Loss of body weight in old 5xFAD mice and the alteration of gut microbiota composition

The cause of age-related body weight loss in Alzheimer's disease (AD) is unclear. We compared the differences in food intake, malabsorption, locomotor activity, and gut microbiota composition between 5xFAD mice, a useful model of AD, and wild-type (WT) mice to investigate the mechanisms underlying lower body weight in 5xFAD mice. Fifteen-month-old male 5xFAD mice and age-matched WT mice were divided into four groups: a control diet (CD) or a high-fat diet (HFD). After feeding CD or HFD for eight to nine weeks, 5xFAD mice had a significantly lower body weight than WT mice regardless of diet (p < 0.05). Additionally, the 5xFAD mice did not show a reduction in food intake compared to the WT mice regardless of diet. To evaluate malabsorption, we performed a fecal fat test. There was no obvious fecal fat in both the 5xFAD mice and WT mice. However, 5xFAD mice showed greater locomotor activity than WT mice in the Y-maze test. The comprehensive analysis of gut microbiota composition showed that 15-month-old 5xFAD mice had more Proteobacteria population and fewer Actinobacteria and Bifidobacteriales populations than WT mice. To investigate the effects of fructooligosaccharides (FOS), we administrated FOS to 15-month-old 5xFAD mice. FOS administration decreased Proteobacteria and increased Actinobacteria population, although that did not change Bifidobacteriales population. Moreover, cognitive impairment and body weight of 5xFAD mice were not changed by FOS administration. In conclusion, loss of body weight in 15-month-old 5xFAD mice might be partially derived from excess energy output by hyperactivity. Moreover, 15-month-old 5xFAD mice might have unique alteration of gut microbiota composition and the potential resistance to FOS.