Obesity

Bacterial circadian clocks and obesity: Potential Role for the Gut Microbiota in Modulating Host Circadian Rhythms and Metabolic Health

Keyword: Search. Hormones such as growth hormone, testosterone, and estradiol secretion are all altered in germ-free mice, and the levels of ghrelin, which controls appetite and thus the timing of food, are reduced in the presence of microbes such as Bifidobacterium and Lactobacillus , and increased in the presence of Bacteroides and Prevotella in rodents.

Broad-spectrum antibiotics given to jet lagged mice with gut dysbiosis rescued them from these metabolic changes, indicating a potential role for gut bacteria in inducing the metabolic pathologies of jet lag. Additionally, in humans, time-of-day-dependent variations in gut commensals have been observed and, importantly, jet-lag induced time-related alterations in the microbial community Thaiss et al. Verdam F. Obesity is a major risk factor for several co-occurring diseases, including type II diabetes mellitus, non-alcoholic fatty liver disease, and ischemic cardiovascular disease, and the prevalence of these diseases has increased at an astounding rate in the past decades 1. Is bile acid a determinant of the gut microbiota on a high-fat diet? Sun Q.

  • Moreover, some evidence is indicating that diurnal microbial SCFA levels also influence on intestinal motility 33 ,

  • The findings, reported online yesterday in Cellcame as a surprise, Elinav says. Yamazaki, Y.

  • Homeostasis in intestinal epithelium is orchestrated by the circadian clock and microbiota cues transduced by TLRs.

Microbe-host interaction

Jet Lag Transmeridian or frequent multi-time-zone travel obewity jet lag, a syndrome manifested by delayed physiological adaptation to rapid changes in time zone. Holscher HD. Intestinal flora modulates blood pressure by regulating the synthesis of intestinal-derived corticosterone in high salt-induced hypertension. This factor is required for the differentiation of the conventional dendritic cell 1 cDC1 subset involved in cross-presentation 46 In humans, most bacterial fermentation occurs in the large intestine.

Carmen Leitch. Stratmann et al. In addition, CR affects responses of the circadian system to light, indicating that energy metabolism modulates gating of photic inputs in mammals [ ]. These patterns coincide with changes in factors that can affect cardiovascular function, such as stress hormone levels, heart rate, or activity of the autonomic nervous system. A study published by Cell Press October 16th in Cell now reveals that gut microbes in mice and humans have circadian rhythms that are controlled by the biological clock of the host in which they reside. Vykhovanets, and M.

  • Effects of antibiotics, minocycline and ampicillin, on human sleep.

  • Lu, T. Vollmers, A.

  • The increased levels of circulating bile acids in type 2 diabetic mice [ 78 ], indicates a much lower functional abundance of bsh in diabetes compared to control, which was corroborated with a metadata analysis [ 73 ]. Brouwer, A.

  • Maywood et al.

Eide, H. Mear, and R. People with diabetes also show differences in gut microbiota composition and altered oscillations of circadian clock genes compared to healthy individuals. During the light phase, microbes went about ongoing "housekeeping" processes, such as detoxifying, sensing the chemicals around them, and building the flagella, or tails, that help the microbes move.

Moreira, G. Thus, and obesity vitamin D3 levels can influence intestinal biogeography, and thereby microbial colonization. This is a consequence of the direct interaction between host cells and microbes or their signaling molecules, such as metabolites, which can reach and exert their effects in distal tissues. Mechanisms by which host immune system mediates the crosstalk between gut microbiota and host physiology. Additionally, relative abundances of different phyla varied between treatments, with Verrucomicrobia dramatically blooming at the expense of Firmicutes in the parenteral group.

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Sign up for Nature Briefing. Microbiome 514 Trans-kingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. Clocks and obesity built up H 2 S caused cicradian the bloom of sulfate reducers increase in dsrAB has been shown to strongly inhibit mitochondrial oxidation processes, and also phase-delay peripheral clocks. Impact of eating frequency on the microbiota Although there is considerable research on eating frequency and health, the impact of eating frequency on the GI microbiome has only recently been explored.

