Understanding the Role of Oral Melatonin in Gut Microbiota and Metabolic Regulation
Oral melatonin has emerged as a significant player in regulating metabolic processes, influencing the gut microbiota and its communication with host tissues. Recent studies suggest that microbial-derived metabolites could offer potential therapies for disrupting circadian rhythms and related metabolic syndromes.
Impact of Gut Microbiota on Circadian Rhythms and Fat Metabolism
The gut microbiome has been shown to be sensitive to both circadian rhythms and host fat metabolism. Research highlights that oral melatonin benefits various physiological functions; however, its effects on the gut microbiota-host communication remain less understood. Notably, Angiopoietin-like protein 4 (ANGPTL4) plays a crucial role in regulating systemic lipid metabolism. Investigations reveal that oral melatonin can enhance lipid metabolism abnormalities in the ileum and epididymal white adipose tissue (eWAT) through gut microbiota interactions and ileal ANGPTL4 modulation.
Mechanisms of Action
Oral melatonin is shown to reduce lipopolysaccharide (LPS) production from Escherichia coli. This action alleviates the transcriptional inhibition of ANGPTL4 mediated by the ileal TLR4/IL-22/STAT3 signaling pathway, which consequently improves lipid intake in the ileum and reduces fat accumulation in eWAT. Such findings underscore the innovative role of oral melatonin as a modulator in host distal tissue functions.
The Public Health Threat of Lipid Metabolism Disorders
Lipid metabolism disorders pose a significant threat to public health, contributing to obesity—a multi-organ metabolic disease. Evidence suggests that excessive fat intake is a contributing factor to obesity. Multiple organs, notably the gut and adipose tissues, are heavily involved in lipid transport and storage. Previous studies emphasized that maintaining lipid homeostasis is vital for protecting individuals from such metabolic disruptions.
Alterations in Gut Environment and Microbiota Patterns
In obese individuals, modifications occur not only within the gut's cellular environment—such as increased permeability due to low expression of tight junction proteins—but also in the overall microbial composition of the gut. Recent investigations have revealed a close relationship between the gut microbiota and host energy metabolism, highlighting its potential role as a significant modulator in these metabolic processes.
Influence of Diet on Gut Microbiota Composition
Research indicates that the composition of the gut microbiota is subject to change with dietary habits, directly impacting host metabolism, including nutrient absorption and pathogen prevention. Advances in bacterial genomic sequencing over the past decade have facilitated a deeper understanding of how physiological activities in hosts relate to variations in gut microbiota.
Discrepancies in Microbial Studies
A perplexing issue arises from the conflicting results observed in different studies regarding gut microbiota composition in humans and animal models. It is commonly noted that two dominant phyla, Bacteroidetes and Firmicutes, are significantly affected by intermittent fasting, yet contradictory findings regarding their respective effects persist. Consequently, research increasingly focuses on specific components or rare strains within the gut microbiota.
Circadian Rhythm Disruption and Metabolic Syndrome
Chronodisruption has also been recognized as a key factor in the onset of obesity and related metabolic syndromes. In mammals, circadian clocks synchronize various metabolic activities to ensure optimal balance between anabolism and catabolism in different organs. Unlike the central clock located in the suprachiasmatic nucleus of the hypothalamus, peripheral clocks within organs such as the gut and adipose tissue serve as rhythmic oscillators driving gene expression.
Interplay Between Gut Microbiota and Circadian Clocks
Given the strong correlation between symbionts and the host, it is hypothesized that overlapping or interacting effects may trigger significant metabolic changes. Therefore, the interaction between gut microbiota and peripheral circadian clocks could play a vital role in regulating host obesity.
Key Findings and Therapeutic Implications
In conclusion, findings indicate that: (1) the gut microbiota in JL mice is associated with weight control mediated by oral melatonin; (2) ANGPTL4 may play a significant role in transferring information from gut microbes to host adipose tissues; (3) microbial LPS activates the TLR4/STAT3 pathway, inhibiting ileal ANGPTL4 transcription and promoting high expression of NFIL3; (4) oral melatonin can lower microbial-origin LPS levels by suppressing LpxC expression. These data suggest that oral melatonin-induced alterations in the gut microbiota could represent a promising therapeutic approach to restoring ileal ANGPTL4 levels and addressing lipid metabolism disorders triggered by circadian disruption.