Non-nutritive sweeteners affect human microbiomes and can alter glycemic responses

Since the late 1800s non-nutritive sweeteners have promised to deliver all the sweetness of sugar with none of the calories. They have long been believed to have no effect on the human body, but researchers publishing in the journal Cell on August 19 challenge this notion by finding that these sugar substitutes are not inert, and, in fact, some can alter human consumers’ microbiomes in a way that can change their blood sugar levels.

In 2014, senior author Eran Elinav an immunologist and microbiome researcher at the Weizmann Institute of Science and the German National Cancer Center (DKFZ) and his team found that non-nutritive sweeteners affected the microbiomes of mice in ways that could impact their glycemic responses. The team was interested in whether these results would also be found in humans.

To address this important question, the research team carefully screened over 1300 individuals for those who strictly avoid non-nutritive sweeteners in their day-to-day lives, and identified a cohort of 120 individuals. These participants were broken into six groups: two controls and four who ingested well below the FDA daily allowances of either aspartame, saccharin, stevia, or sucralose.

“In subjects consuming the non-nutritive sweeteners, we could identify very distinct changes in the composition and function of gut microbes, and the molecules they secret into peripheral blood. This seemed to suggest that gut microbes in the human body are rather responsive to each of these sweeteners,” says Elinav. “When we looked at consumers of non-nutritive sweeteners as groups, we found that two of the non-nutritive sweeteners, saccharin and sucralose, significantly impacted glucose tolerance in healthy adults. Interestingly, changes in the microbes were highly correlated with the alterations noted in people’s glycemic responses.”

To establish causation, the researchers transferred microbial samples from the study subjects to germ-free mice — mice that have been raised in completely sterile conditions and have no microbiome of their own.

“The results were quite striking,” says Elinav. “In all of the non-nutritive sweetener groups, but in none of the controls, when we transferred into these sterile mice the microbiome of the top responder individuals collected at a time point in which they were consuming the respective non-nutritive sweeteners, the recipient mice developed glycemic alterations that very significantly mirrored those of the donor individuals. In contrast, the bottom responders’ microbiomes were mostly unable to elicit such glycemic responses,” he adds. “These results suggest that the microbiome changes in response to human consumption of non-nutritive sweetener may, at times, induce glycemic changes in consumers in a highly personalized manner.”

Elinav says that he expects the effects of the sweeteners will vary person to person because of the incredibly unique composition of our microbiome. “We need to raise awareness of the fact that non-nutritive sweeteners are not inert to the human body as we originally believed. With that said, the clinical health implications of the changes they may elicit in humans remain unknown and merit future long-term studies.”

“In the meantime, we need to continue searching for solutions to our sweet tooth craving, while avoiding sugar, which is clearly most harmful to our metabolic health,” says Elinav. “In my personal view, drinking only water seems to be the best solution.”

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Materials provided by Cell Press. Note: Content may be edited for style and length.

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Which animals can best withstand climate change?

Extreme weather such as prolonged drought and heavy rainfall is becoming more and more common as the global average temperature rises — and it will only get worse in the coming decades. How will the planet’s ecosystems respond?

“That is the big question and the background for our study,” said biologist John Jackson, who, together with his biologist colleagues Christie Le Coeur from the University of Oslo and Owen Jones from University of Southern Denmark, authored a new study, published in eLife.

John Jackson is now at Oxford University but was at the University of Southern Denmark when the study was made. Owen Jones is associate professor at the Department of Biology, University of Southern Denmark.

Llama, moose and elephant

In the study, the authors analyzed data on population fluctuations from 157 mammal species from around the world and compared them with weather and climate data from the time the animal data were collected. For each species there are 10 or more years of data.

Their analysis has given them an insight into how populations of animal species have coped at times of extreme weather: Did they become more, or less, numerous? Did they have more or fewer offspring?

“We can see a clear pattern: Animals that live a long time and have few offspring are less vulnerable when extreme weather hits than animals that live for a short time and have many offspring. Examples are llamas, long-lived bats and elephants versus mice, possums and rare marsupials such as the woylie,” said Owen Jones.

Less affected by extreme weather:

African elephant, Siberian tiger, chimpanzee, greater horseshoe bat, llama, vicuña, white rhinoceros, grizzly bear, American bison, klipspringer, Schreibers’s bat.

