Can't sleep? Prebiotics could help
Dietary compounds found to influence gut metabolites, buffering stress
March 3, 2020
Science Daily/University of Colorado at Boulder
New research shows that animals on a prebiotic diet sleep better and are buffered from the physiological impacts of stress. The undigestible dietary compounds, found in fibrous foods and some dairy products, serve as nourishment for beneficial bacteria and influence metabolites that, in turn, impact the brain.
Specific fibers known as prebiotics can improve sleep and boost stress resilience by influencing gut bacteria and the potent biologically active molecules, or metabolites, they produce, new University of Colorado Boulder research shows.
The research could ultimately lead to new approaches to treating sleep problems, which affect 70 million Americans.
"The biggest takeaway here is that this type of fiber is not just there to bulk up the stool and pass through the digestive system," said Robert Thompson, a postdoctoral researcher in the Department of Integrative Physiology and lead author of the study, published today in the journal Scientific Reports. "It is feeding the bugs that live in our gut and creating a symbiotic relationship with us that has powerful effects on our brain and behavior."
Food for our bugs
Most people are familiar with probiotics, friendly bacteria present in fermented foods like yogurt and sauerkraut. More recently, scientists have taken an interest in prebiotics -- dietary compounds that humans cannot digest but serve as nourishment for our microbiome, or the trillions of bacteria residing within us. While not all fibers are prebiotics, many fibrous foods like leeks, artichokes, onions and certain whole grains are rich in them.
For the study, the researchers started adolescent male rats on either standard chow or chow infused with prebiotics and tracked an array of physiological measures before and after the rats were stressed.
As reported in the researchers' previous study, those on the prebiotic diet spent more time in restorative non-rapid-eye-movement (NREM) sleep. After stress, they also spent more time in rapid-eye-movement (REM) sleep, which is believed to be critical for recovery from stress.
While rats eating standard chow saw an unhealthy flattening of the body's natural temperature fluctuations and a drop in healthy diversity of their gut microbiome after stress, those fed prebiotics were buffered from these effects.
The new study sheds light on how prebiotics can help bust stress.
"We know that this combination of dietary fibers helps promote stress robustness and good sleep and protects the gut microbiome from disruption. With this new study, we wanted to try to identify the signal," said senior author and Integrative Physiology Professor Monika Fleshner, director of the Stress Physiology Laboratory.
Using a technology called mass spectrometry to analyze the rats' fecal samples, the researchers measured metabolites, or bioactive small molecules produced by bacteria as food is broken down.
They found rats on the prebiotic diet had a substantially different "metabolome," or make-up of metabolites. Theirs was higher in dozens of them, including fatty acids, sugars and steroids which may, via gut-brain signaling pathways, influence behavior. The rats' metabolome also looked different after stress.
For instance, the rats on the standard chow diet saw dramatic spikes in allopregnanolone precursor and Ketone Steroid, potentially sleep-disrupting metabolites, while those on the prebiotic diet saw no such spike.
"Our results reveal novel signals that come from gut microbes that may modulate stress physiology and sleep," said Fleshner.
In search of a better sleeping pill
While prebiotic dietary fiber is certainly healthy, it's uncertain whether just loading up on foods rich in it can promote sleep. The rats were fed very high doses of four specific prebiotics, including: galactooligosaccharides, which are present in lentils and cabbage; polydextrose (PDX) an FDA-approved food additive often used as a sweetener; lactoferrin, found in breast milk; and milk fat globular protein, abundant in dairy products.
"You'd probably have to eat a whole lot of lentils and cabbage to see any effect," said Thompson.
Prebiotic supplements already abound on natural food store shelves. But Fleshner said it's too soon to say whether a supplement or drug containing such compounds would be safe and effective for everyone. Depending on what their microbial make-up is, different people might respond differently.
"These are powerful molecules with real neuroactive effects and people need to exercise some caution," she said.
Human studies are already in the works at CU Boulder.
Ultimately, Fleshner believes what they are learning in her lab could lead to a new class of options for people who can't sleep but don't like taking narcotics.
