Cancer cells prevent you from sleeping at night in order to survive

Cancer Overrides the Circadian Clock to Survive

Source: Medical University of South Carolina.

Tumor cells use the unfolded protein response to alter circadian rhythm, which contributes to more tumor growth, Hollings Cancer Center researchers at the Medical University of South Carolina (MUSC) find. A key part of the circadian clock opposes this process, according to a paper published online Dec. 11 in Nature Cell Biology.

For tumors to grow and spread, cancer cells must make larger than normal amounts of nucleic acids and protein, so they can replicate themselves. Yet in both normal and cancer cells that increase their synthesis of protein, a small percent of those proteins do not fold properly. When that happens, the cell activates its unfolded protein response (UPR), which slows down the making of new proteins while the misfolded proteins are refolded. Eventually, the buildup of misfolded proteins becomes toxic and leads to cell death. However, cancer cells have learned to use the UPR to slow protein synthesis when needed, in order to handle the backlog of misfolded proteins. This helps them survive in conditions that would kill normal cells.

This pattern of adaptation is often seen in tumor cells, according to J. Alan Diehl, Ph.D., the SmartState Endowed Chair in Lipidomics, Pathobiology and Therapy at the MUSC Hollings Cancer Center and senior researcher on the project. “What a tumor cell is doing is taking a pathway that’s already in the cell and using it to its advantage,” said Diehl.

Yet it was not clear exactly how cancer cells were able to use UPR activity to influence circadian rhythm. Diehl’s group found that the UPR and circadian rhythm are linked together to lead the clockwork of the cell and also that cancer cells use the UPR to manipulate the circadian clock in ways that allow them to survive conditions that are toxic to normal cells.

To start, Diehl and his fellow researchers formulated a new idea based on what was known about protein synthesis in the cell. First, as they knew, the UPR is altered in tumors, and second, cells establish a circadian rhythm to regulate metabolism by producing levels of certain proteins that rise and fall in coordination with natural cycles of light and dark. Third, other scientists had observed that circadian rhythm is altered in tumor cells. Since protein production is tied to circadian rhythm, Diehl’s group asked if misfolded proteins might change circadian rhythm in cancer cells.

In their first set of experiments, Diehl’s research team used chemicals to activate the UPR in osteosarcoma cells. They found that, when activated, the UPR changes levels of an important protein called Bmal1, which is a transcription factor that rises and falls with cycles of light and dark. As it does, it regulates the expression of major circadian rhythm genes. When cells were exposed to cycles of light and dark, Bmal1 levels peaked during dark hours. But when the UPR was chemically activated, Bmal1 stayed low during both light and dark phases, which caused a phase shift in the expression of circadian genes. When one of the main parts of the UPR machinery was absent in cells, the phase shift did not happen.

Next, the group found that the UPR functions much like a “middleman” between light-dark cycles and the ability of cells to establish a circadian rhythm from those cycles. Levels of the circadian protein Bmal1 continued to decrease, as the UPR was increasingly activated. In rodents that had their light-dark cycles suddenly reversed, Bmal1 stopped rising and falling – a clear sign that their circadian rhythms were disrupted. Shifts in light exposure activated the UPR in those rodents’ cells.

But what does that mean for the development of cancer? The team found that patients with breast, gastric or lung cancers survived longer when they had higher levels of Bmal1 protein. In myc-driven cancers, the UPR was causing the loss of Bmal1 protein, which caused the tumors to grow. Myc-driven tumors lost circadian rhythm, whereas normal cells maintained it. Conversely, high levels of Bmal1 overtook the UPR, thereby allowing protein synthesis to continue, which was toxic to tumor cells. In this way, Bmal1 directly encourages protein synthesis.

This is the first study showing that human cancer suppresses circadian rhythm by controlling protein synthesis through Bmal1. Cancer cells survived longer by using the UPR to suppress Bmal1 and short-circuit their circadian rhythms. These results are important for human biology, according to Yiwen Bu, Ph.D., a postdoctoral scholar in Diehl’s laboratory and first author on the paper. “Every single normal cell in our body has circadian oscillation,” said Bu. “We showed that resetting the circadian rhythms in cancer cells slows down their proliferation.”

