Genetic and environmental circadian disruption induce weight gain through changes in the gut microbiome

Altaha, Baraa; Heddes, Marjolein; Pilorz, Violetta; Niu, Yunhui; Gorbunova, Elizaveta; Gigl, Michael; Kleigrewe, Karin; Oster, Henrik; Haller, Dirk; Kiessling, Silke

doi:10.1016/j.molmet.2022.101628

Cited by 17 publications

(15 citation statements)

References 65 publications

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“…Indeed, transfer of intestinal clock-controlled (arrhythmic) microbiota and metabolites resulted in an obesity phenotype in recipients, reflected by increased bodyweight and substantially increased fat mass. Consistently, previous studies, including our own, detected metabolic alterations in recipient mice following transfer of microbiota collected from humans and mice during circadian disruption (Altaha, 2022;Thaiss et al, 2014). In accordance to findings obtained from SPF Bmal1 IEC-/mice, families like Muribaculacea and Lachnospiraceae, lost rhythmicity in Bmal1 IEC-/recipient.…”

Section: Discussionsupporting

confidence: 91%

“…These results suggest the importance of the intestinal clock in microbiome mediated metabolic homeostasis. This hypothesis is strengthened by our transfer experiments suggesting that loss of microbial rhythmicity promotes metabolic abnormalities of the host (Altaha, 2022;Heddes et al, 2022). In addition, diet is a prominent modulator of gut microbial composition and was recently linked to microbial rhythmicity.…”

Section: Introductionmentioning

confidence: 58%

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The Intestinal Clock Regulates Host Metabolism through the Fiber-Dependent Microbiome and Macronutrient Transcriptome

Heddes

Niu

Altaha

et al. 2023

Preprint

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Circadian disruption, e.g. through shift work, causes microbial dysbiosis and increases the risk of metabolic diseases. Microbial rhythmicity in mice depends on a functional intestinal clock and frequent jetlag and high-caloric energy intake induces loss of these oscillations. Similarly, arrhythmic microbiota was found in obese and T2D populations. However, the interplay between the intestinal circadian clock, the microbiome, diet and host metabolism is poorly understood. In intestinal-specific Bmal1 knockout mice (Bmal1IEC-/-) we demonstrate the relevance of the intestinal clock in microbiome oscillations and host and microbial nutrient metabolism. Microbiota transfer from Bmal1IEC-/- mice into germ-free recipients led to obesity, reflected by increased bodyweight and fat mass. Western diet-fed Bmal1IEC-/- mice increased bodyweight likely through mechanisms involving the intestinal clock-control of lipid and hexose transporters. Additionally, we identified dietary fiber as novel link between circadian microbial rhythmicity, intestinal clock functioning and host physiology. Thus, fiber-rich diet intervention might become a potential non-invasive prevention strategy to target microbial oscillations in people at risk to develop metabolic diseases.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 58%

The Intestinal Clock Regulates Host Metabolism through the Fiber-Dependent Microbiome and Macronutrient Transcriptome

Heddes

Niu

Altaha

et al. 2023

Preprint

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“…Microbiota transfer experiments further demonstrated the physiological relevance of microbial oscillations for the host's metabolic and gastrointestinal health. 26,45,48 Since environmental factors, such as the light-dark-cycle, or time of food intake, are potent signals impacting microbial rhythms, 26,45,48,49 abnormal light or food exposure can alter microbial oscillations and thus might lead to the development of pathologies and disease. To gain further insights into the possible functionality of microbiota oscillations in infants, rhythmic zOTU-associated pathways were examined.…”

Section: Discussionmentioning

confidence: 99%

“…Growing evidence provides a link between loss of rhythmicity and disease pathology 27 . Animal studies determined the origin of these bacterial oscillations to reside in the circadian system 28–30 , particularly the intestinal circadian clock 31 . The mammalian circadian system develops in utero, which continues during aging and plays an important role during development 32 .…”

Section: Mainmentioning

confidence: 99%

Diurnal rhythmicity of fecal microbiota and metabolite profiles in the first year of life: a randomized controlled interventional trial with infant formula

