The Janus Face of Cereals: Wheat‐Derived Prebiotics Counteract the Detrimental Effect of Gluten on Metabolic Homeostasis in Mice Fed a High‐Fat/High‐Sucrose Diet

SCOPE: Cereals are important sources of carbohydrates, but also contain nutrients that could impact adiposity. The contribution of gluten to obesity and the effects of prebiotics—arabinoxylo‐oligosaccharides (AXOS) and fructo‐oligosaccharides (FOS)—that can be extracted from gluten‐containing cereals are analyzed. METHODS AND RESULTS: Mice are fed a control diet, Western diet (WD, consisting of high fat/high sucrose), or WD with 5% gluten. Prebiotics are tested in the WD with gluten. Gluten does not increase body weight and has a minor effect on ileal inflammation. Gluten decreases the expression of browning markers in the fat and increases the triglycerides synthesis in the muscle. AXOS decreases body weight and adiposity in fat pads muscle and liver. AXOS promotes gluten cleavage by the induction of prolyl endopeptidase that is translated into a reduction of gluten immunogenic peptides. Gluten has minor effects on cecal microbiota composition, whereas prebiotics increased Bifidobacterium, Butyricicoccus, Prevotella, and Parasutterella, which are all negatively correlated to the cecal content of gluten peptides. CONCLUSION: While gluten may affect metabolic homeostasis, these effects are lessened when gluten is consumed along with cereal‐derived fibers. If confirmed in humans, the authors bring new arguments to eat fiber‐rich cereals to promote a healthy diet.