Dietary lactoferrin has differential effects on gut microbiota in young versus middle-aged APPswe/PS1dE9 transgenic mice but no effects on cognitive function

BACKGROUND: Existing evidence suggest that lactoferrin might be beneficial for Alzheimer’s disease, while precise mechanisms are not fully elucidated. OBJECTIVE: To determine the effects of lactoferrin intervention on cognitive function from APPswe/PS1dE9 (APP/PS1) mice, and potential mechanisms involved. DESIGN: Both the young and middle-aged male APP/PS1 mice were divided into the control and lactoferrin intervention groups with 16 weeks’ intervention. RESULTS: Lactoferrin had no effects on cognitive function for both the young and middle-aged mice, and no key markers involved in Aβ, tau pathology, neuro-inflammation and synaptic plasticity were altered after lactoferrin intervention. With regards to gut microbiota profiles, in the young APP/PS1 mice, lactoferrin elevated the α diversity index including ACE and Chao 1, and reduced the relative abundance of the genera Bacteroides and Alistipes and elevated Oscillibacter; in addition, Oscillibacter, Anaerotruncus, EF096579_g, EU454405_g, Mollicutes_RF39, EU474361_g, EU774448_g, and EF096976_g were specifically abundant via linear discriminant analysis with effect size (LEfSe) analysis. In the middle-aged APP/PS1 mice, the relative abundance of the phylum Proteobacteria, as well as the genera Oscillospira, Coprococcus, and Ruminococcus was significantly reduced post lactoferrin; additionally, S24_7, Bacteroidia, Bacteroidetes, and Methylobacterium were specific via LEfSe analysis in the lactoferrin group. CONCLUSIONS: Dietary lactoferrin might be beneficial for gut microbiota homeostasis although it might have no effects on cognition.