The Microbiome as a Circadian Coordinator of Metabolism

Alvarez, Yelina; Glotfelty, Lila G.; Blank, Niklas; Dohnalová, Lenka; Thaiss, Christoph A.

doi:10.1210/endocr/bqaa059

Cited by 30 publications

(36 citation statements)

References 96 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…During the dark phase, direct GABAergic inhibitory signals from the SCN to the PVN inhibit the PVN to pineal gland projections [118,240]. Rhythmicity in melatonin provides essential regulatory control in metabolism; when melatonin synthesis is abolished by pinealectomy, glucose tolerance is impaired and blood glucose rhythmicity is completely lost under ad libitum feeding conditions [241,242]. Thus, the melatonin-mediated regulation of plasma glucose levels is controlled by a delicate balance of glutamatergic and GABAergic pre-autonomic hypothalamic inputs.…”

Section: Melatoninmentioning

confidence: 99%

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

View full text Add to dashboard Cite

The nearly ubiquitous expression of endogenous 24 h oscillations known as circadian rhythms regulate the timing of physiological functions in the body. These intrinsic rhythms are sensitive to external cues, known as zeitgebers, which entrain the internal biological processes to the daily environmental changes in light, temperature, and food availability. Light directly entrains the master clock, the suprachiasmatic nucleus (SCN) which lies in the hypothalamus of the brain and is responsible for synchronizing internal rhythms. However, recent evidence underscores the importance of other hypothalamic nuclei in regulating several essential rhythmic biological functions. These extra-SCN hypothalamic nuclei also express circadian rhythms, suggesting distinct regions that oscillate either semi-autonomously or independent of SCN innervation. Concurrently, the extra-SCN hypothalamic nuclei are also sensitized to fluctuations in nutrient and hormonal signals. Thus, food intake acts as another powerful entrainer for the hypothalamic oscillators’ mediation of energy homeostasis. Ablation studies and genetic mouse models with perturbed extra-SCN hypothalamic nuclei function reveal their critical downstream involvement in an array of functions including metabolism, thermogenesis, food consumption, thirst, mood and sleep. Large epidemiological studies of individuals whose internal circadian cycle is chronically disrupted reveal that disruption of our internal clock is associated with an increased risk of obesity and several neurological diseases and disorders. In this review, we discuss the profound role of the extra-SCN hypothalamic nuclei in rhythmically regulating and coordinating body wide functions.

show abstract

Section: Melatoninmentioning

confidence: 99%

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Drunen

Eckel‐Mahan

2021

Clocks & Sleep

View full text Add to dashboard Cite

show abstract

“…Of note, the gut microbiota is also required for the hepatic clock daily oscillations that regulate metabolic gene expression for optimal liver function [102][103][104]. In fact, the liver and gut are in close anatomical and functional relation via the portal vein.…”

mentioning

confidence: 99%

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

et al. 2020

View full text Add to dashboard Cite

Non-alcoholic fatty liver disease (NAFLD) is often the hepatic expression of metabolic syndrome and its comorbidities that comprise, among others, obesity and insulin-resistance. NAFLD involves a large spectrum of clinical conditions. These range from steatosis, a benign liver disorder characterized by the accumulation of fat in hepatocytes, to non-alcoholic steatohepatitis (NASH), which is characterized by inflammation, hepatocyte damage, and liver fibrosis. NASH can further progress to cirrhosis and hepatocellular carcinoma. The etiology of NAFLD involves both genetic and environmental factors, including an unhealthy lifestyle. Of note, unhealthy eating is clearly associated with NAFLD development and progression to NASH. Both macronutrients (sugars, lipids, proteins) and micronutrients (vitamins, phytoingredients, antioxidants) affect NAFLD pathogenesis. Furthermore, some evidence indicates disruption of metabolic homeostasis by food contaminants, some of which are risk factor candidates in NAFLD. At the molecular level, several models have been proposed for the pathogenesis of NAFLD. Most importantly, oxidative stress and mitochondrial damage have been reported to be causative in NAFLD initiation and progression. The aim of this review is to provide an overview of the contribution of nutrients and food contaminants, especially pesticides, to oxidative stress and how they may influence NAFLD pathogenesis.

show abstract

“…Indeed, bioactive molecules produced or transformed by gut microorganisms interact with the host physiology and trigger responses locally and remotely (Michaudel and Sokol, 2020). It was demonstrated that gut microbiota had their own diurnal oscillations in composition and function, and the microbes and their metabolites might be associated with the detrimental consequences of circadian disturbance for host metabolism (Thaiss et al, 2014;Alvarez et al, 2020). Microbiota-generated metabolites bridge the hostmicrobiota interactions and may be essential for human physiology.…”

Section: Introductionmentioning

confidence: 99%

“…2) bile acids, synthesized in the liver from cholesterol and transformed by intestinal microbiota into the secondary bile acids (Sayin et al, 2013); and 3) tryptophan (Try) and its derivatives, including indole, kynurenine, and downstream products [e.g., 5-hydroxytryptamine (5-HT)] (Agus et al, 2018). Several studies have demonstrated interactions between microbial metabolites and circadian rhythms (Alvarez et al, 2020;Matenchuk et al, 2020). However, currently very few studies have examined the global changes in gut microbial metabolites upon circadian rhythm disturbance.…”

Section: Introductionmentioning

confidence: 99%

Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice

Wang

Qiu

et al. 2021

Front. Cell. Infect. Microbiol.

View full text Add to dashboard Cite

BackgroundEvidence suggests that circadian rhythm disorder is associated with a variety of gastrointestinal diseases, and the circadian rhythm plays a key role in maintaining the homeostasis of intestinal flora. The underlying mechanisms are still not completely identified. This study was aimed to explore whether jet lag-caused circadian disruption influences gut microbiome and its metabolites.MethodsMice were synchronized with 12-h light/dark cycles (control group) or subjected to daily 8-h advance of the light/dark cycle for every 3 days (jet-lagged group). Four months later, fecal samples and jejunal contents were collected and analyzed by 16S rRNA gene sequencing. In addition, fecal samples were subjected to metabolome analysis with ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS).ResultsThe results of 16s rRNA sequencing showed that chronic jet lag led to decreased microbial abundance, richness, and diversity in both feces and jejunal contents. ANOSIM analysis revealed significant difference between control and jet-lagged groups. As the colonic microbiome, the abundance of Bacteroidetes phylum was significantly decreased and that of Actinobacteria phylum was increased in jet-lagged mice. Jet lag increased the ratio of Firmicutes to Bacteroidetes, an indicator for the imbalance of gut microbiota. Metabolome analysis of fecal samples showed that the levels of tryptophan and its derivatives were decreased in jet-lagged mice. In addition, fecal levels of secondary bile acids changed under jet lag conditions. Correlation analysis identified associations between tryptophan (and its derivatives) levels and colonic microbiota.ConclusionsThis study presents a comprehensive landscape of gut microbiota and its metabolites in mice subjected to chronic jet lag. The results suggest that circadian disruption may lead to changes in fecal and jejunal microbiota and fecal metabolites. Moreover, our results demonstrate a novel interplay between the gut microbiome and metabolome.

show abstract

The Microbiome as a Circadian Coordinator of Metabolism

Cited by 30 publications

References 96 publications

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Circadian Rhythms of the Hypothalamus: From Function to Physiology

Oxidative Stress in NAFLD: Role of Nutrients and Food Contaminants

Chronic Jet Lag Exacerbates Jejunal and Colonic Microenvironment in Mice

Contact Info

Product

Resources

About