The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Heddes, Marjolein; Altaha, Baraa; Niu, Yunhui; Reitmeier, Sandra; Kleigrewe, Karin; Haller, Dirk; Kiessling, Silke

doi:10.1101/2021.10.18.464061

Cited by 2 publications

(10 citation statements)

References 103 publications

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“…Transfer experiments using mouse models with circadian dysfunction provide direct evidence for the physiological relevance of microbiota rhythms for metabolic health. For example, transfer of arrhythmic microbiota from gut-clock deficient mice disrupts GI homeostasis in recipient animals [17], and microbiota from mice exposed to environmentally induces circadian disruption promoting body weight gain in wild type mice. Similar results were obtained following microbiota transfer from jet lagged mice [15].…”

Section: Discussionmentioning

confidence: 99%

“…3.2 Disruption of microbiota rhythmicity in SCN-specific Bmal1-deficient mice GI clocks are dominant regulators of circadian microbiome fluctuations and thereby balance GI homeostasis, as previously shown by us [17]. This prompted us to determine whether circadian desynchronization in GI tissues in Bmal1 SCNfl/mice affects circadian microbiota composition and function.…”

Section: Central Clock Dysfunction Induces Circadian Desynchronizatio...mentioning

confidence: 91%

“…We aligned the sequence by the maximum likelihood approach wuth MUSCLE from the software MegaX to generate phylogenetic trees and use the online tool Evolview for tree visualization (http://www.evolgenius.info/evolview) [24]. For quantitative analysis, we add spike of 12 artificial DNA that mimics 16s rRNA genes in order to determine 16s rRNA genes copy numbers per gram of fecal sample as previously described [17]…”

Section: Methodsmentioning

confidence: 99%

“…Interestingly, our results in prediabetic patients indicate that arrhythmicity of specific taxa precedes the onset of diabetes and a signature of arrhythmic bacteria predicts T2D risk in populations. Of importance, our recent work on mice identified clocks in cells of the GI tract to be the major regulators of microbial rhythmicity and, therefore, GI homeostasis [17]. Consequently, we hypothesize that intestinal clock-controlled oscillation of the microbiome provides a functional link to metabolic requirements of the host to maintain metabolic health.…”

Section: Introductionmentioning

confidence: 91%

mentioning

confidence: 99%

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Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

Altaha

Heddes

Pilorz

et al. 2022

Preprint

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Objective: Internal clocks time behavior and physiology, including the gut microbiome in a circadian (~24 h) manner. Mismatch between internal and external time, e.g. during shift work, disrupts circadian system coordination promoting the development of obesity and type 2 diabetes (T2D). Conversely, body weight changes induce microbiota dysbiosis. The relationship between circadian disruption and microbiota dysbiosis in metabolic diseases, however, remains largely unknown. Methods: Core and accessory clock gene expression in different gastrointestinal (GI) tissues were determined by qPCR in two different models of circadian disruption - mice with Bmal1 deficiency in the circadian pacemaker, the suprachiasmatic nucleus (Bmal1SCNfl/-), and wild-type mice exposed to simulated shift work (SSW). Body composition and energy balance were evaluated by nuclear magnetic resonance (NMR), bomb calorimetry, food intake and running-wheel activity. Intestinal permeability was measured in an Ussing chamber. Microbiota composition and functionality were evaluated by 16S rRNA gene amplicon sequencing, PICRUST2.0 analysis and targeted metabolomics. Finally, microbiota transfer was conducted to evaluate the functional impact of SSW-associated microbiota on the hosts physiology. Results: Both chronodisruption models show desynchronization within and between peripheral clocks in GI tissues and reduced microbial rhythmicity, in particular in taxa involved in short-chain fatty acid (SCFA) fermentation and lipid metabolism. In Bmal1SCNfl/- mice, loss of rhythmicity in microbial functioning associates with previously shown increased body weight, dysfunctional glucose homeostasis and adiposity. Similarly, we observe an increase in body weight in SSW mice. Germ-free colonization experiments with SSW-associated microbiota mechanistically link body weight gain to microbial changes. Moreover, alterations in expression of peripheral clock genes as well as clock-controlled genes (CCGs) relevant for metabolic functioning of the host were observed in recipients, indicating a bidirectional relationship between microbiota rhythmicity and peripheral clock regulation. Conclusions: Collectively, our data suggest that loss of rhythmicity in bacteria taxa and their products, which likely originates in desynchronization of intestinal clocks, promotes metabolic abnormalities during shift work.

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Section: Discussionmentioning

confidence: 99%

Section: Central Clock Dysfunction Induces Circadian Desynchronizatio...mentioning

confidence: 91%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 91%

mentioning

confidence: 99%

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Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

Altaha

Heddes

Pilorz

et al. 2022

Preprint

Self Cite

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The effects of ambient temperature and feeding regimens on cecum bacteria composition and circadian rhythm in growing rabbits

Shuai He,

Zhang,

Jin

et al. 2024

Front. Microbiol.

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Seasonal environmental shifts and improper eating habits are the important causes of diarrhea in children and growing animals. Whether adjusting feeding time at varying temperatures can modify cecal bacterial structure and improve diarrhea remains unknown. Three batches growing rabbits with two groups per batch were raised under different feeding regimens (fed at daytime vs. nighttime) in spring, summer and winter separately, and contents were collected at six time points in 1 day and used 16S rRNA sequencing to investigate the effects of feeding regimens and season on the composition and circadian rhythms of cecum bacteria. Randomized forest regression screened 12 genera that were significantly associated with seasonal ambient temperature changes. Nighttime feeding reduced the abundance of the conditionally pathogenic bacteria Desulfovibrio and Alistipes in summer and Campylobacter in winter. And also increases the circadian rhythmic Amplicon Sequence Variants in the cecum, enhancing the rhythm of bacterial metabolic activity. This rhythmic metabolic profile of cecum bacteria may be conducive to the digestion and absorption of nutrients in the host cecum. In addition, this study has identified 9 genera that were affected by the combination of seasons and feeding time. In general, we found that seasons and feeding time and their combinations affect cecum composition and circadian rhythms, and that daytime feeding during summer and winter disrupts the balance of cecum bacteria of growing rabbits, which may adversely affect cecum health and induce diarrhea risk.

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The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Cited by 2 publications

References 103 publications

Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

Genetic and environmental circadian disruption induce metabolic impairment through changes in the gut microbiome

The effects of ambient temperature and feeding regimens on cecum bacteria composition and circadian rhythm in growing rabbits

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