Image shows a DNA strand.

Still, do changes in light-dark cycles contribute to the development of cancer in humans? It is not yet clear in patients if circadian shifts contribute to changes in the UPR and if that, in turn, contributes to the development of cancer. But these results could help clinicians boost the effectiveness of current cancer treatments, Diehl said.

“Physicians are beginning to think about timing delivery of therapies in such a way that, say, if we deliver a drug at a certain time of day, we’ll get better on-target effects on the cancer and less toxicity in the normal cells,” he said.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Heather Woolwine – Medical University of South Carolina
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “A PERK–miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival” by Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J. Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E. Armeson, Steven B. McMahon, Gerald B. Wertheim, Chi V. Dang, Davide Ruggero, Constantinos Koumenis, Serge Y. Fuchs & J. Alan Diehl in Nature Cell Biology. Published online December 11 2017 doi:10.1038/s41556-017-0006-y

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Medical University of South Carolina “Cancer Overrides the Circadian Clock to Survive.” NeuroscienceNews. NeuroscienceNews, 28 December 2017.
<http://neurosciencenews.com/cancer-circadian-clock-8241/&gt;.

Abstract

A PERK–miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival

The unfolded protein response (UPR) is a stress-activated signalling pathway that regulates cell proliferation, metabolism and survival. The circadian clock coordinates metabolism and signal transduction with light/dark cycles. We explore how UPR signalling interfaces with the circadian clock. UPR activation induces a 10 h phase shift in circadian oscillations through induction of miR-211, a PERK-inducible microRNA that transiently suppresses both Bmal1 and Clock, core circadian regulators. Molecular investigation reveals that miR-211 directly regulates Bmal1 and Clock via distinct mechanisms. Suppression of Bmal1 and Clock has the anticipated impact on expression of select circadian genes, but we also find that repression of Bmal1 is essential for UPR-dependent inhibition of protein synthesis and cell adaptation to stresses that disrupt endoplasmic reticulum homeostasis. Our data demonstrate that c-Myc-dependent activation of the UPR inhibits Bmal1 in Burkitt’s lymphoma, thereby suppressing both circadian oscillation and ongoing protein synthesis to facilitate tumour progression.

“A PERK–miR-211 axis suppresses circadian regulators and protein synthesis to promote cancer cell survival” by Yiwen Bu, Akihiro Yoshida, Nilesh Chitnis, Brian J. Altman, Feven Tameire, Amanda Oran, Victoria Gennaro, Kent E. Armeson, Steven B. McMahon, Gerald B. Wertheim, Chi V. Dang, Davide Ruggero, Constantinos Koumenis, Serge Y. Fuchs & J. Alan Diehl in Nature Cell Biology. Published online December 11 2017 doi:10.1038/s41556-017-0006-y

Time of Day Influences Susceptibility to Infection

Time of Day Influences Susceptibility to Infection

Summary: A new study reveals we are more susceptible to infections at certain times of the day as our circadian rhythm affects the ability of the virus to spread and replicate.

Source: University of Cambridge.

We are more susceptible to infection at certain times of the day as our body clock affects the ability of viruses to replicate and spread between cells, suggests new research from the University of Cambridge. The findings, published today in the Proceedings of the National Academy of Sciences, may help explain why shift workers, whose body clocks are routinely disrupted, are more prone to health problems, including infections and chronic disease.

When a virus enters our body, it hijacks the machinery and resources in our cells to help it replicate and spread throughout the body. However, the resources on offer fluctuate throughout the day, partly in response to our circadian rhythms – in effect, our body clock. Circadian rhythms control many aspects of our physiology and bodily functions – from our sleep patterns to body temperature, and from our immune systems to the release of hormones. These cycles are controlled by a number of genes, including Bmal1 and Clock.

To test whether our circadian rhythms affect susceptibility to, or progression of, infection, researchers at the Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, compared normal ‘wild type’ mice infected with herpes virus at different times of the day, measuring levels of virus infection and spread. The mice lived in a controlled environment where 12 hours were in daylight and 12 hours were dark.

