Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/ Prevotella in Diet-Induced Obese Mice Audrey M. Neyrinck 1 , Sam Possemiers 2 , Ce ´ line Druart 1 , Tom Van de Wiele 2 , Fabienne De Backer 1 , Patrice D. Cani 1 , Yvan Larondelle 3 , Nathalie M. Delzenne 1 * 1 Metabolism and Nutrition Research Group, Louvain Drug Research Institute, Universite ´ catholique de Louvain, Brussels, Belgium, 2 Laboratory of Microbial Ecology and Technology, Ghent University, Ghent, Belgium, 3 Institut des Sciences de la Vie, Universite ´ catholique de Louvain, Louvain-la-Neuve, Belgium Abstract Background: Alterations in the composition of gut microbiota - known as dysbiosis - has been proposed to contribute to the development of obesity, thereby supporting the potential interest of nutrients targeting the gut with beneficial effect for host adiposity. We test the ability of a specific concentrate of water-extractable high molecular weight arabinoxylans (AX) from wheat to modulate both the gut microbiota and lipid metabolism in high-fat (HF) diet-induced obese mice. Methodology/Principal Findings: Mice were fed either a control diet (CT) or a HF diet, or a HF diet supplemented with AX (10% w/w) during 4 weeks. AX supplementation restored the number of bacteria that were decreased upon HF feeding, i.e. Bacteroides-Prevotella spp. and Roseburia spp. Importantly, AX treatment markedly increased caecal bifidobacteria content, in particular Bifidobacterium animalis lactis. This effect was accompanied by improvement of gut barrier function and by a lower circulating inflammatory marker. Interestingly, rumenic acid (C18:2 c9,t11) was increased in white adipose tissue due to AX treatment, suggesting the influence of gut bacterial metabolism on host tissue. In parallel, AX treatment decreased adipocyte size and HF diet-induced expression of genes mediating differentiation, fatty acid uptake, fatty acid oxidation and inflammation, and decreased a key lipogenic enzyme activity in the subcutaneous adipose tissue. Furthermore, AX treatment significantly decreased HF-induced adiposity, body weight gain, serum and hepatic cholesterol accumulation and insulin resistance. Correlation analysis reveals that Roseburia spp. and Bacteroides/Prevotella levels inversely correlate with these host metabolic parameters. Conclusions/Significance: Supplementation of a concentrate of water-extractable high molecular weight AX in the diet counteracted HF-induced gut dysbiosis together with an improvement of obesity and lipid-lowering effects. We postulate that hypocholesterolemic, anti-inflammatory and anti-obesity effects are related to changes in gut microbiota. These data support a role for wheat AX as interesting nutrients with prebiotic properties related to obesity prevention. Citation: Neyrinck AM, Possemiers S, Druart C, Van de Wiele T, De Backer F, et al. (2011) Prebiotic Effects of Wheat Arabinoxylan Related to the Increase in Bifidobacteria, Roseburia and Bacteroides/Prevotella in Diet-Induced Obese Mice. PLoS ONE 6(6): e20944. doi:10.1371/journal.pone.0020944 Editor: Lorraine Brennan, University College Dublin, Ireland Received December 8, 2010; Accepted May 16, 2011; Published June 9, 2011 Copyright: ß 2011 Neyrinck et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: This work supported by a grant from the Walloon Region (General Directory of Agriculture, convention D31-1107, http://agriculture.wallonie.be). PDC is a Research Associate from the Fonds de la Recherche Scientifique (FRS-FNRS) Belgium (http://www.frs-fnrs.be/). SP and TVDW are Postdoctoral Researchers from the Research Foundation - Flanders (Fonds voor Wetenschappelijk Onderzoek [FWO] - Vlaanderen, http://www.fwo.be/). CD benefits from a Danone Institute grant (http://www.danoneinstitute.be/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. * E-mail: nathalie.delzenne@uclouvain.be Introduction Recent studies demonstrated that diet-induced obesity was linked to changes in the gut microbial ecology, resulting in an increased capacity of the distal gut microbiota to promote host adiposity [1,2]. We have previously shown that inulin-type fructans, non-digestible carbohydrates obtained from chicory root, restore the drop of bifidobacteria numbers occurring in the caeco- colon of high fat/carbohydrate-free diet-fed mice and thereby improves metabolic alterations associated with obesity, including dyslipidemia, impaired gut permeability, endotoxemia, inflamma- tion and diabetes [3–6]. Inulin-type fructans are typically studied as they were the first compounds to respond to the prebiotic concept, defined as the selective stimulation of growth and/or activity of one or a limited number of microbial genus(era)/species in the gut microbiota that confer(s) health benefits to the host [7]. Other non-digestible/fermented carbohydrates, which are gradu- ally fermented throughout the colon and which can be applied in different food matrices, may be valuable alternative substrates to test for their health effects related to their influence on gut microbiota composition. AX are the most important non-digestible carbohydrates pre- sent in wheat. They represent 50% of dietary fibers and are mostly present in the bran and aleurone fractions [8]. AX are selectively degraded in the colon by intestinal bacteria possessing AX- degrading enzymes such as xylanases and arabinofuranosidases PLoS ONE | www.plosone.org 1 June 2011 | Volume 6 | Issue 6 | e20944