Study explores the mediatory role of gut microbiota in metabolic syndrome and sleep disorders

In a systematic review published in Nutrients, 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

Background

One of the key mediators of the association between sleep disorders and MetS is diet. Yet, scientific evidence on its impact on human metabolism and sleep is scarce.

Moreover, studies have not unveiled the biological mechanisms governing the intricate crosstalk between neuroendocrine, immune, and metabolic pathways that connect sleep disorders to MetS.

Furthermore, several factors, such as smoking, alcohol consumption, and poor dietary habits, may lead to gut dysbiosis, which, in turn, adversely affects the gut–brain axis. However, how precisely the gut microbiota affects sleep homeostasis and MetS remains unclear.

Study methodology

Researchers conducted two separate thorough literature searches in the Medline-Pubmed databases to review observational studies and randomized clinical trials (RCTs) published in the last ten years investigating the microbial composition in adults with MetS and sleep disorders. 

The database search returned 117 articles, of which they selected 59 articles for extensive full-text search. The final sample set comprised 36 articles, 11 for sleep disorders and 25 for MetS.

The gut-brain axis

The 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 relays signals to the central nervous system (CNS).

This nerve is responsive to various substances, such as microbial neurotransmitters, hormones, fatty acids, and cytokines.

Among the diverse neuromodulators, acetylcholine (ACh), norepinephrine (NE), and γ-aminobutyric acid (GABA) are particularly notable.

These are produced and metabolized by gut microbes, playing a crucial role in directly and indirectly stimulating the connection between the gut’s afferent neurons and the CNS.

Specifically, studies have identified that Lactobacillus and Bifidobacterium spp. strains can synthesize GABA. This synthesis impacts neurological functions, including the modulation of sleep disorders and memory.

Additionally, the gut microbe Clostridium sporogenes converts tryptophan (Trp) into 5-hydroxy-tryptophan, a precursor of serotonin.

This conversion enhances the inhibitory neuroregulatory effect of L-tryptophan (Trp) by interacting with trace amine-associated receptors.

Moreover, the gut microbiome is involved in the neuroprotective effects of melatonin against cognitive impairment caused by sleep deprivation (SD), as demonstrated in mouse studies.

The gut microbiome also influences immune cell activity, both directly and indirectly, which in turn contributes to regulating the circadian clock.

For example, Lactobacillus rhamnosum can stimulate regulatory T-cells both indirectly, through the modulation of immune signaling via microbial cell wall components like lipopolysaccharides (LPS), and directly, through pattern-recognition receptors (PRRs).

Lastly, gut microbes are known to modulate the expression of genes that regulate circadian rhythms, such as Rev-ERBA.

Host-microbial mechanisms influencing sleep disorders and 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 statuses affected the circadian rhythm; thus, this link was reciprocal. 

Moreover, any perturbation to the delicate circadian pattern leads to internal desynchrony and organ failure, as commonly observed in sleep disorders, such as sleep apnea, narcolepsy, insomnia, and circadian rhythm sleep disorders, categorized based on their clinical manifestations.

Several controlled trials addressed the need to establish a cause-and-effect association 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 sleepgut–brain axis.

Thus, many studies have shown that intake of Trp-rich foods, such as milk, is linked to improved sleep quality.

In an RCT, Schaafsma et al. showed that three weeks of supplementation of a dairy-based product in subjects with sleep disorders effectively ameliorated their Pittsburgh Sleep Quality Index (PSQI) score and reduced their cholesterol levels.

Intriguingly, fecal samples collected at the end of the study showed an abundance of Bifidobacteraceae. This gut microbe produces an active form of GABA; thus, it is a crucial player in the stress/anxiety/sleep axis.

MetS is an ensemble of dyslipidemia, hypertension, central obesity, disrupted insulin sensitivity, and low-grade systemic inflammation and is a well-recognized marker of microbial dysbiosis in MetS.

In addition, MetS patients exhibit a deficiency in short-chain fatty acid (SCFA) producing gut microbes. 

Some studies included in this review showed that metabolic impairments observed in MetS were due to a decline in bacterial deconjugation activity of primary bile acids.

Other studies showed that microbial-derived metabolites called branched-chain aromatic amino acids (BCAAs), e.g., leucine, were involved in obesity-associated insulin resistance via an mTOR-dependent mechanism.

More and more studies have also pointed out the importance of feeding time and rhythmicity in shaping gut microbiota communities that can achieve this.

Thus, only long-term dietary interventions may permanently alter the gut microbial composition to ameliorate MetS.

Moreover, multiple animal studies and studies with human subjects demonstrated that higher ingested dietary fiber intake leads to a higher prevalence of bacterial SCFA producers in the gut, which are beneficial for glucose homeostasis and ameliorating metabolic parameters in MetS.

Interestingly, this effect correlates with the enrichment of Bifidobacterium observed in the case of sleep improvements. 

Conclusions

Overall, this review highlights the importance of diets rich in fiber to modulate the beneficial bacteria in the gut microbiota composition of subjects with MetS and sleep disorders.

In sleep disorders, a potential common microbial signature is the lower abundances of butyrate (a SCFA) producers, especially Faecalibacterium prausnitzii, coupled with a reduction in some members of the Lachnospiraceae family, like Roseburia, and an enrichment in the Bacteroidetes phylum. 

This pattern is similar to the observed decrease in SCFA producers in MetS. Since MetS cohorts examined in this review were larger, more controlled, and better taxonomically defined, their microbial pattern is more consistent for further investigation.