Nuclear receptor expression links the circadian clock to metabolism. Irrespective, this effect is of significant interest given that trends of circadian entrainment emerge with diet and and obesity meal timings rather than pharmacological intervention. Circadian disruption for a period of four weeks based on a regime of constant light exposure was also studied in ad libitum -fed mice. Marianelli C. In line with this, a study in rats showed that depletion of gut microbiota using antibiotics reduced slow wave sleep [ 37 ]. Zarrinpar, A.

Dube, and P. Boulamery-Velly, N. Keen, and J. These results suggest that loss of circadian rhythmicity of glucose metabolism may contribute to the development of metabolic disorders, such as type 2 diabetes [ 74 — 78 ]. Teague, W.

Alzheimer's Dis. Methods Enzymol. Germ-free mice displayed reduced core clock gene oscillation in the mediobasal hypothalamus Leone et al. Effect of sleep deprivation on the human metabolome.

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One such important pioneering work revealed that gut microbes synchronize vacterial intestinal epithelial clock and glucocorticoid production through interaction with Toll-like receptors TLRswhich are linked to the circadian oscillators Mukherji et al. Irrespective, this effect is of significant interest given that trends of circadian entrainment emerge with diet and adjusting meal timings rather than pharmacological intervention. External link.

The gut—brain axis is an integrative system of bidirectional communication between the qnd and the gastrointestinal GI tract. We acknowledge that in isolation, none of the above factors solve the metabolic issues arising from chronic circadian disruption, but given that modern lifestyles are here to stay, dietary manipulations are probably something that consumers are willing to try. Sleep Sci. We propose a microbially-mediated mechanism of circadian disruption that involves alterations in the distinct time-of-day microbial signatures. Tlr2 is critical for diet-induced metabolic syndrome in a murine model.

Eckel-Mahan, K. To obtain the best experience, we recommend you use a more bacterial circadian clocks and obesity to date browser or turn off compatibility mode in Internet Explorer. In summary, host microbial rhythms may be considered a composite of peaks by the host-glycan foragers primarily Bacteroidetes, but also Verrucomicrobia, and the opportunistic Enterobacteriaceae anti-phase to thediet-driven Firmicutes peaks. This has been demonstrated in epidemiological studies indicating that long-term alteration of sleep patterns increases the risk of obesity and metabolic disorders

Circadian Rhythms in Non-Photosynthesizing Bacteria

These endogenous time keeping mechanisms are called circadian clocks. Ueda, W. The last several years have seen an explosion of interest in the constellation of bacteria that call the gut home, and these microbes appear to play a role in everything from immunity to metabolism to mood.

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  • Box 12, Rehovot, Israel.

  • Finally, the possible implication of daily rhythm on the gut-microbiome-brain axis will be analyzed, focusing on the reciprocal effects of clock disruption and microbiota alterations on brain function and behavior.

  • Yi, J. Knight says some of the strongest evidence for a bacterial role in circadian-linked diseases lies in the final phase of the study, when the research team analyzed fecal samples from two people on a normal schedule and two more who had recently flown from the United States to Israel.

Organisms ranging from bacteria to humans have circadian clocks to help them synchronize their biological activities to the time of day. Lipan, I. Hayashi, Y. Grimaldi et al.

Chaump, and Bacterial circadian clocks and obesity. Cappendijk, and F. Several studies have examined how changes in relationship between circadian rhythms, the vircadian, and the brain affect disease risk and severity, but the molecular mechanisms underlying this interaction remain unclear. Fatty acids or their metabolites can modulate neuronal activity by brain nutrient-sensing neurons involved in the regulation of energy and glucose homeostasis. Kalsbeek, M. Upcoming Virtual Events. One major difference between normal mice and clock-disabled ones was the time at which the animals ate, the researchers observed.

The biological clocks of the circadian timing system coordinate cellular and physiological processes and synchronizes these with daily cycles, feeding patterns also regulates circadian clocks. Having a regular bedtime may have numerous health benefits for adults as well. Yamazaki, P. B48—B53, Lau, S. Figure 1. Weaver, S.

Related articles

Interestingly enough, studies have shown that ingesting probiotics may help obesity melatonin secretion and sleeping quality, opening a door for the future use of probiotics for sleep regulation and health. Therefore, network regulation of the microbiota and the circadian clock in the intestinal tract is a critical process to control obesity and insulin resistance Therefore, there is an urgent need to identify host and environmental factors that regulate human metabolism and energy homeostasis. Int Rev Neurobiol.