The researchers found that virus replication in those mice infected at the very start of the day – equivalent to sunrise, when these nocturnal animals start their resting phase – was ten times greater than in mice infected ten hours into the day, when they are transitioning to their active phase. When the researchers repeated the experiment in mice lacking Bmal1, they found high levels of virus replication regardless of the time of infection.

“The time of day of infection can have a major influence on how susceptible we are to the disease, or at least on the viral replication, meaning that infection at the wrong time of day could cause a much more severe acute infection,” explains Professor Akhilesh Reddy, the study’s senior author. “This is consistent with recent studies which have shown that the time of day that the influenza vaccine is administered can influence how effectively it works.”

In addition, the researchers found similar time-of-day variation in virus replication in individual cell cultures, without influence from our immune system. Abolishing cellular circadian rhythms increased both herpes and influenza A virus infection, a dissimilar type of virus – known as an RNA virus – that infects and replicates in a very different way to herpes.

Dr Rachel Edgar, the first author, adds: “Each cell in the body has a biological clock that allows them to keep track of time and anticipate daily changes in our environment. Our results suggest that the clock in every cell determines how successfully a virus replicates. When we disrupted the body clock in either cells or mice, we found that the timing of infection no longer mattered – viral replication was always high. This indicates that shift workers, who work some nights and rest some nights and so have a disrupted body clock, will be more susceptible to viral diseases. If so, then they could be prime candidates for receiving the annual flu vaccines.”

As well as its daily cycle of activity, Bmal1 also undergoes seasonal variation, being less active in the winter months and increasing in summer. The researchers speculate that this may help explain why diseases such as influenza are more likely to spread through populations during winter.

Diagram of the circadian clock.

Using cell cultures, the researchers also found that herpes viruses manipulate the molecular ‘clockwork’ that controls our circadian rhythms, helping the viruses to progress. This is not the first time that pathogens have been seen to ‘game’ our body clocks: the malaria parasite, for example, is known to synchronise its replication cycle with the host’s circadian rhythm, producing a more successful infection.

“Given that our body clocks appear to play a role in defending us from invading pathogens, their molecular machinery may offer a new, universal drug target to help fight infection,” adds Professor Reddy.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: The research was mostly funded by the Wellcome Trust and the European Research Council.

Source: University of Cambridge
Image Source: This NeuroscienceNews.com image is for illustrative purposes only and is licensed CC BY SA 3.0.
Original Research: Abstract for “Cell autonomous regulation of herpes and influenza virus infection by the circadian clock” by Rachel S. Edgar, Alessandra Stangherlin, Andras D. Nagy, Michael P. Nicoll, Stacey Efstathiou, John S. O’Neill, and Akhilesh B. Reddy in PNAS. Published online August 15 2016 doi:10.1073/pnas.1601895113

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University of Cambridge. “Time of Day Influences Susceptibility to Infection .” NeuroscienceNews. NeuroscienceNews, 15 August 2016.
<http://neurosciencenews.com/infection-time-of-day-4848/&gt;.

Abstract

Cell autonomous regulation of herpes and influenza virus infection by the circadian clock

Viruses are intracellular pathogens that hijack host cell machinery and resources to replicate. Rather than being constant, host physiology is rhythmic, undergoing circadian (∼24 h) oscillations in many virus-relevant pathways, but whether daily rhythms impact on viral replication is unknown. We find that the time of day of host infection regulates virus progression in live mice and individual cells. Furthermore, we demonstrate that herpes and influenza A virus infections are enhanced when host circadian rhythms are abolished by disrupting the key clock gene transcription factor Bmal1. Intracellular trafficking, biosynthetic processes, protein synthesis, and chromatin assembly all contribute to circadian regulation of virus infection. Moreover, herpesviruses differentially target components of the molecular circadian clockwork. Our work demonstrates that viruses exploit the clockwork for their own gain and that the clock represents a novel target for modulating viral replication that extends beyond any single family of these ubiquitous pathogens.

