Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet

Lopez, Diana E. Gutierrez; Lashinger, Laura M.; Weinstock, George M.; Bray, Molly S.

doi:10.1016/j.cmet.2021.03.015

Cited by 74 publications

(53 citation statements)

References 143 publications

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“…A balanced gut microbiome promotes health and microbial dysbiosis has been linked to metabolic diseases, colorectal cancer and gastrointestinal inflammation [12,[15][16][17]. Similar pathological consequences are associated with circadian rhythm disruption (reviewed by [18][19][20]), which also induces microbiota dysbiosis [10,11,13,14,21]. Consequently, we hypothesized that circadian regulation of microbiota composition and function may contribute to the host's GI health.…”

Section: Introductionmentioning

confidence: 99%

The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Heddes

Altaha

Niu

et al. 2021

Preprint

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Diurnal (i.e., 24-hour) oscillations of the gut microbiome have been described in various species including mice and humans. However, the driving force behind these rhythms remains less clear. In this study, we differentiate between endogenous and exogenous time cues driving microbial rhythms. Our results demonstrate that fecal microbial oscillations are maintained in mice kept in the absence of light, supporting a role of the hosts circadian system rather than representing a diurnal response to environmental changes. Intestinal epithelial cell-specific ablation of the core clock gene Bmal1 disrupts rhythmicity of microbiota. Targeted metabolomics functionally link intestinal clock-controlled bacteria to microbial-derived products, in particular branched-chain fatty acids and secondary bile acids. Microbiota transfer from intestinal clock-deficient mice into germ-free mice altered intestinal gene expression, enhanced lymphoid organ weights and suppressed immune cell recruitment. These results highlight the importance of functional intestinal clocks for circadian microbiota composition and function, which is required to balance the hosts gastrointestinal homeostasis.

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Section: Introductionmentioning

confidence: 99%

The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Heddes

Altaha

Niu

et al. 2021

Preprint

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“…Our data also build upon previous findings that indicate nutritional status and feeding-associated cues potently alter the magnitude of IgA secretion and microbiota-associated oscillations. Indeed, both long-term undernutrition or chronic overnutrition can alter the generation of IgA responses in the intestinal tract, suggesting a dynamic interplay between nutrition, circadian rhythms and mucosal antibody responses and hostcommensal mutualism (9,14,15,20,21,23,25,28,29). More broadly, these findings suggest circadian IgA regulation of the microbiota may act to promote mutualism, metabolite availability and metabolic health, which together with recent advances (49), suggest IgA acts to determine host exposure to microbially-derived metabolites.…”

Section: Discussionmentioning

confidence: 93%

“…While cell-intrinsic circadian clocks are important for driving oscillatory immune cell activity, additional exogenous signals can act to entrain these circadian rhythms -most notably feeding cues (20,28). Moreover, emerging evidence suggests IgA responses are highly sensitive to changes in nutrition and diet (9,14,15,29).…”

Section: Feeding-associated Metabolic Cues Determine the Magnitude And Rhythmicity Of Intestinal Iga Responsesmentioning

confidence: 99%

Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Penny

Domingues

Krauss

et al. 2021

Preprint

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Mutualistic interactions with the commensal microbiota are enforced through a range of immune responses that confer metabolic benefits for the host and ensure tissue health and homeostasis. Immunoglobulin (Ig)A responses directly determine the composition of commensal species that colonize the intestinal tract but require significant metabolic resources to fuel antibody production by tissue-resident plasma cells. Here we demonstrate IgA responses are subject to diurnal regulation by dietary-derived metabolic cues and a cell-intrinsic circadian clock. Rhythmicity in IgA secretion conferred oscillatory patterns on the commensal microbial community and its associated metabolic activity, resulting in changes to metabolite availability over the course of the circadian day. Our findings suggest circadian networks comprising intestinal IgA, the diet and the microbiota align to ensure metabolic health.

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“…While cell-intrinsic circadian clocks are important for driving oscillatory immune cell activity, additional exogenous signals can act to entrain these circadian rhythms - most notably feeding cues ( 22 , 29 ). Moreover, emerging evidence suggests IgA responses are highly sensitive to changes in nutrition and diet ( 9 , 16 , 17 , 30 ).…”

Section: Resultsmentioning

confidence: 99%

Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism

et al. 2022

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Interactions between the mammalian host and commensal microbiota are enforced through a range of immune responses that confer metabolic benefits and promote tissue health and homeostasis. Immunoglobulin A (IgA) responses directly determine the composition of commensal species that colonize the intestinal tract but require substantial metabolic resources to fuel antibody production by tissue-resident plasma cells. Here, we demonstrate that IgA responses are subject to diurnal regulation over the course of a circadian day. Specifically, the magnitude of IgA secretion, as well as the transcriptome of intestinal IgA + plasma cells, was found to exhibit rhythmicity. Oscillatory IgA responses were found to be entrained by time of feeding and were also found to be in part coordinated by the plasma cell–intrinsic circadian clock via deletion of the master clock gene Arntl . Moreover, reciprocal interactions between the host and microbiota dictated oscillatory dynamics among the commensal microbial community and its associated transcriptional and metabolic activity in an IgA-dependent manner. Together, our findings suggest that circadian networks comprising intestinal IgA, diet, and the microbiota converge to align circadian biology in the intestinal tract and to ensure host-microbial mutualism.

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Circadian rhythms and the gut microbiome synchronize the host’s metabolic response to diet

Cited by 74 publications

References 143 publications

The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

The intestinal circadian clock drives microbial rhythmicity to maintain gastrointestinal homeostasis

Rhythmicity of Intestinal IgA Responses Confers Oscillatory Commensal Microbiota Mutualism

Rhythmicity of intestinal IgA responses confers oscillatory commensal microbiota mutualism

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