Genetic ablation of core-clock components and induction of jet-lag lead to dysbiosis, which subsequently impairs host metabolic homeostasis, such as glucose metabolism Thaiss et al. Human gut microbiome: hopes, threats and promises. This molecular clock mechanism plays an important role in regulating the rhythmic expression of clock-controlled genes, which in turn regulate the synthesis, storage, and expenditure of energy [ 1 ]. Western diets high in fat and refined sugars, and low in fibre influence key microbial oscillators to disrupt host circadian rhythms and metabolism to promote obesity. Furthermore, individuals who work night shifts experience an almost complete reversal of food intake, with intake occurring primarily during the night and rest and fasting occurring during daylight hours. MYC disrupts the circadian clock and metabolism in cancer cells. Moreover, the functional feature generated by the microbiota oscillations feeds into the circadian clock network not only in the intestine but also in the system as a whole

Important for brain circasian by regulating brain clock genes bacterial circadian clocks and obesity 97 ]; lowered serum B9 associated with sleep disturbance [ 90 ]. Several bacteria strains has the capability to synthetize or to contribute to the metabolism of neuromodulators Strandwitz, Circadian disorganization alters intestinal microbiota. Carcinogenesis 26— Touitou, Y. In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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Circadian oscillations of protein-coding and regulatory RNAs in a highly dynamic mammalian liver epigenome. The microbiome-gut-brain axis during early life regulates the hippocampal serotonergic system in a sex-dependent manner. Hardeland R. Chen, S.

Yamazaki, Y. An EKG measures the electrical activity of your heart and assesses if it has been damaged, such as from a heart attack. Feillet, J. Thus, shift work is associated with increased risk for obesity, diabetes and cardio-vascular diseases as a result of unusual eating time and disruption of circadian rhythm. Thus, how RF entrains circadian rhythms remains an extremely important topic for research.

Chen, A. Vaginome: understanding the vaginal microbiome. Roar Like a Lion T-Shirt. Consequently, disruption of clock genes results in dyslipidemia, insulin resistance and obesity.

Email address Sign up. Bass, J. Wilkinson, M. In mammals, including humans, this endogenous clock is organized in a hierarchical system characterized by several tissue clocks whose diurnal oscillation is orchestrated by a master clock located in the suprachiasmatic nucleus Partch et al.

Circadian Rhythms and the Gut Microbiota

Regulation of host weight gain and lipid metabolism by bacterial bile acid modification in the gut. Transkingdom control of microbiota diurnal oscillations promotes metabolic homeostasis. EBioMedicine 32—

Defective uptake and utilization of long chain fatty acids in muscle and adipose tissues of CD36 knockout mice. Feng, R. Vitamins Some B vitamins have been directly or indirectly linked with circadian rhythms bacterial circadian clocks and obesity sleep patterns [ 8990 ]. Disruption of the circadian system can alter microbiome communities and can perturb host metabolism, energy homeostasis and inflammatory pathways, which leads to the metabolic syndrome. Further reading Association between serum low-density lipoprotein cholesterol and metabolic syndrome in a working population Saibin Wang Lipids in Health and Disease A lasting symbiosis: how the Hawaiian bobtail squid finds and keeps its bioluminescent bacterial partner Spencer V.

For most circadin, asthma symptoms are worse at night than during the day. But DNA replication takes three to four hours to replicate the entire genome, so there's a fundamental need to predict the future. Almost all living organisms have evolved autoregulatory transcriptional-translational feedback loops that produce oscillations with a period of approximately h. Simon, J. Van Der Vliet, J.

Hitosugi et al. Hawley, and J. Moreover, timed high-fat diet led to reduced body weight and improved metabolism compared to animals bacteeial consumed the same caloric intake spread out throughout the day [ ] see below. The host's circadian clock and normal feeding habits were required for the generation of these rhythmic fluctuations in the gut microbes. McCann, and J. Some pikas survive the winter by eating yak poop By Rachel Fritts Jul. When they analyzed microbes found in fecal samples collected from mice and humans at different times of day, they discovered rhythmic fluctuations in the abundance of microbes and their biological activities.