More affected by extreme weather:

Azara’s grass mouse, olive grass mouse, elegant fat-tailed mouse opossum, Canadian lemming, Tundra vole, Arctic fox, stoat, common shrew, woylie, arctic ground squirrel.

Quick drop — but also quick boom

Large, long-lived animals are better able to cope with conditions like prolonged drought; their ability to survive, to reproduce and to raise their offspring is not affected to the same extent as small, short lived animals. They can, for example, invest their energy into one offspring, or simply wait for better times when conditions become challenging.

On the other hand, small short-lived rodents have more extreme population changes in the short term. In the event of a prolonged drought, for example, large parts of their food base may disappear more rapidly: insects, flowers, fruits, and they are left to starve because they have limited fat reserves.

The populations of these small mammals may also boom to take advantage when conditions improve because, in contrast to large mammals, they can produce many offspring.

Not the same as risk of extinction

“These small mammals react quickly to extreme weather, and it goes both ways. Their vulnerability to extreme weather should therefore not be equated with a risk of extinction,” said John Jackson.

He also reminds us that the ability of an animal species to withstand climate change must not stand alone when assessing the species’ vulnerability to extinction:

“Habitat destruction, poaching, pollution and invasive species are factors that threaten many animal species — in many cases even more than climate change,” he emphasized.

The animals we don’t know much about

The researchers’ study not only gives an insight into how these specific 157 mammal species react to climate changes here and now. The study can also contribute to a better general understanding of how the planet’s animals will respond to ongoing climate change.

“We expect climate change to bring more extreme weather in the future. Animals will need to cope with this extreme weather as they always have. So, our analysis helps predict how different animal species might respond to future climate change based on their general characteristics — even if we have limited data on their populations,” said Owen Jones.

An example is the woylie, a rare Australian marsupial. Biologists do not know very much about this species, but because it shares a similar life style with mice — that is, it is small, lives for a short time and reproduces quickly — it can be predicted that it will respond to extreme weather in a similar way to mice.

Entire ecosystems will change

“In the same way, there are lots of animal species that we don’t know very much about, but whose reaction we can now predict,” explained John Jackson.

In this way, the researchers expect that the ability of different animal species to adapt to climate change is related to their life strategy, and this can help us predict ecological changes:

As habitat suitability changes due to climate change, species may be forced to move to new areas as old areas become inhospitable. These shifts depend on species’ life strategies and can have big impacts on ecosystem function.

The work has been supported by Independent Research Fund Denmark.

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Plasma-produced gas helps protect plants from pathogens

The flash of lightning and the dance of auroras contain a fourth state of matter known as plasma, which researchers have harnessed to produce a gas that may activate plant immunity against wide-spread diseases.

The team, based at Tohoku University in Japan, published their findings on June 24 in PLOS One.

“Currently, chemical pesticides are the mainstay of disease control in agriculture, but they can contaminate the soil and harm the ecosystem,” said paper author Sugihiro Ando, associate professor in the Graduate School of Agricultural Science at Tohoku University. “We need to develop plant disease control technologies that can help establish a sustainable agricultural system. The use of plant immunity is one of the most effective disease control methods because it utilizes the innate resistance of plants and has a low environmental impact.”

Using their previously developed device that derives plasma from the air, the researchers produced dinitrogen pentoxide, a reactive nitrogen species (RNS). This molecule is related to reactive oxygen species (ROS), in that both damage cells and trigger specific stress responses in organisms.

“It is well known that reactive species are important signaling factors in the immune response of plants, but the specific physiological function of dinitrogen pentoxide is poorly understood,” Ando said. “Plants produce reactive species as a defense response when they perceive an infectious stimulus from a pathogen. The generated reactive species function as signaling molecules that contribute to the activation of plant immunity.”

According to Ando, reactive species are linked to plant hormones such as salicylic acid, jasmonic acid and ethylene, which help regulate plant immunity, but the physiological function of dinitrogen pentoxide is poorly understand.

“Since reactive species are known to have important functions in plant immunity, we analyzed weather exposure of plants to dinitrogen pentoxide gas could enhance disease resistance,” Ando said.

