Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

Abstract

The intestinal microbiota undergoes diurnal compositional and functional oscillations that affect metabolic homeostasis, but the mechanisms by which the rhythmic microbiota influences host circadian activity remain elusive. Using integrated multi-omics and imaging approaches, we demonstrate that the gut microbiota features oscillating biogeographical localization and metabolome patterns that determine the rhythmic exposure of the intestinal epithelium to different bacterial species and their metabolites over the course of a day. This diurnal microbial behavior drives, in turn, the global programming of the host circadian transcriptional, epigenetic, and metabolite oscillations. Surprisingly, disruption of homeostatic microbiome rhythmicity not only abrogates normal chromatin and transcriptional oscillations of the host, but also incites genome-wide de novo oscillations in both intestine and liver, thereby impacting diurnal fluctuations of host physiology and disease susceptibility. As such, the rhythmic biogeography and metabolome of the intestinal microbiota regulates the temporal organization and functional outcome of host transcriptional and epigenetic programs.

Metronidazole Causes Skeletal Muscle Atrophy and Modulates Muscle Chronometabolism

“…The gut microbiota and its daily rhythmicity of produced metabolites is reported to modulate host circadian chromatin dynamics and transcriptome in intestine and liver [2]. It was proposed that microbiota-generated signals are integrated by peripheral tissues to temporally organize genome-wide transcription [2].…”

“…The gut microbiota and its daily rhythmicity of produced metabolites is reported to modulate host circadian chromatin dynamics and transcriptome in intestine and liver [2]. It was proposed that microbiota-generated signals are integrated by peripheral tissues to temporally organize genome-wide transcription [2]. The mammalian circadian clock is a transcriptional and translational negative feedback loop controlled by the core clock gene products Clock, Bmal1, Per1-3, and Cry1 and Cry2, eventually regulating many biological processes [38].…”

“…The gut microbiota primarily provides protection against pathogenic microorganisms and inflammation and helps with digestion and energy metabolism by modulating various host signaling pathways [1]. The daily rhythmicity of the gut microbiota and its metabolites modulates the host circadian rhythm [2]. Furthermore, gut dysbiosis and circadian rhythm disruption are associated with metabolic syndrome and diseases such as obesity, type 2 diabetes, and inflammatory bowel disease [3].…”

Complex interaction between circadian rhythm and diet on bile acid homeostasis in male rats

“…Gut microbiota deconjugate bile acids and convert primary bile acids into secondary forms. Microbiota have a strong day/night rhythm that affects circadian oscillations of plasma metabolites and the liver transcriptome and detoxification pattern (Thaiss et al 2016). As such, microbiota might also indirectly affect bile acid composition besides intraluminal deconjugation and de hydroxylation.…”

Natur, Naturheilkunde, Naturwissenschaft: Vom Monte Verità zur Molekularmedizin

“…Forscher wie Satchidananda Panda vom Scripps Institute erforschen das Zusammenspiel von Essen und Fasten sowie Licht und Tages-Nacht-Rhythmik [5,6] und haben erst kürzlich einen ersten Transkriptom-Atlas zu diesem Thema publiziert [7]. Die bedeutende Rolle der Ernährung wird durch den Megatrend der Mikrobiomforschung befeuert; unlängst zeigten die international sehr beachteten Arbeiten von Erin Segal, dass jede einzelne Mahlzeit, ihre Komponenten und auch die Lebensumgebung zu distinkten individuellen Änderungen des Mikrobioms und Metabolismus führen [8,9]. Schon wird sogar spekuliert, ob die probiotische Therapie in Zukunft die zunehmend schwierig gewordene antibiotische Therapie zu ersetzen vermag.…”