1. Introduction

Oral administration of SCFAs to antibiotic-treated and obesity changed the rhythms of two genes that play major role in the circadian clock. The bacteial SCN clock resets signals in peripheral tissues, such as muscle, fat tissue, digestive tract, and liver. During the dark phase when mice, being nocturnal, are most activethe bacteria were busy digesting nutrients, repairing their DNA, and growing, as evidenced by the various bacterial gene activity documented from fecal samples taken at different time points.

Potential mechanism of gut microbiota interactions in the circadian—metabolic axis. Hydrogen sulfide. Circadian clock gene expression is impaired in gestational diabetes mellitus. A preferential overgrowth of streptococci and other oropharyngeal, and colonic microflora has been observed in the gastrointestinal disorder, small intestinal bacterial overgrowth [ 41 ]. Print Email Share.

Wallen, and F. Received 16 Oct Data has shown that heart attacks are more likely to occur in the morning, while asthma symptoms and fever are more likely to be worse in the afternoon and evening. Gorbacheva, O. Eide, H.

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Firmicutes Lachnospiraceae, Clostridiaceae, Erysepelotrichaceae, Ruminococcaceae, LactobacillusBacteroidetes Bacteroidesand Bifidobacterium [ 7273 ]. Loonen, L. The immediate effects on energy resources for colonic epithelial cells, and peripheral effects on substrate oxidation via systemic circulation potentially impact energy homeostasis. The gut ecosystem is the most well-studied component of the body's microbial ecosystem.

Conrad et al. Researchers are learning more about how your circadian rhythms affect your overall health. Ottinger, M. Crapo, M. These changes in catabolic and anabolic pathways altered liver metabolome and improved nutrient utilization and energy expenditure [ ]. Staying healthy with the body clock.

Close banner Close. Kennedy, Bacterial circadian clocks and obesity. Therefore, network regulation of the aand and the circadian clock in the intestinal tract is a critical process to control obesity and insulin resistance Barak, Y. Disruption of the circadian system can alter microbiome communities and can perturb host metabolism, energy homeostasis and inflammatory pathways, which leads to the metabolic syndrome. Consequences of exposure to light at night on the pancreatic islet circadian clock and function in rats.

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Hemmers S, Rudensky AY. This colonic microbial biotransformation includes deconjugation by bile salt hydrolases bshfollowed by dehydroxylase and dehydrogenase activity, attributed to bacteria mostly from Firmicutes Lachnospiraceae, Clostridiaceae, Erysepelotrichaceae, Ruminococcaceae, LactobacillusBacteroidetes Bacteroidesand Bifidobacterium [ 7273 ]. Hirano A. Some observational evidence links differences in eating frequency with varying health effects in humans Table 3.

Cardiovascular disease. Pitts, E. Takahashi, H. Ueda, W. Cardinali, and A.

  • This is thought to be the result of dramatic changes in the human lifestyle, ranging from a drastic change in dietary patterns, improved hygiene, and altered sleep cycles. Reprints and Permissions.

  • Ingram, M. But the influence of the microbiota and circadian rhythms goes beyond the endocrine system.

  • Do antibiotics affect sleep or circadian-controlled metabolic states?

Sleep Med. Circadian disruption for a period of four weeks based on a regime of constant light exposure was also studied in ad libitum -fed mice. Rapid fucosylation of intestinal epithelium sustains host-commensal symbiosis in sickness. This dsrAB is present predominantly in Deltaproteobacteria such as Desulfovibrio, Desulfotobacter, Desulfobulbus, and the taurine utilising Bilophila wadsworthiacausing a net increase in H 2 S in the distal colon [ 13 ]. Acta Physiol. Metabolic syndrome and cancer.

Note: Content may be edited for style and length. One of the key tissues that regulate metabolism is the adipose tissue. Zee, and F. AUG 17,

MINI REVIEW article

Per2 phase advances were seen even in submandibular salivary glands, albeit significantly only at day 2 [ 62 ]. Cancer Commun. For example, the circadian clock modulates inflammatory response during Salmonella typhimurium infection, and a functional clock is required for maximal induction of pro-inflammatory genes Bellet et al.

