A review published in Nutrients examined existing preclinical and limited clinical evidence showing that intermittent fasting (IF) may help reduce the toxic protein burden, support synaptic function, and rehabilitate glial and immune homeostasis across models of various neurodegenerative disorders.
Intermittent fasting and the gut-brain axis
Research has linked IF to higher levels of bacteria known to produce beneficial metabolites and regulate immune responses. Among these metabolites, short-chain fatty acids (SCFAs) are crucial signalling molecules in the gut-brain axis (GBA), and existing evidence points to the role of IF in increasing SCFA-producing bacteria, such as Eubacterium rectale, Roseburia spp., and Anaerostipes spp. Preclinical studies have associated this with increased hippocampal synaptic density and reduced tau protein phosphorylation in animal models of Alzheimer’s Disease (AD).
IF upregulates microbial gene expression, particularly enhancing the growth of butyrate-producing taxa. It also modifies bile acid metabolism and modulates tryptophan pathways, thereby improving the production of neuromodulatory metabolites, e.g., serotonin and kynurenine. IF has been associated with a decline in circulating monocytes, which are extremely important in the body’s inflammatory response.
Chronic low-grade inflammation and inflammaging from the gut are increasingly recognized as key factors in neurodegeneration. Intestinal permeability, also known as "leaky gut," allows microbial endotoxins to enter the systemic circulation, triggering immune responses and producing proinflammatory cytokines. IF can enhance SCFA-producing microbes, improving epithelial integrity and reducing endotoxin exposure.
