice were fed an atherogenic diet with oat bran (27 %) or control fibres for 4 weeks. Results C57BL/6 NCrl mice responded to oat bran with 19 ± 1%(P \ 0.001) lower plasma cholesterol, 40 ± 5%(P \ 0.01) higher excretion of bile acids and increased expression of the bile acid-producing hepatic enzymes CYP7A1 and CYP8B1, but none of these effects were found in C57BL/6JBomTac mice. However, on control diet, C57BL/6JBomTac had tenfold higher expression of CYP7A1 and levels of hepatic cholesterol esters than C57BL/6NCrl mice. Plasma levels of fructosamine indi- cated improved glycemic control by oat bran in C57BL/ 6NCrl but not in C57BL/6JBomTac. C57BL/6JBomTac had higher intestinal microbiota diversity, but lower num- bers of Enterobacteriaceae, Akkermansia and Bacteroides Fragilis than C57BL/6NCrl mice. Oat bran increased bacterial numbers in both substrains. Microbiota diversity was reduced by oats in C57BL/6JBomTac, but unaffected in C57BL/6NCrl. Conclusions Our data do not support a connection between altered microbiota diversity and reduced plasma cholesterol, but the bacterial composition in the intestine may influence the effects of added fibres. The cholesterol- lowering properties of oats involve increased production of bile acids via the classical pathway with up-regulation of CYP7A1 and CYP8B1. Altered cholesterol or bile acid metabolism may interfere with the potential of oats to reduce plasma cholesterol. Keywords Plasma cholesterol  Oats  Dietary fibre  CYP7A1  Microbiota  b-glucans Introduction Consumption of oats and oat b-glucan-rich food is known to reduce the total plasma and LDL cholesterol levels, and oat- based food products, therefore, attract interest for their potential to reduce the burden of cardiovascular disease on public health [1, 2]. Although the cholesterol-reducing effect of oats is well established, the exact mechanism of action remains elusive. There are also examples in the literature when oat intake does not lower the plasma cholesterol levels [3–5], and the reason for this is not known. Determination of the detailed mechanisms of action may lead to better knowledge of which properties of oats are crucial for their health effects and thereby also allows designing new food products with improved health properties. The major pathway for the elimination of cholesterol from the body is through biliary excretion, either by direct K. E. Andersson (&)  K. Swa ¨rd  P. Hellstrand Department of Experimental Medical Science, Lund University, BMC D12, 221 84 Lund, Sweden e-mail: Kristina_E.Andersson@med.lu.se U. Axling  C. Holm Department of Experimental Medical Science, Lund University, BMC C11, 221 84 Lund, Sweden J. Xu  S. Ahrne ´  G. Molin Department of Food Technology, Engineering and Nutrition, Lund University, Lund, Sweden 123 Eur J Nutr DOI 10.1007/s00394-012-0479-1