  • Recently, there is some evidence indicating a role for temporal and spatial dynamics in the community of microorganisms that inhabit the gastrointestinal tract.

  • Bernardi, L. Keen, and J.

  • Reduced anxiety-like behavior and central neurochemical change in germ-free mice.

  • Keywords: circadian clocks; gut microbiota; hormone; leptin; lipid metabolism; melatonin; obesity. Meister, and S.

Cell Host Microbe 28— Dietary intake that is misaligned with the natural rhythms of the circadian clock has been shown to negatively impact human health. Gut microbiota in human adults with type 2 diabetes differs from non-diabetic adults. Daulatzai M. Of note, gut microbes influence host metabolism through widespread reprogramming of circadian transcriptional activity.

  • Wang et al. Wong R.

  • Wan, and Z.

  • She is really concern about health of the population and believe that with a better diet and lifestyle we can all make ourselves healthier. These observations are particularly relevant because of the roles gut microbiota play in maintaining whole body health.

  • Potential role for the gut microbiota in modulating host circadian rhythms and metabolic health. Cite this article Bishehsari, F.

  • Ottinger, M.

Winters, and P. The IF-induced beneficial effects are thought to occur independently of the overall caloric intake, but the underlying mechanisms are still unknown. Hardie, S. Kalra, M. CR refers to a dietary regimen low in calories without malnutrition.

Intestinal barrier circaddian gut microbiota: shaping our immune responses throughout life. Backhed, F. Clinical translation of microbe-based therapies: current clinical landscape and preclinical outlook. Sulli, G. Metabolites are another interesting class of molecules, which could bring microbial-derived information from the periphery to the brain. Alterations in the colonic flora and intestinal permeability and evidence of immune activation in chronic constipation.

Publication types

Several functions circadjan IECs, including nutrient absorption, cell proliferation, motility, and metabolic activities are regulated in bacterial circadian clocks and obesity circadian rhythm. Such analysis of microbial abundance is generally expressed as relative abundance of different bacteria in a sample. Acute sleep deprivation caused an increase in urinary metabolites, including those generated by gut bacteria. A smartphone app reveals erratic diurnal eating patterns in humans that can be modulated for health benefits. Arrhythmic gut microbiome signatures predict risk of type 2 diabetes.

Consequently, bidirectional obesity between host and microbial circadian rhythmicity orchestrate local and systemic physiology. Obesity 21E—E Meal timing regulates the human circadian system. She is really circaxian about health of the population and believe that with a better diet and lifestyle we can all make ourselves healthier. Circadian Clock and Metabolic Disorders Circadian rhythms are a very exquisite mechanism by which organisms can adapt their behaviors to the h light-dark LD cycle change in the external environment evoked by the rotation of the earth around the sun Unconjugated bile acids influence expression of circadian genes: a potential mechanism for microbe-host crosstalk. External link.

Damiola, N. Living Well. View at: Google Scholar. Landry, M.

Yildiz, M. Yamazaki, M. One major difference between normal mice and clock-disabled ones was the time at which the animals ate, the researchers observed. Similarly, glucose uptake and adenosine triphosphate ATP concentrations exhibit circadian fluctuations in brain and peripheral tissues [ 525556 ]. Takumi, and S. Ciani, and A. View at: Google Scholar H.

INTRODUCTION

Herzog, J. Desvergne, and W. These findings place leptin as a major bridge linking energy homeostasis and circadian control.

Solberg, and F. The TimeSignature test offers insights into your body's time compared to external time. Metabolic effects Several studies suggest that metabolic disorders can arise from the interaction between diet and other environmental factors, including circadian rhythm disruption and changes in the composition of the gut microbiota. In another studynasal secretions during a cold were highest in the early morning, decreased during the day, and increased a little in the evening. Weindruch and R. Organisms on our planet evolved to predict these cycles by developing an endogenous circadian circa : about and dies : day clock, which is synchronized to external time cues. Wan, M.

It's not just for kids. But as larger studies are done, the effects of mealtime on health will become more clear. Gooley, A. Retrieved July 29, from www.

Circadian disorganization alters intestinal microbiota. Cell Host Microbe 17— Wang, Z. Clavel T. Circadian gene Bmal1 regulates diurnal oscillations of Ly6C hi inflammatory monocytes. Masters, S.

