New research in mice adds to those concerns. The study suggests that sucralose and stevia, two widely used sweeteners, can alter the gut microbiome and gene activity in ways that may affect metabolic health. Some of these biological changes were also observed in later generations.

“We found it intriguing that despite the growing consumption of these additives, the prevalence of obesity and metabolic disorders such as insulin resistance has not declined,” said Dr. Francisca Concha Celume of the Universidad de Chile, lead author of the article in Frontiers in Nutrition. “This does not mean that sweeteners are responsible for these trends, but it raises the question of whether they influence metabolism in ways we do not yet fully understand.”

Testing Sucralose and Stevia Across Generations

Researchers began by dividing 47 male and female mice into three groups. One group received plain water, while the other two received water containing either sucralose or stevia. The doses were designed to resemble amounts that a person might reasonably consume as part of a normal diet.

The mice were then bred for two successive generations. Unlike the original animals, both later generations were given only plain water.

“Animal models allow us to control environmental conditions very precisely and to isolate the effect of a specific factor, such as a dietary compound, while also following several generations within a relatively short time,” explained Concha.

Tracking Blood Sugar, Gut Bacteria, and Gene Activity

Researchers tested each generation for oral glucose tolerance, a measure used to evaluate how effectively the body handles glucose and identify signs of insulin resistance, which is an important warning sign for diabetes.

They also collected fecal samples to examine changes in the gut microbiome and measure concentrations of short-chain fatty acids. These compounds are produced by gut bacteria and can influence biological processes related to gene regulation. Changes in their levels could therefore point to epigenetic effects that may be transmitted from parents to offspring.

Scientists think sweeteners may alter short-chain fatty acid production by disrupting normal gut microbiome function. Those disruptions could ultimately influence gene expression.

The team also measured the activity of five genes in the liver and intestines. The genes are involved in inflammation, the integrity of the gut barrier, and metabolism. By examining them, researchers hoped to identify possible epigenetic changes connected with gut function, inflammation, and metabolic health that could help explain some of the suspected negative effects of non-nutritive sweeteners.

Sucralose and Stevia Produced Different Effects

The two sweeteners did not affect the mice in exactly the same way, and their effects also shifted between generations.

Among first-generation offspring, signs of impaired glucose tolerance appeared only in males descended from mice that consumed sucralose. By the second generation, researchers found elevated fasting blood sugar in male descendants of the sucralose group and female descendants of the stevia group.

Mice that consumed either sweetener also developed more diverse fecal microbiomes, but they had lower levels of short-chain fatty acids. That pattern suggests their gut bacteria were producing fewer beneficial metabolites. Reduced short-chain fatty acid concentrations were also found in both subsequent generations.

The effects associated with sucralose were stronger and more persistent. Mice exposed to sucralose showed larger changes in the composition of their fecal microbiomes, including greater numbers of potentially pathogenic bacteria and fewer beneficial species.

Sucralose Changes Persisted Longer

Sucralose also appeared to increase the activity of genes linked to inflammation while reducing the activity of genes associated with metabolism. Those effects were still detectable two generations after the original exposure.

Stevia also altered gene expression, but the changes were weaker and did not persist beyond one generation.

“When we compared generations, these effects were generally strongest in the first generation and tended to decrease in the second generation,” said Concha. “Overall, the effects linked to sucralose were more consistent and persistent across generations.”

“The changes we observed in glucose tolerance and gene expression could be interpreted as early biological signals related to metabolic or inflammatory processes,” said Concha. “For example, the animals did not develop diabetes. Instead, what we observed were subtle changes in how the body regulates glucose and in the activity of genes associated with inflammation and metabolic regulation. It is possible that such changes could increase susceptibility to metabolic disturbances under certain conditions, such as a high-fat diet.”

What the Mouse Study Does and Does Not Show

The researchers caution that the findings show associations between sweetener exposure and changes in metabolic health, but they do not prove that the sweeteners directly caused all of the observed effects.

The results also come from mice, meaning the biological response to non-nutritive sweeteners may differ in humans.

“The goal of this research is not to create alarm, but to highlight the need for further investigation,” said Concha. “It may be reasonable to consider moderation in the consumption of these additives and to continue studying their long-term biological effects.”

Researchers at the University of Illinois Urbana-Champaign, Duke University, and the Chan Zuckerberg Biohub Chicago found that this cellular limbo appears to be driven by inflammation that disrupts RNA splicing, an essential step cells use to turn genetic instructions into working proteins.

The findings, published in Nature Communications, could point toward new ways to diagnose and potentially treat severe alcohol associated liver disease.

Why the Liver Stops Repairing Itself

The liver is unusual among major human organs because it can regenerate after significant damage or even partial removal. Under normal circumstances, surviving liver cells can temporarily change their identity, multiply, and then mature again to restore lost tissue.

That ability can break down in alcohol associated liver disease, which is the leading cause of liver-related mortality worldwide and is linked to roughly 3 million deaths each year.

“We knew that the liver stops functioning and stops regenerating in patients with alcohol-related hepatitis and cirrhosis, even when a patient has discontinued consuming alcohol, but we didn’t know why,” said U. of I. biochemistry professor Auinash Kalsotra, who co-led the study with Duke University School of Medicine professor Anna Mae Diehl. “The only real life-saving treatment option once a patient reaches the liver failure stage in those diseases is transplantation. But if we understood why these livers were failing, maybe we could intervene.”