"Armed with this information, we might be able to develop a targeted therapeutic that boosts the molecules that buffer against stress and tamps down the ones that seem to disrupt sleep," she said. "It's exciting to think about."
https://www.sciencedaily.com/releases/2020/03/200303155658.htm
Sugar alters compounds that impact brain health in fruit flies
September 6, 2019
Science Daily/University of Michigan
When fruit flies are exposed to a high sugar diet, key metabolites associated with brain health become depleted, according to a University of Michigan study.
This finding could tell researchers why behaviors that change with the internal energy state, such as food intake, learning and memory, and sleep, change on high-nutrient diets.
When our bodies metabolize food, that food is broken down into metabolites -- small molecules that perform many functions in the body, including providing fuel to cells and activating or inhibiting enzyme production. The study, published in Nature Communications, examines how metabolites in the brains and bodies of fruit flies change as the flies transition between hunger and satiety.
Through the study, the researchers found that the flies' metabolic profiles change rapidly during the quick transition from hunger to satiety, with the flies' brains showing a larger change than their bodies. In particular, the high sugar diet lowered the levels the brain metabolites N-acetyl aspartate, or NAA, and kynurenine.
The alteration of metabolites could impact how quickly the fly senses satiety, causing it to eat more. In fact, U-M researchers previously found that an increase in a specific metabolite with a high sugar diet caused overeating and weight gain.
Although scientists aren't clear on the role of NAA in the brain, it appears to provide fuel for brain cells and balances osmolarity -- or regulates cell volume -- in the brain. Lower levels of another metabolite, kynurenine, which is produced in high levels during exercise, is associated with depression.
"What we found was a metabolic remodeling," said senior author Monica Dus, U-M assistant professor of molecular, cellular and developmental biology. "It wasn't just a gradual accumulation from an early to longer exposure, but by the seventh day on a high sugar diet, these fruit flies had a completely different metabolic profile."
Cancer cells also undergo this type of metabolic remodeling in order to fuel their growth, which is why diet may play a role in cancer treatment and a reason the Dus lab wanted to examine the shift of metabolites in the brain.
To examine how a high sugar diet affects the brains and bodies of fruit flies, the research team compared a group of fasting flies to a group of fed flies. In the fed flies, the researchers skipped giving them dinner, then fed them a breakfast of moderately sweet glucose jelly the next day.
The researchers mix the sugar jelly with blue or green dye, and after an hour, check the belly of the fly to make sure it's eaten. To make sure the animals have eaten their fill, the researchers put the flies on a lickometer covered with the glucose jelly. A lickometer is exactly what it sounds like: A meter that counts the number of times it has been licked.
Then, inside separate tubes, researchers freeze the sated flies as well as the group of fasting flies. This stops the metabolic process, so that researchers can look at what's going on in the flies' brains at the moment of satiety. The researchers shake the tubes, which shatters the fly. A sieve separates the fly's head, thorax, abdomen and legs. These parts were then sent to a company that uses mass spectrometry to measure the metabolites within the fly.
To help refine the list of metabolites in the flies, Alla Karnovsky, a research associate professor of computational medicine and bioinformatics at Michigan Medicine, created a tool called FlyScape. She based it on a previous tool she created for the analysis of human metabolomics data called MetScape. Like Metscape, Flyscape is open access: any researcher studying metabolites in fruit flies can use the software.
These tools help researchers look for patterns in metabolomics data. A researcher like Daniel Wilinski, a postdoctoral fellow in the Dus lab and first author of the manuscript, can input a list of metabolites found in her fruit fly subjects, as well as a list of genes from fruit flies, into Flyscape. The tool will produce visualizations of the metabolic networks of fruit flies.
"You can view the metabolites and genes that are changing between different conditions," Karnovsky said. "This helps us understand what biological processes are happening."
Co-author Peter Freddolino, assistant professor of biological chemistry and computational medicine and bioinformatics at Michigan Medicine, has worked with Dus on previous papers to study how a high sugar diet dulls the sense of taste in fruit flies.
"We examined what the changes in metabolites are that could be fundamentally perturbing the way that these cells were working," Freddolino said. "What this study tells us is what metabolomic pathways might be involved."
Ultimately, the study found that 20 metabolites, in addition to NAA and kynurenine, were impacted by sugar consumption. Next, says Dus, the research team plans to dial down into how changes in these metabolites impact the brain, altering food intake and affecting other conditions such as sleep, learning and memory.
https://www.sciencedaily.com/releases/2019/09/190906090559.htm