“Cell autonomous regulation of herpes and influenza virus infection by the circadian clock” by Rachel S. Edgar, Alessandra Stangherlin, Andras D. Nagy, Michael P. Nicoll, Stacey Efstathiou, John S. O’Neill, and Akhilesh B. Reddy in PNAS. Published online August 15 2016 doi:10.1073/pnas.1601895113

Potassium rich foods in the afternoon and sodium rich foods in the morning for sleep

Mechanism that Controls When We Sleep and When We Wake Discovered

Simple 2-cycle mechanism turns key brain neurons on or off during 24-hour day.

Fifteen years ago, an odd mutant fruit fly caught the attention and curiosity of Dr. Ravi Allada, a circadian rhythms expert at Northwestern University, leading the neuroscientist to recently discover how an animal’s biological clock wakes it up in the morning and puts it to sleep at night.

The clock’s mechanism, it turns out, is much like a light switch. In a study of brain circadian neurons that govern the daily sleep-wake cycle’s timing, Allada and his research team found that high sodium channel activity in these neurons during the day turn the cells on and ultimately awaken an animal, and high potassium channel activity at night turn them off, allowing the animal to sleep. Investigating further, the researchers were surprised to discover the same sleep-wake switch in both flies and mice.

“This suggests the underlying mechanism controlling our sleep-wake cycle is ancient,” said Allada, professor and chair of neurobiology in the Weinberg College of Arts and Sciences. He is the senior author of the study. “This oscillation mechanism appears to be conserved across several hundred million years of evolution. And if it’s in the mouse, it is likely in humans, too.”

Better understanding of this mechanism could lead to new drug targets to address sleep-wake trouble related to jet lag, shift work and other clock-induced problems. Eventually, it might be possible to reset a person’s internal clock to suit his or her situation.

The researchers call this a “bicycle” mechanism: two pedals that go up and down across a 24-hour day, conveying important time information to the neurons. That the researchers found the two pedals — a sodium current and potassium currents — active in both the simple fruit fly and the more complex mouse was unexpected.

The findings were published today in the Aug. 13 issue of the journal Cell.

“What is amazing is finding the same mechanism for sleep-wake cycle control in an insect and a mammal,” said Matthieu Flourakis, the lead author of the study. “Mice are nocturnal, and flies are diurnal, or active during the day, but their sleep-wake cycles are controlled in the same way.”

When he joined Allada’s team, Flourakis had wondered if the activity of the fruit fly’s circadian neurons changed with the time of day. With the help of Indira M. Raman, the Bill and Gayle Cook Professor in the department of neurobiology, he found very strong rhythms: The neurons fired a lot in the morning and very little in the evening.

The researchers next wanted to learn why. That’s when they discovered that when sodium current is high, the neurons fire more, awakening the animal, and when potassium current is high, the neurons quiet down, causing the animal to slumber. The balance between sodium and potassium currents controls the animal’s circadian rhythms.

This image shows how light affects the suprachiasmatic nucleus in the circadian cycle.

Flourakis, Allada and their colleagues then wondered if such a process was present in an animal closer to humans. They studied a small region of the mouse brain that controls the animal’s circadian rhythms — the suprachiasmatic nucleus, made up of 20,000 neurons — and found the same mechanism there.

“Our starting point for this research was mutant flies missing a sodium channel who walked in a halting manner and had poor circadian rhythms,” Allada said. “It took a long time, but we were able to pull everything — genomics, genetics, behavior studies and electrical measurements of neuron activity — together in this paper, in a study of two species.

“Now, of course, we have more questions about what’s regulating this sleep-wake pathway, so there is more work to be done,” he said.

ABOUT THIS CIRCADIAN RHYTHM RESEARCH

In addition to Allada and Flourakis, other authors of the paper are Elzbieta Kula-Eversole, Tae Hee Han and Indira M. Raman, of Northwestern; Alan L. Hutchison, Aaron R. Dinner and Kevin P. White, of the University of Chicago; Kimberly Aranda and Dejian Ren, of the University of Pennsylvania; Devon L. Moose and Bridget C. Lear, of the University of Iowa; and Casey O. Diekman, of the New Jersey Institute of Technology.

