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Future frameworks will likely need to incorporate guidance for engineered strains, synbiotics, microbial consortia, and microbiome-based therapeutics, extending the FAO/WHO principles to more complex products while maintaining their core focus on strain specificity, safety, and evidence-based health benefits (531)

These changes stimulate a variety of proteases, lipases, kinases, phosphatases, endonucleases, and free radicals, 41,42 as well as biological processes causing cell death, such as calpain activation, 43 oxidative stress, and mitochondrial impairment

These signals can activate the stress response even in the absence of external stressors, making deep sleep difficult to achieve

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