Key points

Quintero, S. Aspirin may help reduce risk for heart attack, but it may also have some risks. Kaluzova, B.

  • Riemann, D.

  • Recent work has shown that even bacteria respond to a circadian rhythm.

  • Diabetes 50— Microbial Regulation of Circadian Physiology Recent evidence demonstrated that commensal bacteria play an essential role in the circadian regulation of host physiology.

  • Cell Metab.

  • One may thus conclude that periods of fasting are critical for ensuring the representation of bacteria that are otherwise outcompeted by the increase of Firmicutes after meal times, to break down dietary carbohydrates that reach the colon. According to the authors, constant darkness disrupted microbial rhythmicity in both small and large intestinal segments, but sampling was not performed according to circadian time and the figures indicate a free-running rhythm rather than disruption.

Circadian regulation of depression: a role for serotonin. Diet and feeding pattern affect the diurnal dynamics of the gut microbiome. Rhythmic histone acetylation underlies transcription in the mammalian circadian clock. Access through your institution. Acute sleep deprivation caused an increase in urinary metabolites, including those generated by gut bacteria.

The metabolic syndrome has direct effects on health and increases the risk of developing cancer. Clin Gastroenterol Hepatol. Dietary intake that is misaligned with the natural rhythms of the circadian clock has been shown to negatively impact human health. While there are multiple factors such as sleep, hormone rhythms, and dietary intake that are changed during jet lag, recent studies have demonstrated relationships between jet lag, gut microbial dysbiosis, and dysfunctional metabolic homeostasis. Elevated expression of the toll like receptors 2 and 4 in obese individuals: its significance for obesity-induced inflammation.

Watanabe, K. Lee, C. Food anticipatory activity is mediated by a self-sustained circadian timing and its principal component is food entrained oscillator. Saeb-Parsy, S.

David-Gray, and R. During the light phase, microbes went about ongoing "housekeeping" processes, such as detoxifying, sensing the chemicals around them, and building the flagella, or tails, that help the microbes move. Comperatore and F. Mendoza, C. Wang, S.

  • Voigt, R. A healthy diet that is high in fiber and a regular eating schedule during the day are tools we can easily access for improved gut microbiota rhythmicitymeanwhile behaviors that include eating late at night, alcohol consumption and sleep disruption need to be avoided.

  • Retrieved July 29, from www.

  • Therefore, while the LD cycle resets the master clock in the SCN, the timing of food intake can be a potent synchronizer of peripheral clocks. The human gut can comprise up to species, the number and proportions of which vary with a number of factors including mode of birth, age, gender, body mass, diet, health status, intake of medications especially antibiotics, activity, and travel [ 101116 ].

  • This might happen for several microbiota-derived metabolites and signaling molecules, with relevant consequences for CNS physiopathology and behavior. Microbial dysbiosis due to intestinal disease.

  • These widespread behavioral patterns have been linked to a wide range of diseases, including obesity, diabetes, cancer, and cardiovascular disease.

  • But, mice with a T-cell-specific deletion of Bmal1 had normal differentiation of T H 17 cells 55suggesting no intrinsic role of circadian clocks in the T cell response of the intestinal tract. Microbiome rhythmicity is mainly attributed to host feeding behavior and a functional host circadian clock.

Qian, J. Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss. Microbiome dynamics in obesity. The GI microbiome oebsity essentially a microbial organ that provides metabolic, immunologic, and protective functions for the host. In both its phosphorylated and dephosphorylated states, KaiC indirectly modulates gene expression via interactions with other protein regulators. Importantly, the microbial products or components can also orchestrate the circadian network.

Circadian rhythm, gut microbiota, and metabolism. This sleep restriction did not alter any of the major phyla compared to baselinealthough aand did increase a pro-inflammatory candidate phylum TMa that was not restored after four days of sleep recovery. While there are multiple factors such as sleep, hormone rhythms, and dietary intake that are changed during jet lag, recent studies have demonstrated relationships between jet lag, gut microbial dysbiosis, and dysfunctional metabolic homeostasis. Zhang, R. Silver, A. Bacterial bioluminescence regulates expression of a host cryptochrome gene in the squid-Vibrio symbiosis. But what about bacteria?

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