Differential effects of the soluble fiber inulin in reducing adiposity and altering gut microbiome in aging mice

Inulin, a soluble dietary fiber, is thought to exert multiple beneficiary effects through promoting growth of bacteria that metabolize the fiber to short-chain fatty acids (SCFAs); however, the effect and efficacy of inulin in aging subjects is unknown. This study aims to systematically evaluate the capacity of SCFAs production and host response in mice of different ages. Male C57BL/6J mice across young (5 months), middle (11 months) and old (26 months) age were subjected to a control diet for 2 weeks, followed by 6 weeks of inulin-containing diet. Inulin-induced increase in fecal butyric acid levels was most prominent in middle-age group compared to other age groups. In addition, inulin-induced increase in fecal propionic acids showed age-dependent decline. Interestingly, the SCFA-producing Roseburia was most abundantly and persistently increased in the middle-age group. Furthermore, inulin intake significantly reduced Firmicutes to Bacteroidetes ratio, and several dysbiotic bacteria associated with pro-inflammatory state. Concomitantly, circulating levels of CXCL1, a chemoattractant for neutrophils, was reduced by inulin intake. Inulin decreased fat mass in all age groups, with middle-aged mice being most responsive to fat-reducing effects of inulin. Moreover, inulin significantly increased energy expenditure and voluntary wheel running in middle-aged mice, but not in old mice. Overall, our data suggest that the efficacy of inulin in altering the microbiome and SCFA production, and the subsequent metabolic response was diminished in old mice, and highlight the importance of including age as a variable in studies determining host-microbe response to diets.