Study: Metabolic Characteristics of Gut Microbiota and Insomnia: Evidence from a Mendelian Randomization Analysis. Image Credit: Kmpzzz / Shutterstock.com
Discover how your gut health could be the key to better sleep, as new research uncovers direct links between microbial pathways and insomnia.
A recent study published in Nutrients explores the causal associations between insomnia and metabolic pathways in the gut microbiome.
Insomnia and quality of life
Up to 30% of the global population has insomnia, particularly those of advancing age or due to the onset of illness.
Insomnia increases the risk of both physical and mental illnesses, such as depression, anxiety, diabetes, and cardiovascular disease (CVD). Insomniacs also find it harder to concentrate, work less efficiently, are more accident-prone, and accrue higher healthcare costs.
The thousands of microbial species in the human gut help digest food and produce metabolic byproducts that affect immunologic, metabolic, and neural functions. These microorganisms form part of the “gut-brain axis,” which is crucial in the sleep cycles and stress responses. In fact, general and specific gut bacteria alterations affect sleep quality.
What is MR?
MR is a valuable tool for evaluating causal relationships between genetic variables. Moreover, MR automatically adjusts for confounding factors and environmental variability that could affect the results of conventional observational studies.
For the current study, the researchers were interested in determining whether single nucleotide polymorphisms (SNPs) linked to gut microbiota pathway abundance affect insomnia risk. They also determined whether these associations would be revealed by modulating sleep-regulating metabolic pathways or gut-brain axis components.
To this end, genome-wide association study (GWAS) data linked to bacterial pathway abundance was used to identify possible associations of genetic variations with insomnia.
About the study
The current study used data from two samples obtained from the OpenGWAS and FinnGen databases, which comprise genetic and insomnia-related data, respectively. The genetic data included 205 types of gut bacterial pathway abundance.
After confirming their validity, the researchers analyzed the causal role of SNPs using multiple MR methods.
Bacterial metabolic pathways affect insomnia
Specific carbohydrates, amino acids, and nucleotides metabolized in nine types of bacteria pathways showed abundance-insomnia relationships.
Six types of pathways were responsible for increased insomnia, including carbohydrate-linked pathways like gluconeogenesis and the tricarboxylic acid (TCA) cycle and those involved in amino acid and nucleotide metabolism pathways. Increased activity in these pathways might signal metabolic dysfunction that promotes or worsens insomnia. In contrast, carbohydrate metabolic pathways, including the fermentation of hexitol to lactate, formate, ethanol, and acetate, and two other pathways, reduced the risk of insomnia, perhaps by sustaining normal sleep patterns.
Three key pathways, including gluconeogenesis, the TCA cycle, and hexitol fermentation, were directly and causally implicated in the development of insomnia. Using multivariable MR analysis, the independent role of these pathways in causing or exacerbating insomnia was established.
The results were found to be robust to sensitivity analyses. The SNPs in each type of pathway differed significantly between individuals; however, removing one SNP at a time consistently reflected the same direction of causation, although the range of the effect varied.
Conclusions
Specific metabolic pathways used by the gut microorganisms play key roles in causing insomnia. This knowledge helps understand how insomnia arises.
Abnormal glucose metabolism may leave crucial brain areas short of glucose, thus unable to drive the sleep-wake cycle. The result could be a delay in initiating or maintaining sleep.
Insulin resistance typically reduces sleep quality, while cortisol spikes during the night cause disrupted sleep and premature waking. Both of these processes are key to energy homeostasis through metabolic regulation; therefore, their dysregulation may prevent proper sleep function.
Many metabolic disorders are characterized by chronic inflammation. Inflammatory cytokines pass through the blood-brain barrier and impact sleep regulation. Thus, correcting the metabolic profile through diet, exercise, and/or medication could improve energy metabolism and lead to better sleep.
The study findings may also indicate new therapeutic targets. For example, three key pathways suggest that healthy sleep is promoted by avoiding foods rich in sugar and fat before bedtime while consuming fiber- and protein-rich foods and yogurt as a source of acidic metabolites to maintain a normal energy balance.
Future research should validate these results. The various pathways identified in the current study need further studies to investigate how their activation or inhibition alters sleep regulation through the effect on energy pathways.
The study findings may support the development of more effective and precise treatments for insomnia. These treatments may involve modulating the gut microbial composition and abundance to produce targeted alterations in the metabolic pathways.
Journal reference:
- Xie, F., Feng, Z., & Xu, B. (2024). Metabolic Characteristics of Gut Microbiota and Insomnia: Evidence from a Mendelian Randomization Analysis. Nutrients. doi:10.3390/nu16172943.