Body Clock Off-Schedule? Prebiotics May Help

Summary: Prebiotics can help stabilize sleep/wake patterns following circadian rhythm disruptions.

Source: University of Colorado

Whether it’s from jetting across time zones, pulling all-nighters at school or working the overnight shift, chronically disrupting our circadian rhythm—or internal biological clocks—can take a measurable toll on everything from sleep, mood and metabolism to risk of certain diseases, mounting research shows.

But a new University of Colorado Boulder study funded by the U.S. Navy suggests simple dietary compounds known as prebiotics, which serve as food for beneficial gut bacteria, could play an important role in helping us bounce back faster.

“This work suggests that by promoting and stabilizing the good bacteria in the gut and the metabolites they release, we may be able to make our bodies more resilient to circadian disruption,” said senior author Monika Fleshner, a professor of integrative physiology.

The animal study, published in the journal Brain, Behavior and Immunity, is the latest to suggest that prebiotics—not to be confused with probiotics found in fermented foods like yogurt and sauerkraut—can influence not only the gut, but also the brain and behavior.

Naturally abundant in many fibrous foods—including leeks, artichokes and onions—and in breast milk, these indigestible carbohydrates pass through the small intestine and linger in the gut, serving as nourishment for the trillions of bacteria residing there.

The authors’ previous studies showed that rats raised on prebiotic-infused chow slept better and were more resilient to some of the physical effects of acute stress.

For the new study, part of a multi-university project funded by the Office of Naval Research, the researchers sought to learn if prebiotics could also promote resilience to body-clock disruptions from things like jet lag, irregular work schedules or lack of natural daytime light—a reality many military personnel live with.

“They are traveling all over the world and frequently changing time zones. For submariners, who can be underwater for months, circadian disruption can be a real challenge,” said lead author Robert Thompson, a postdoctoral researcher in the Fleshner lab. “The goal of this project is to find ways to mitigate those effects.”

How a healthy gut may prevent jet lag

The researchers raised rats either on regular food or chow enriched with two prebiotics: galactooligosaccharides and polydextrose.

They then manipulated the rats’ light-dark cycle weekly for eight weeks—the equivalent of traveling to a time zone 12 hours ahead every week for two months.

Rats that ate prebiotics more quickly realigned their sleep-wake cycles and core body temperature (which can also be thrown off when internal clocks are off) and resisted the alterations in gut flora that often come with stress.

“This is one of the first studies to connect consuming prebiotics to specific bacterial changes that not only affect sleep but also the body’s response to circadian rhythm disruption,” said Thompson.

The study also takes a critical step forward in answering the question: How can simply ingesting a starch impact how we sleep and feel?

The researchers found that those on the prebiotic diet hosted an abundance of several health-promoting microbes, including Ruminiclostridium 5 (shown in other studies to reduce fragmented sleep) and Parabacteroides distasonis.

They also had a substantially different “metabolome,” the collection of metabolic byproducts churned out by bacteria in the gut.

This shows a sleeping man
The authors’ previous studies showed that rats raised on prebiotic-infused chow slept better and were more resilient to some of the physical effects of acute stress. Image is in the public domain

Put simply: The animals that ingested the prebiotics hosted more good bacteria, which in turn produced metabolites that protected them from something akin to jet lag.

Are supplements worthwhile?

Clinical trials are now underway at CU Boulder to determine if prebiotics could have similar effects on humans.

The research could lead to customized prebiotic mixtures designed for individuals whose careers or lifestyles expose them to frequent circadian disruption.

In the meantime, could simply loading up on legumes and other foods naturally rich in the compounds help keep your body clock running on time? It’s not impossible but unlikely, they say—noting that the rats were fed what, in human terms, would be excessive amounts of prebiotics.

Why not just ingest the beneficial bacteria directly, via probiotic-rich foods like yogurt?

That could also help, but prebiotics may have an advantage over probiotics in that they support the friendly bacteria one already has, rather than introducing a new species that may or may not take hold.

What about prebiotic dietary supplements?

“If you are happy and healthy and in balance, you do not need to go ingest a bunch of stuff with a prebiotic in it,” said Fleshner. “But if you know you are going to come into a challenge, you could take a look at some of the prebiotics that are available. Just realize that they are not customized yet, so it might work for you but it won’t work for your neighbor.”

About this circadian rhythm research news

Author: Lisa Marshall
Source: University of Colorado
Contact: Lisa Marshall – University of Colorado
Image: The image is in the public domain

Original Research: Closed access.
Ruminiclostridium 5, Parabacteroides distasonis, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms” by Monika Fleshner et al. Brain, Behavior and Immunity


Ruminiclostridium 5, Parabacteroides distasonis, and bile acid profile are modulated by prebiotic diet and associate with facilitated sleep/clock realignment after chronic disruption of rhythms

Chronic disruption of rhythms (CDR) impacts sleep and can result in circadian misalignment of physiological systems which, in turn, is associated with increased disease risk. Exposure to repeated or severe stressors also disturbs sleep and diurnal rhythms.

Prebiotic nutrients produce favorable changes in gut microbial ecology, the gut metabolome, and reduce several negative impacts of acute severe stressor exposure, including disturbed sleep, core body temperature rhythmicity, and gut microbial dysbiosis.

In light of previous compelling evidence that prebiotic diet broadly reduces negative impacts of acute, severe stressors, we hypothesize that prebiotic diet will also effectively mitigate the negative impacts of chronic disruption of circadian rhythms on physiology and sleep/wake behavior.

Male, Sprague Dawley rats were fed diets enriched in prebiotic substrates or calorically matched control chow. After 5 weeks on diet, rats were exposed to CDR (12 h light/dark reversal, weekly for 8 weeks) or remained on undisturbed normal light/dark cycles (NLD). Sleep EEG, core body temperature, and locomotor activity were recorded via biotelemetry in freely moving rats.

Fecal samples were collected on experimental days –33, 0 (day of onset of CDR), and 42. Taxonomic identification and relative abundances of gut microbes were measured in fecal samples using 16S rRNA gene sequencing and shotgun metagenomics. Fecal primary, bacterially modified secondary, and conjugated bile acids were measured using liquid chromatography with tandem mass spectrometry (LC-MS/MS).

Prebiotic diet produced rapid and stable increases in the relative abundances of Parabacteroides distasonis and Ruminiclostridium 5. Shotgun metagenomics analyses confirmed reliable increases in relative abundances of Parabacteroides distasonis and Clostridium leptum, a member of the Ruminiclostridium genus. Prebiotic diet also modified fecal bile acid profiles; and based on correlational and step-wise regression analyses, Parabacteroides distasonis and Ruminiclostridium 5 were positively associated with each other and negatively associated with secondary and conjugated bile acids. Prebiotic diet, but not CDR, impacted beta diversity.

Measures of alpha diversity evenness were decreased by CDR and prebiotic diet prevented that effect. Rats exposed to CDR while eating prebiotic, compared to control diet, more quickly realigned NREM sleep and core body temperature (ClockLab) diurnal rhythms to the altered light/dark cycle. Finally, both cholic acid and Ruminiclostridium 5 prior to CDR were associated with time to realign CBT rhythms to the new light/dark cycle after CDR; whereas both Ruminiclostridium 5 and taurocholic acid prior to CDR were associated with NREM sleep recovery after CDR.

These results support our hypothesis and suggest that ingestion of prebiotic substrates is an effective strategy to increase the relative abundance of health promoting microbes, alter the fecal bile acid profile, and facilitate the recovery and realignment of sleep and diurnal rhythms after circadian disruption.

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