The gut microbiome has emerged as a potential intermediary in virtually every domain of human health, from metabolism to immunity to brain function. Whether it also plays a meaningful role in sleep and circadian disorders is the question addressed by a new scoping review in Sleep Medicine, which systematically mapped the available evidence across insomnia, obstructive sleep apnea, circadian misalignment, and sleep deprivation.
Livia G. Fregolente, Claudio L.A. Bassetti, and colleagues at the Sleep-Wake Epilepsy Center of Bern University Hospital screened 2,059 records from MEDLINE, Embase, and Cochrane, ultimately including 54 studies. Their analysis captures a field still in its early stages, but one that is converging on a consistent picture: sleep disruption and gut microbiome changes are linked, even if the nature and direction of that link remain unresolved.
What the evidence shows
The reviewed studies fell into three categories: 38 observational, 9 interventional, and 7 genome-wide association or Mendelian randomization analyses. Insomnia was the most frequently investigated condition (28% of studies), followed by obstructive sleep apnea (22%), circadian rhythm disruption or misalignment (19%), and sleep deprivation or short sleep duration (17%).
Across these phenotypes, the review identified several recurring patterns. Microbiome alpha diversity, a measure of species richness within an individual, was consistently altered in individuals with sleep disruption compared with controls. Taxonomic composition shifted, and several studies reported reductions in bacterial taxa known to produce short-chain fatty acids (SCFAs), metabolites that serve as key signaling molecules between the gut and the brain. Bile acid-related metabolic pathways also appeared dysregulated, and inflammatory markers correlated with both sleep measures and microbiome composition.
These patterns cut across diagnostic boundaries. Whether the primary insult was insomnia, apnea-related intermittent hypoxia, or a shift-work schedule, the microbiome showed broadly similar types of change, suggesting a shared gut response to sleep disruption rather than disorder-specific microbial signatures.
Causality: the unresolved question
The central gap the review identifies is causality. The vast majority of included studies were cross-sectional, measuring the microbiome at a single time point. Without longitudinal sampling, ideally before, during, and after sleep intervention, it is impossible to tell whether sleep disruption reshapes the gut ecosystem, whether a pre-existing dysbiosis predisposes to poor sleep, or both.
The few interventional studies that exist provide hints but no definitive answer. Some showed that treating OSA with continuous positive airway pressure partially restored microbiome composition. Others found that experimental sleep restriction altered gut microbial profiles within days. But sample sizes were small, and confounding variables such as diet, medication use, BMI, and comorbidities were inconsistently controlled.
The Mendelian randomization studies, which use genetic variants as instrumental variables to infer causal direction, offer the strongest evidence for a bidirectional relationship. Genetic predisposition to insomnia was associated with alterations in gut microbial taxa, and conversely, certain microbial traits appeared to influence sleep traits. These findings require replication in larger cohorts.
Implications
For clinicians, the review underscores that gut microbiome assessment is not yet ready for routine use in sleep medicine. Standardized protocols for sample collection, sequencing, and analysis are lacking, and no disorder-specific microbial signature has been validated. For researchers, the message is clear: the field needs prospective, multi-omics studies that track the microbiome across time, control for the major confounders, and integrate metabolomic and inflammatory data to bridge the gap between correlation and mechanism.
Limits
As a scoping review, this study maps the literature rather than pooling effect sizes. The heterogeneity of sleep phenotyping and microbiome analysis methods precludes meta-analysis, and the review’s search cutoff of February 2024 means some recent work is not captured.
Bottom line
A systematic scoping review of 54 studies confirms that sleep-wake and circadian disturbances are consistently associated with gut microbiome alterations, including reduced diversity, shifts in SCFA-producing taxa, and bile acid pathway changes. Causality remains unproven, and standardized longitudinal studies are urgently needed.
Source: Fregolente LG, Roth FN, Warncke JD, Macpherson AJ, Yilmaz B, Bassetti CLA. The gut-sleep connection: a scoping review into microbiome alterations in sleep-wake and circadian disorders. Sleep Med. 2026 Jul 10;147:109136. doi: 10.1016/j.sleep.2026.109136. PMID: 42437546.