Personalized pre/probiotic treatments could someday be used to support healthy sleep through stressful exam periods and menopause, a new review suggests.

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The review by scientists at the Institute for Systems Biology and the University of Surrey, ‘The human gut microbiome and sleep across adulthood: associations and therapeutic potential’, has recently been accepted for publication by Letters in Applied Microbiology, an Applied Microbiology International publication.

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The paper reports on recent findings on the gut microbiome’s associations with sleep, focusing primarily on human observational and pre/probiotic intervention trials, and is a unique contribution to the field because it discusses the findings of diverse gut-sleep studies through a lifestage lens.

Complex biological process

“Sleep is a complex biological process that both influences, and is influenced by, a wide range of factors, such as psychological stress, aging, and polypharmacy. Poor quality sleep (characterized by insufficient duration, disruptions, and/or the presence of sleep disorder) is a major public health concern, and improving sleep across the lifespan is associated with improved health outcomes, lower mortality rates, and fewer workplace and automobile accidents,” says first author, PhD student Jacob Cavon. 

“Given the intricate interplay between sleep and both biological and psychosocial factors, personalized and multifaceted approaches to improve sleep are needed.

“In our review, we highlight emerging research suggesting that the gut microbiome may be a promising biological target for supporting healthy sleep, expanding the toolkit of sleep interventions.”

Gut microbiome

A growing body of preclinical and human observational research has linked gut microbiome profiles to various sleep measures - mostly self-reported sleep. Additionally, pre/probiotic intervention trials have shown promise in improving sleep - again, mostly self-reported - particularly in individuals experiencing psychological stress, reporting sleep complaints, or living with a sleep-related condition. 

However, our mechanistic understanding of how gut microbes communicate with the brain to influence sleep remains limited, and findings differ across studies for a variety of reasons, including different population characteristics, analysis pipelines, and/or study designs, Mr Cavon said.

“Our review adds another perspective to the field by suggesting that we may want to take an age-related perspective to understand how to manipulate the gut microbiome to improve sleep across different stages of adulthood. We frame our analysis through a life stage perspective of two adult age groups (18-45 and 45+ years old), emphasizing how psychological stress in younger adults and immune changes in older adults may interact with age-related microbiome changes to influence sleep,” he said. 

Gut-sleep patterns

“In our review, we integrate findings from diverse gut-sleep studies to identify consistent gut-sleep patterns, such as associations between butyrate-producing microbes and better sleep outcomes, and highlight specific microbial taxa that warrant further investigation.” 

“For example, we discuss Alistipes, a genus associated with longevity in Chinese centenarians and Korean older adults, which is found to be depleted in individuals with obstructive sleep apnea. Interestingly, a prebiotic intervention trial in older overweight adults reported an enrichment of Alistipes alongside reduced daytime sleepiness and reduced levels of certain immune-signaling molecules. Preclinical findings also highlight Alistipes’ immune-modulating capabilities. Together, these findings suggest that Alistipes may influence sleep in an age-dependent, possibly immune-mediated, manner. 

“Finally, we highlight exciting recent technological advancements in commercial wearable devices for sleep tracking that will help make longitudinal studies on sleep more feasible.”

Little helpers

If we can identify which gut microbes influence sleep and understand the underpinning mechanisms, we can develop microbiome-based interventions to support healthy sleep, Mr Cavon said. 

“In the future, this could mean personalized pre/probiotic treatments aimed at supporting healthy sleep through periods of heavy stress (for example, exam time for students) and through periods of age-related biological changes (for example, menopause),” he predicted.

The current body of research has primarily focused on associations between specific gut microbes or overall microbiome profiles and various sleep measures, mostly self-reported sleep. However, there’s a gap in our mechanistic understanding of how the gut microbiome communicates with the brain to influence sleep, which will be important to fill in going forward, Mr Cavon said.

Bioactive metabolites

“One way gut microbes may influence sleep is through the bioactive metabolites they produce that can enter the bloodstream to affect distal organs. To gain an understanding of which microbial metabolites may be influencing sleep, future studies will need to sample additional data from participants (such as blood draws to measure blood metabolomics),” he suggested. 

“Expanding studies to include metabolic data presents significant logistical and financial challenges, but we make some actionable suggestions in our review on how to approach some of these challenges.

“Additionally, as mentioned above several times, there’s a sparsity of gut-sleep studies that capture objective measures of sleep (such as EEG, PSG, or wearable sleep trackers). Among the studies that do capture objective sleep data, sample sizes are often small, potentially limiting their statistical power to detect effects. Also, collecting and analyzing objective sleep data remains a significant challenge. 

“However, exciting recent advancements in commercial wearable sleep trackers may make data collection more cost- and labor-effective (although there will still be a need to develop standardized data analysis protocols),” Mr Cavon said.  

More sleep data

“Importantly, wearables also make longitudinal studies more feasible, which will be necessary for understanding temporal dynamics of the gut-sleep relationship, which is currently lacking in the field (most studies are cross-sectional or intervention trials with only two time points of sleep data).

“Finally, we need to expand studies to include diverse (underrepresented) populations and life stages, which will be instrumental in advancing the field towards developing equitable, personalized, microbiome-mediated interventions to improve sleep quality.”

Jacob Cavon and Melissa Basso conceptualized and wrote the review under the supervision and support of Sean M. Gibbons and Kathrin Cohen Kadosh.‘The human gut microbiome and sleep across adulthood: associations and therapeutic potential’ appears in Letters in Applied Microbiology.

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