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ABSTRACTImpacts of dietary fiber on intestinal inflammation are complex, but some specific semi-purified fibers, particularly psyllium, can protect humans and rodents against colitis. Mechanisms underlying such protection are not fully understood but may involve activation of the FXR bile acid receptor. Obesity and its associated consequences, referred to as metabolic syndrome, are associated with, and promoted by, low-grade inflammation in a variety of tissues including the intestine. Hence, we examined whether psyllium might ameliorate the low-grade intestinal inflammation that occurs in diet-induced obesity and, moreover, the extent to which it might ameliorate adiposity and/or dysglycemia in this disease model. We observed that enriching a high-fat diet with psyllium provided strong protection against the low-grade gut inflammation and metabolic consequences that were otherwise induced by the obesogenic diet. Such protection was fully maintained in FXR-deficient mice, indicating that distinct mechanisms mediate psyllium’s protection against colitis and metabolic syndrome. Nor did psyllium’s protection associate with, or require, fermentation or IL−22 production, both of which are key mediators of beneficial impacts of some other dietary fibers. Psyllium’s beneficial impacts were not evident in germfree mice but were observed in Altered Schaedler Flora mice, in which psyllium modestly altered relative and absolute abundance of the small number of taxa present in these gnotobiotic mice. Thus, psyllium protects mice against diet-induced obesity/metabolic syndrome by a mechanism independent of FXR and fermentation but nonetheless requires the presence of at least a minimal microbiota.