In a systematic review published in Nutrients, The researchers described gut microbiota and metabolic alterations common to metabolic syndrome (MetS) and sleep disorders.
Study: The Microbiota-Gut-Brain Axis in Metabolic Syndrome and Sleep Disorders: A Systematic Review. Image credit: Kmpzzz/Shutterstock.com
Record
One of the key mediators of the association between sleep disturbances and MetS is diet. However, scientific evidence regarding its impact on human metabolism and sleep is scarce.
Furthermore, studies have not revealed the biological mechanisms underlying the complex interplay between neuroendocrine, immunological, and metabolic pathways linking sleep disturbances to MetS.
In addition, various factors such as smoking, alcohol consumption and poor dietary habits can lead to gut dysbiosis, which, in turn, negatively affects the gut-brain axis. However, exactly how the gut microbiota affects sleep homeostasis and MetS remains unclear.
Study methodology
The researchers conducted two separate comprehensive literature searches of the Medline-Pubmed databases to review observational studies and randomized clinical trials (RCTs) published in the past ten years that investigated the microbial composition in adults with MetS and sleep disorders.
The database search returned 117 articles, of which 59 articles were selected for extensive full-text searching. The final sample set included 36 articles, 11 on sleep disorders and 25 on MetS.
The gut-brain axis
Communication between the gut and the brain is facilitated through multiple pathways. One such pathway involves the afferent vagus nerve, which innervates the gut and transmits signals to the central nervous system (CNS).
This nerve responds to various substances, including microbial neurotransmitters, hormones, fatty acids, and cytokines.
Among the different neuromodulators, acetylcholine (ACh), norepinephrine (NE) and γ-aminobutyric acid (GABA) are particularly noteworthy.
These are produced and metabolized by gut microbes, playing a key role in directly and indirectly stimulating the connection between gut afferent neurons and the CNS.
Specifically, studies have identified that Lactobacillus and Bifidobacterium spp. strains can synthesize GABA. This composition affects neurological functions, including the regulation of sleep disorders and memory.
In addition, the gut microbe Clostridium sporogenes converts tryptophan (Trp) into 5-hydroxy-tryptophan, a precursor to serotonin.
This conversion enhances the inhibitory neuromodulatory effect of L-tryptophan (Trp) by interacting with trace amine-related receptors.
In addition, the gut microbiome is involved in the neuroprotective effects of melatonin against sleep deprivation (SD)-induced cognitive impairment, as demonstrated in mouse studies.
The gut microbiome also influences the activity of immune cells, both directly and indirectly, which in turn contributes to the regulation of the circadian clock.
For example, Lactobacillus rhamnosum can stimulate regulatory T-cells both indirectly, through modulation of immune signaling through microbial cell wall components such as lipopolysaccharides (LPS), and directly, through pattern recognition receptors (PRRs).
Finally, gut microbes are known to regulate the expression of genes that regulate circadian rhythms, such as Rev-ERBA.
Host-microbial mechanisms influencing sleep disorders and the MetS
The studies included in this review demonstrated how the internal biological clock (or circadian rhythm) altered metabolic homeostasis and any changes in nutritional and metabolic status affected the circadian rhythm. Therefore, this link was reciprocal.
Furthermore, any disruption of the sensitive circadian pattern leads to internal desynchronization and organ failure, as commonly seen in sleep disorders such as sleep apnea, narcolepsy, insomnia, and circadian rhythm sleep disorders, which are categorized by their clinical manifestations.
Several controlled trials have addressed the need to establish a cause-and-effect relationship between sleep duration and gastrointestinal (GI) disorders.
They found that gut microbial neurometabolites and amino acids, such as Trp and alpha-lactalbumin (A-LAC), affected the gut-brain sleep axis.
Thus, many studies have shown that intake of Trp-rich foods, such as milk, is associated with improved sleep quality.
In an RCT, Schaafsma et al. showed that three weeks of supplementation of a dairy-based product in people with sleep disorders effectively improved their Pittsburgh Sleep Quality Index (PSQI) score and lowered their cholesterol levels.
Surprisingly, the stool samples collected at the end of the study showed an abundance Bifidobacteraceae. This gut microbe produces an active form of GABA. As such, it is a critical player in the stress/anxiety/sleep axis.
MetS is a complex of dyslipidemia, hypertension, central obesity, impaired insulin sensitivity, and low-grade systemic inflammation and is a well-recognized marker of microbial dysbiosis in MetS.
In addition, patients with MetS show a deficiency in gut microbes that produce short-chain fatty acids (SCFA).
A number of studies included in this review indicated that the metabolic impairments observed in MetS were due to a reduction in the bacterial unconjugation activity of primary bile acids.
Other studies have shown that microbe-derived metabolites called branched-chain aromatic amino acids (BCAAs), e.g. leucine, are involved in obesity-related insulin resistance through an mTOR-dependent mechanism.
A growing number of studies have also highlighted the importance of feeding timing and rhythmicity in shaping the gut microbial communities that can achieve this.
Thus, only long-term dietary interventions can permanently alter the gut microbial composition to ameliorate MetS.
In addition, many animal studies and human studies have shown that higher dietary fiber intake leads to a higher prevalence of bacterial SCFA producers in the gut, which are beneficial for glucose homeostasis and improvement of metabolic parameters in MetS.
Interestingly, this effect correlates with its enrichment Bifidobacterium observed in the case of improved sleep.
conclusions
Overall, this review highlights the importance of high-fiber diets in modulating beneficial bacteria in the gut microbiota composition of individuals with MetS and sleep disorders.
In sleep disorders, a possible common microbial signature is a lower abundance of butyrate producers (a SCFA), particularly Faecalibacterium prausnitzii, combined with a reduction of some of its members Lachnospiraceae family, like Roseburiaand an enrichment in Bacteroidetes phylum.
This pattern is similar to the observed decrease in SCFA producers in MetS. Since the MetS cohorts examined in this review were larger, more controlled, and better taxonomically defined, their microbial pattern is more consistent for further investigation.
