From alpha diversity to zeitgebers: Functional implications and potential mechanisms linking the gut microbiome to...

The bidirectional relationship between sleep physiology and the gut microbiome is mediated by overlapping neuroendocrine, immune, and metabolic pathways, though mechanistic evidence, particularly in humans, remains limited. This scoping review, the second in a two-part series, synthesizes preclinical and translational research examining not only gut microbial composition but also biomarkers reflecting host metabolic or functional responses to sleep and circadian disruption. We reviewed 74 preclinical rodent studies and 65 human studies that assessed sleep, gut microbiome outcomes, and at least one biomarker related to hormones, metabolites, neurotransmitters, or inflammation. Across studies, consistent links emerged between sleep and circadian disruption and changes in host homeostasis through microbiome-mediated mechanisms. These include activation of the hypothalamic-pituitary-adrenal axis, altered bile acid metabolism, inflammation-related microbial shifts, and disrupted tryptophan pathways. Together, these findings suggest that altered sleep influences metabolic and immune function via gut microbial signaling pathways. We highlight directions for future mechanistic research, particularly in translational models, to clarify causal pathways and support microbiome-informed strategies for mitigating the health consequences of sleep and circadian disruption.