The researchers exposed thale cress, a small plant commonly used as a model system for scientific research, to dinitrogen pentoxide gas for 20 seconds a day for three days. The plants were then infected with one of three common plant pathogens: a fungus, a bacterium or a virus. The plants with the fungus or the virus showed suppressed progression of the pathogen, while those with the bacterium had a similar proliferation as the control plants.

“These results suggest that the dinitrogen pentoxide gas exposure could control plant disease depending on the type of pathogen,” Ando said.

A genetic analysis revealed that the gas specifically activated the jasmonic acid and ethylene signaling pathways and appeared to lead to the synthesis of antimicrobial molecules, which Ando said may have contributed to the observed disease resistance. “Dinitrogen pentoxide gas can be used to activate plant immunity and control plant diseases,” Ando said. “Through plasma technology, the gas can be produced from air and electricity, without special materials. The gas can also be converted to nitric acid, when dissolved in water, and used as a fertilizer for plants. This technology can contribute to the construction of a sustainable agricultural system as a clean technology with minimal environmental impact.”

Next, the researchers plan to study how their technology works with crops and in greenhouse cultivation.

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Materials provided by Tohoku University. Note: Content may be edited for style and length.

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Early blood tests predict death, severe disability for traumatic brain injury

A study finds that blood tests taken the day of a traumatic brain injury can predict which patients are likely to die or survive with severe disability, allowing clinicians to make decisions earlier on possible treatment of TBI.

Researchers from Michigan Medicine, the University of California San Francisco and the University of Pennsylvania analyzed day-of-injury blood tests of nearly 1,700 patients with TBI. Results published in The Lancet Neurology reveal that higher values of two protein biomarkers, GFAP and UCH-L1, are associated with death and severe injury.

This is the first study to examine the association between biomarker levels of these two proteins and all-cause mortality following TBI, says first author Frederick Korley, M.D., Ph.D., associate professor of emergency medicine at the University of Michigan Medical School.

“Early and accurate prediction of TBI outcomes will help clinicians gauge how severe a brain injury is and inform how best to counsel family members about care for their loved ones with brain injury and what to expect with regards to their recovery,” Korley said. “It will also help researchers more precisely target promising TBI therapeutics to the right TBI patients.”

The U.S. Food and Drug Administration cleared the use of GFAP and UCH-L1 in 2018 to help clinicians decide whether to order CT scans for mild traumatic brain injury.

Researchers measured the proteins using two devices from Abbott Laboratories, the i-STAT Alinity and the ARCHITECT. Results were compared to evaluations made six months after injury using the Glasgow Outcome Scale-Extended, a system that grades the functional status of TBI patients.

Investigators found that compared to those with GFAP values in the bottom 20th percentile, those with GFAP values in the top 20th percentile had a 23 times higher risk of death during the subsequent six months. Similarly, compared to those with UCH-L1 values in the bottom 20th percentile, those with UCH-L1 values in the top 20th percentile had a 63 times higher risk of death during the subsequent 6 months.

“Modern trauma care can result in good outcomes in what we had once believed were non-survivable injuries,” said co-senior author Geoffrey Manley, M.D., Ph.D., professor and vice chair of neurosurgery at UCSF. “These blood tests are both diagnostic and prognostic, as well as easy to administer, safe and inexpensive.”

While the method is promising for determining poor outcomes in moderate and severe TBI, researchers say more must be done to examine its role in mild cases.

“As a next step, the TRACK-TBI team is planning a clinical trial that will examine the efficacy of promising therapeutic agents that may help traumatic brain injury patients recover quickly,” Korley said. “As part of this clinical trial, these biomarkers will be used as an objective method for selecting the right patients to enroll in this trial. We will also use these biomarkers to monitor individual patient response to these promising therapeutics.”

Korley previously consulted for Abbott Laboratories. Korley and Robertson have received research funding from Abbott Laboratories. Manley received research funding from a collaboration between Abbott Laboratories and the U.S. Department of Defense. Diaz-Arrastia consulted for MesoScale Discoveries, BrainBox Solutions, and NovaSignal. All other authors and collaborators declare no competing interests.

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Materials provided by Michigan Medicine – University of Michigan. Original written by Noah Fromson. Note: Content may be edited for style and length.

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