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Meanwhile, the GM and its metabolites modulate mineral absorption, the RANK/RANKL/OPG signaling pathway, and systemic inflammation, thereby linking the “gut–bone axis” and the “GBA.” As a result, IBD, osteoporosis, osteoarthritis, depression, anxiety, and cognitive impairment often present with substantial comorbidity

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Similarly, hypercholesterolemia can disrupt circadian rhythms 228 , exponentially increasing the risk of atherosclerosis 229 , leading to arterial stiffening and increased systemic inflammation, both of which affect BBB and glymphatic function 230,231