Synergistic effect of n-3 PUFA and probiotic supplementation on bone loss induced by chronic mild stress through the brain–gut–bone axis

This study was to investigate the synergistic effect of n-3 polyunsaturated fatty acids (PUFA) and probiotics on depression-induced bone loss. Rats were fed with a diet composed of 0% or 1% n-3 PUFA and live or dead probiotics, and underwent chronic mild stress. N-3 PUFA with live or dead probiotics enhanced bone mass, calcium, and osteoprotegerin and decreased amino-terminal cross-linked telopeptide of type 1 collagen, receptor activator of nuclear factor kappa-Β ligand, and cytokines. N-3 PUFA and probiotics increased brain serotonin and modulated the hypothalamic–pituitary–adrenal axis, thereby decreasing the bone expression of beta 2 adrenergic receptor and activating transcription factor 4 and increasing runt-related factor 2. N-3 PUFA and probiotics decreased gut serotonin, which downregulated the bone expression of 5-hydroxytryptamine receptor 1B and increased cyclic adenosine monophosphate. This study showed the synergistic bone-protective effects of n-3 PUFA and probiotics through the brain–gut–bone axis.