Serine, glutamate, and proline in a high-fat diet exacerbated metabolite reduction-induced memory and cognitive decline

Epidemiological studies have shown that excessive consumption of meat may cause memory loss and cognitive decline, but the underlying mechanism is unknown. Here, a high-chicken-protein diet but not a high-pork diet was found to have a markedly negative impact on the enteric nervous system and hippocampal function. Higher serine, glutamate, and proline levels in the high-chicken-protein diet inhibited the absorption capacity of amino acids, reduced the levels of neurotransmitters, and further increased hippocampal beta-secretase levels. Alzheimer's disease mouse model and cell studies confirmed that high-chicken diet-induced changes in the intestinal function further resulted in metabolic disorders with a reduction in L-serine and niacinamide in serum, accumulation of hippocampal beta-amyloid, and eventually aggravated memory and cognitive decline. Our findings highlight the importance of serine, glutamate, and proline as systemic mediators of diet-gut-brain axis homeostasis against memory and cognitive dysfunctions associated with excessive intake of chicken.