Funding: The study was funded by the National Institutes of Health and Defense Advanced Research Projects Agency.

Source: Megan Fellman – Northwestern University
Image Source: The image is in the public domain
Original Research: Abstract for “A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability” by Matthieu Flourakis, Elzbieta Kula-Eversole, Alan L. Hutchison, Tae Hee Han, Kimberly Aranda, Devon L. Moose, Kevin P. White, Aaron R. Dinner, Bridget C. Lear, Dejian Ren, Casey O. Diekman, Indira M. Raman, and Ravi Alladac in Cell. Published online August 13 2015 doi:10.1016/j.cell.2015.07.036


Abstract

A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability

Highlights
•Rhythmic sodium leak conductance depolarizes Drosophila circadian pacemaker neurons
•NCA localization factor 1 links the molecular clock to sodium leak channel activity
•Antiphase cycles in resting K+ and Na+ conductances drive membrane potential rhythms
•This “bicycle” mechanism is conserved in master clock neurons between flies and mice

Summary
Circadian clocks regulate membrane excitability in master pacemaker neurons to control daily rhythms of sleep and wake. Here, we find that two distinctly timed electrical drives collaborate to impose rhythmicity on Drosophila clock neurons. In the morning, a voltage-independent sodium conductance via the NA/NALCN ion channel depolarizes these neurons. This current is driven by the rhythmic expression of NCA localization factor-1, linking the molecular clock to ion channel function. In the evening, basal potassium currents peak to silence clock neurons. Remarkably, daily antiphase cycles of sodium and potassium currents also drive mouse clock neuron rhythms. Thus, we reveal an evolutionarily ancient strategy for the neural mechanisms that govern daily sleep and wake.

“A Conserved Bicycle Model for Circadian Clock Control of Membrane Excitability” by Matthieu Flourakis, Elzbieta Kula-Eversole, Alan L. Hutchison, Tae Hee Han, Kimberly Aranda, Devon L. Moose, Kevin P. White, Aaron R. Dinner, Bridget C. Lear, Dejian Ren, Casey O. Diekman, Indira M. Raman, and Ravi Alladac in Cell. Published online August 13 2015 doi:10.1016/j.cell.2015.07.036

Gut Microbe Movements Regulate Host Circadian Rhythms

Summary: Study exposes a new dynamic between the mammalian organism and the microbes that live inside their gut.

Source: Cell Press.

Even gut microbes have a routine. Like clockwork, they start their day in one part of the intestinal lining, move a few micrometers to the left, maybe the right, and then return to their original position. New research in mice now reveals that the regular timing of these small movements can influence a host animal’s circadian rhythms by exposing gut tissue to different microbes and their metabolites as the day goes by. Disruption of this dance can affect the host. The study appears December 1 in Cell.

“This research highlights how interconnected the behavior is between prokaryotes and eukaryotes, between mammalian organisms and the microbes that live inside them,” says Eran Elinav, an immunologist at the Weizmann Institute of Science, who led the work with co-senior author Eran Segal, a computational biologist also at the Weizmann. “These groups interact with and are affected by each other in a way that can’t be separated.”

The new study had three major findings:

  • The microbiome on the surface layer of the gut undergoes rhythmical changes in its “biogeographical” localization throughout the day and night; thus, the surface cells are exposed to different numbers and different species of bacteria over the course of a day.
  • “This tango between the two partners adds mechanistic insight into this relationship,” Elinav says.
  • The circadian changes of the gut microbiome have profound effects on host physiology, and unexpectedly, they affect tissue that is far away from the gut, such as the liver, whose gene expression changes in tandem with the gut microbiome rhythmicity. “As such,” adds Elinav, “disturbances in the rhythmic microbiome result in impairment in vital diurnal liver functions such as drug metabolism and detoxification.”
  • The circadian rhythm of the host is deeply dependent on the gut microbiota oscillations. Although some circadian machinery in the host was maintained by its own internal clock, other components of the circadian clock had their normal rhythms destroyed. Most surprising, another set of genes in the host that normally exhibit no circadian rhythms stepped in and took over after the microbial rhythms were disrupted.

