A new review compiles current insights into the various ways gut bacteria directly and indirectly influence sleep-wake cycles. The evidence indicates that gut microbiota dysbiosis (imbalance) both results from and contributes to sleep disturbances, which the authors warn can create vicious cycles that perpetuate poor sleep and associated health problems.
The study points to microbiota-targeted interventions in pre-, pro-, and synbiotics as a “promising frontier” to address the global burden of sleep, with potential added benefits in brain health, metabolic function, and quality of life.
Although sleep disorders affect millions worldwide, the full complexity of sleep regulation is not fully understood. Conditions ranging from chronic insomnia and sleep apnea to circadian rhythm disturbances significantly impact physical health, cognition, and emotional well-being.
Earlier research has highlighted central nervous mechanisms regulating sleep. However, the researchers in China and the US note that their “groundbreaking” review examines the often-overlooked but critical role of peripheral organs, particularly the digestive system, in modulating brain function and behavior.
“The gut microbiota is increasingly recognized as a key player in neurological and psychiatric health,” explains lead researcher Lin Lu, professor at Peking University Sixth Hospital, China. “Our review demonstrates that disruptions in gut microbiota composition are closely linked to sleep disturbances across multiple disorders.”
The researchers note that changes across multiple sleep disorders could contribute to inflammation and metabolic dysregulation, which are common in patients with sleep disorders.
They highlight that the evidence provides a “strong foundation” for developing precision probiotics, optimized prebiotics, and personalized synbiotics tailored to specific sleep disorders and individuals.
From the gut to the brain
The review published in Brain Medicine notes that research has moved beyond investigating correlations toward identifying causal relationships between the gut and sleep, demonstrating that microbial signatures can directly influence sleep physiology.
Sleep disorders like chronic insomnia, sleep apnea, and circadian rhythm disturbances significantly impact physical health, cognition, and emotional well-being.For their review, the researchers examined evidence from human clinical studies and animal models. Their findings suggest that patients with chronic insomnia exhibit decreased microbial diversity and higher concentrations of specific bacteria compared to healthy controls.
The evidence also points to similar patterns in obstructive sleep apnea, and circadian rhythm disorders exhibit distinct microbial signatures.
The article describes several biological pathways through which gut microbiota influences sleep regulation, with metabolic, neurological, and immunological interactions. Microbial metabolites play a central role. For example, short-chain fatty acids, such as butyrate, have been shown to demonstrate protective effects against sleep disruption.
Additionally, the microbiota influences the production of neurotransmitters involved in sleep regulation, including gamma-aminobutyric acid (GABA). At the same time, it is also the main production site for the hormones serotonin and melatonin, which impact the sleep-wake cycle.
Meanwhile, the review cautions that sleep disturbances commonly accompany neuropsychiatric conditions, including depression, anxiety disorders, autism spectrum disorder, and neurodegenerative diseases. The authors note that alterations in gut microbiota in these cases may contribute to the psychiatric condition and related sleep problems through shared inflammatory and neurotransmitter pathways.
Sleep-supporting biotics
As microbiota-targeted interventions to improve sleep, the review highlights the potential of pro-, pre-, and synbiotics, as well as fecal microbiota transplantation.
Multiple clinical trials across diverse populations have highlighted the promise of probiotics, with specific strains improving sleep quality, reducing cortisol levels, and enhancing sleep architecture in individuals with chronic insomnia.
Biotics are highlighted as the most suitable for widespread use in the short-term with their safety profiles, accessibility, and regulatory acceptance.The review details that probiotics like Bifidobacterium animalis subsp. lactis Probio-M8 demonstrated significant improvements in Parkinson’s disease sleep scale scores. A study on rats showed that B. animalis BB-12 enhanced sleep efficiency and diminished anxious behavior.
It also points to evidence on prebiotics suggesting that supplementation can modulate bile acid metabolism, reduce inflammation, and improve sleep metrics following circadian disruption. For example, randomized controlled trials have shown that hydrolyzed guar gum supplementation over 12 weeks significantly improves sleep inventory scores in healthy elderly individuals.
The authors note that combinations of pre- and probiotics may offer synergistic benefits. For example, clinical trials found that synbiotic formulations significantly improved sleep quality in patients with post-acute COVID-19 syndrome and other conditions characterized by sleep disturbances.
Another study found that a combination of Bifidobacterium and Lactobacillus species, along with prebiotics inulin and oligosaccharides, and postbiotics, significantly improved sleep quality in participants with sleep disturbances after eight weeks.
Fecal microbiota transplantation from healthy donors has “shown remarkable efficacy in small clinical studies,” highlight the researchers. This therapy represents a more comprehensive and dramatic approach to restoring gut microbiome balance.
Research indicates that this option can improve sleep quality scores and reduce insomnia severity in patients with insomnia who also experience other chronic diseases.
Real-world benefits
The review suggests that future research should compare microbiota-targeted solutions, their cost-effectiveness, and long-term safety data to identify the relative advantages, risks, and therapeutic relevance of these therapies. Currently, no trials have compared these solutions “head-to-head.”
The authors predict that advances in microbial sequencing and functional studies will enable the identification of key bacterial strains that specifically influence sleep and wakefulness.
The review on human clinical and animal studies notes that gut microbiota dysbiosis both results from and contributes to sleep disturbances.“Such discoveries could lead to the development of precision probiotics,” reveals the paper. “A deeper understanding of the gut-sleep axis will pave the way for innovative strategies to combat sleep disorders and improve overall health.”
For the short term, the authors suggest that probiotics are the most suitable for widespread clinical use, as these demonstrate favorable safety profiles, accessibility, and regulatory acceptance. Prebiotics hold a similar safety profile and ease of implementation, while synbiotics combine these benefits.
Meanwhile, fecal microbiota transplantation faces significant obstacles to widespread use, including donor screening requirements, infection risk, and regulatory limitations, making it more suitable for research settings.
Future research needs
Expanding research findings suggest that the gut microbiota can be a valuable biomarker for future diagnosis, prediction of treatment effectiveness, and personalized intervention.
At the same time, the review highlights challenges to advancing clinical applications. The authors suggest that future research address these challenges and develop a clear translational pathway:
Prioritizing interventional trials for disorders with the strongest mechanistic links, like chronic insomnia.
Standardizing key biomarkers across studies, such as microbial sequencing data, sleep metrics, and relevant metabolic profiles.
Harmonizing methodologies from DNA extraction to sleep assessment tools to enable valid cross-study comparisons.
“While significant progress has been made, important challenges remain,” concludes Lu. “We need larger, well-controlled clinical trials with standardized methodologies to validate therapeutic approaches and understand individual response variability.”
“Harmonizing techniques across studies, from sample collection and DNA extraction to sleep assessment tools, will enable meaningful cross-study comparisons and accelerate translation to clinical practice.”