Heppner,

Reitmeier,

Heddes

et al. 2023

Preprint

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Microbiota assembly in the infant gut is influenced by time and duration of dietary exposure to breast-milk, infant formula and solid foods. In this randomized controlled intervention study, longitudinal sampling of infant stools (n=998) showed similar development of fecal bacterial communities between formula- and breast-fed infants during the first year of life (N=210). Infant formula supplemented with galacto-oligosaccharides (GOS) was most efficient to sustain high levels of bifidobacteria compared to formula containingB. longumandB. breveor placebo. Metabolite (untargeted) and bacterial profiling (16S rRNA/shallow metagenomics sequencing) revealed 24-hour oscillations and integrated data analysis identified circadian networks. Rhythmicity in bacterial diversity, specific taxa and functional pathways increased with age and was most pronounced following breast-feeding and GOS-supplementation. Circadian rhythms in dominant taxa were discoveredex-vivoin a chemostat model. Hence microbiota rhythmicity develops early in life, likely due to bacterial intrinsic clock mechanism and is affected by diet.

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“…60,61 Additionally, previous studies have indicated that factors other than the central clock, such as diets and the GM, may also synergistically influence peripheral circadian rhythms and impact the functions of the gut and liver. [62][63][64] For instance, the disruption of intestinal clocks and subsequent loss of rhythmicity in bacterial taxa responsible for short-chain fatty acids (SCFAs) production can lead to metabolic abnormalities, 65 and the GM usually act as a transducer of dietary cues to regulate the host's CC and metabolism. 66 Hence, we proposed that the minimal impact of different LD cycles on hepatic CC could be attributed to the regulation of the GM or gut cells.…”

Section: The Role Of Gm In Regulating Hepatic Circadian Rhythms Under...mentioning

confidence: 99%

Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light–dark cycles: A multiomics study

Zhen,

Wang,

et al. 2023

Journal of Pineal Research

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The accelerated pace of life at present time has resulted in tremendous alterations in living patterns. Changes in diet and eating patterns, in particular, coupled with irregular light–dark (LD) cycles will further induce circadian misalignment and lead to disease. Emerging data has highlighted the regulatory effects of diet and eating patterns on the host‐microbe interactions with the circadian clock (CC), immunity, and metabolism. Herein, we studied how LD cycles regulate the homeostatic crosstalk among the gut microbiome (GM), hypothalamic and hepatic CC oscillations, and immunity and metabolism using multiomics approaches. Our data demonstrated that central CC oscillations lost rhythmicity under irregular LD cycles, but LD cycles had minimal effects on diurnal expression of peripheral CC genes in the liver including Bmal1. We further demonstrated that the GM could regulate hepatic circadian rhythms under irregular LD cycles, the candidate bacteria including Limosilactobacillus, Actinomyces, Veillonella, Prevotella, Campylobacter, Faecalibacterium, Kingella, and Clostridia vadinBB60 et al. A comparative transcriptomic study of innate immune genes indicated that different LD cycles had varying effects on immune functions, while irregular LD cycles had greater impacts on hepatic innate immune functions than those in the hypothalamus. Extreme LD cycle alterations (LD0/24 and LD24/0) had worse impacts than slight alterations (LD8/16 and LD16/8), and led to gut dysbiosis in mice receiving antibiotics. Metabolome data also demonstrated that hepatic tryptophan metabolism mediated the homeostatic crosstalk among GM‐liver–brain axis in response to different LD cycles. These research findings highlighted that GM could regulate immune and metabolic disorders induced by circadian dysregulation. Further, the data provided potential targets for developing probiotics for individuals with circadian disruption such as shift workers.

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Genetic and environmental circadian disruption induce weight gain through changes in the gut microbiome

Cited by 17 publications

References 65 publications

The Intestinal Clock Regulates Host Metabolism through the Fiber-Dependent Microbiome and Macronutrient Transcriptome

The Intestinal Clock Regulates Host Metabolism through the Fiber-Dependent Microbiome and Macronutrient Transcriptome

Diurnal rhythmicity of fecal microbiota and metabolite profiles in the first year of life: a randomized controlled interventional trial with infant formula

Homeostatic crosstalk among gut microbiome, hypothalamic and hepatic circadian clock oscillations, immunity and metabolism in response to different light–dark cycles: A multiomics study

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