Previous work by Elinav and Segal revealed that our biological clocks work in tandem with the biological clocks in our microbiota and that disrupting sleep-wake patterns and feeding times in mice induced changes in the microbiome in the gut.

“Circadian rhythms are a way of adapting to changes in light and dark, metabolic changes, and the timing of when we eat,” says Segal. “Other studies have shown the importance of the microbiome in metabolism and its effect on health and disease. Now, we’ve shown for the first time how circadian rhythms in the microbiota have an effect on circadian rhythms in the host.”

Image shows a visual abstract for the research.

The investigators say their work has potential implications for human health in two important ways. First of all, because drugs ranging from acetaminophen to chemotherapy are metabolized in the liver, understanding — and potentially being able to manipulate — the circadian rhythms of our microbiota could affect how and when medications are administered.

Second, understanding more about this relationship could help to eventually intervene in health problems like obesity and metabolic syndrome, which are more common in people whose circadian rhythms are frequently disrupted due to shift work or jet lag.

“What we learned from this study is that there’s a very tight interconnectivity between the microbiome and the host. We should think of it now as one supraorganism that can’t be separated,” Segal says. “We have to fully integrate our thinking with regard to any substance that we consume.”

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Funding: This research was primarily funded by Yael and Rami Ungar, Israel; Leona M. and Harry B. Helmsley Charitable Trust; the Gurwin Family Fund for Scientific Research; Crown Endowment Fund for Immunological Research; estate of Jack Gitlitz; estate of Lydia Hershkovich; the Benoziyo Endowment Fund for the Advancement of Science; Adelis Foundation; John L. and Vera Schwartz, Pacific Palisades; Alan Markovitz, Canada; Cynthia Adelson, Canada; CNRS (Centre National de la Recherche Scientifique); estate of Samuel and Alwyn J. Weber; Mr. and Mrs. Donald L. Schwarz, Sherman Oaks; grants funded by the European Research Council; the German-Israel Binational foundation; the Israel Science Foundation; the Minerva Foundation; the Rising Tide foundation; the Alon Foundation scholar award; the Rina Gudinski Career Development Chair; and the Canadian Institute For Advanced Research (CIFAR).

Source: Joseph Caputo – Cell Press
Image Source: NeuroscienceNews.com image is credited to Thaiss et al/Cell 2016.
Original Research: Full open access research for “Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations” by Christoph A. Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A. Jaitin, Eyal David, Deborah R. Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren Shibolet, Zamir Halpern, Kenya Honda, Ido Amit, Eran Segal, and Eran Elinav for correspondence informationemail in Cell. Published online December 1 2026 doi:10.1016/j.cell.2016.11.003

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Cell Press “Gut Microbe Movements Regulate Host Circadian Rhythms.” NeuroscienceNews. NeuroscienceNews, 2 December 2026.
<http://neurosciencenews.com/cut-microbes-circadian-rhythm-5663/&gt;.

Abstract

Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations

Highlights
•Intestinal microbiota biogeography and metabolome undergo diurnal oscillations
•Circadian oscillations of serum metabolites are regulated by the microbiota
•Microbiota rhythms program the circadian epigenetic and transcriptional landscape
•The microbiota regulates the circadian liver transcriptome and detoxification pattern

Summary
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.

“Microbiota Diurnal Rhythmicity Programs Host Transcriptome Oscillations” by Christoph A. Thaiss, Maayan Levy, Tal Korem, Lenka Dohnalová, Hagit Shapiro, Diego A. Jaitin, Eyal David, Deborah R. Winter, Meital Gury-BenAri, Evgeny Tatirovsky, Timur Tuganbaev, Sara Federici, Niv Zmora, David Zeevi, Mally Dori-Bachash, Meirav Pevsner-Fischer, Elena Kartvelishvily, Alexander Brandis, Alon Harmelin, Oren Shibolet, Zamir Halpern, Kenya Honda, Ido Amit, Eran Segal, and Eran Elinav for correspondence informationemail in Cell. Published online December 1 2026 doi:10.1016/j.cell.2016.11.003