Kalsotra and Diehl have spent years studying the molecular processes that allow the liver to rebuild itself. Their previous work showed that regenerating liver cells temporarily reprogram which genes they use.

To begin the repair process, mature liver cells revert toward a fetal-like progenitor state. Progenitor cells are less specialized cells that can divide and produce new tissue. After multiplying, the cells normally reverse that process and become mature, fully functioning liver cells again.

That earlier discovery led the researchers to ask what goes wrong with this regenerative cycle in alcohol associated liver disease.

Liver Cells Become Trapped in Limbo

The team compared healthy liver samples with liver tissue from people with alcohol associated hepatitis or cirrhosis. The diseased samples were obtained from Johns Hopkins University Hospital through an initiative supported by the National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health.

A striking pattern quickly emerged.

Cells in the diseased livers had started moving away from their mature state and toward the regenerative state, but they were unable to finish the transition. Instead, they remained trapped between the two.

“They are neither functional adult cells nor proliferative progenitor cells. Since they are not functioning, more pressure builds on the remaining cells. So they try to regenerate, and they’re all ending up in this unproductive quasi-progenitor state, and that’s what is causing liver failure,” said U. of I. graduate students Ullas Chembazhi and Sushant Bangru, the co-first authors of the study.

The result is a damaging cycle. As more cells enter this unproductive state, fewer remain available to carry out the liver’s normal work. The remaining healthy cells then face greater demands and attempt to regenerate, only to risk becoming trapped as well.

RNA Splicing Emerges as a Key Problem

To understand what was preventing the cells from completing regeneration, the researchers examined the proteins being produced inside liver cells as well as the RNA molecules carrying genetic instructions from DNA to the cellular machinery that builds those proteins.

RNA acts as an intermediary between the genetic code stored in DNA and the proteins that perform most of a cell’s work. Before many RNA molecules can be used, pieces of them must be cut and joined together in a process known as RNA splicing.

This editing step matters because different combinations of RNA segments can produce proteins with different functions or direct them to different locations inside a cell.

Instead of simply measuring the total amounts of RNA and protein, as many studies do, Kalsotra’s team used deep RNA sequencing and computational analysis to examine how RNA fragments were being spliced.

“In comparing the samples, we saw RNA was getting misspliced broadly in alcohol-related liver disease, across thousands of genes, and it was affecting major functions of proteins,” said Kalsotra, who also is affiliated with the Carl R. Woese Institute for Genomic Biology at Illinois.

The scale of the problem was substantial. Mis-splicing appeared across thousands of genes, potentially altering how important proteins function throughout damaged liver cells.

A Missing Protein May Help Explain the Damage

The researchers identified one possible driver of these widespread errors: low levels of a protein called ESRP2.

ESRP2 binds to RNA and helps ensure that it is spliced correctly. In alcohol damaged liver cells, the team found that ESRP2 was deficient.

The consequences were not limited to whether a protein was produced. In many cases, the RNA errors altered molecular instructions that tell proteins where inside the cell they need to go.

“Proteins function at a very specific place in the cell, and that is directed by sequences within the protein that take the protein to that particular spot. We found that, in many cases, the sequence that dictates where the protein localizes within a cell was misspliced. That’s why it was important that we did the multiple analyses we did,” said Kalsotra, also a member of the Chan Zuckerberg Biohub Chicago. “There was the same amount of RNA and protein, but the protein was not at the right place to function. Due to missplicing, key proteins that are required for productive liver regeneration were getting stuck in the cytoplasm, when they needed to be in the nucleus.”

The nucleus contains a cell’s DNA and plays a central role in regulating gene activity. The cytoplasm is the surrounding area where many other cellular processes occur. If proteins needed for regeneration remain in the cytoplasm rather than reaching the nucleus, they may be present in normal amounts but unable to perform their intended jobs.

Mouse Experiments Strengthen the ESRP2 Link

To test whether the loss of ESRP2 could actually contribute to the regeneration failure, the researchers studied mice lacking the gene that produces the protein.

Those animals developed patterns of liver injury and failed regeneration that resembled what the scientists observed in people with advanced alcohol related hepatitis.

That raised another important question: Why was ESRP2 reduced in the first place?

The researchers traced the problem back to inflammation.

When alcohol is processed by the liver, it can damage tissue and attract immune cells and liver support cells to the affected areas. According to the study, those cells released high levels of inflammatory factors and growth factors.

The researchers found that these signals suppress both the production and activity of ESRP2.

Blocking Inflammation Restored Normal Splicing

The team then tested whether interrupting one of those inflammatory signals could reverse the problem.

In laboratory cultures of liver cells, the researchers used a molecule that blocks the receptor for one inflammation-promoting factor. After treatment, ESRP2 levels recovered, and RNA splicing became more normal.

That result suggests the pathway could become a potential treatment target. Rather than attempting to replace damaged liver tissue directly, future therapies might try to interrupt the inflammatory signals that prevent cells from completing regeneration.

The researchers also see potential diagnostic uses. Abnormally spliced RNA molecules could potentially serve as biological markers that help identify or monitor alcohol associated liver disease.

“I’m hopeful these findings will become a launching pad for future clinical studies. We can use these mis-spliced RNAs as diagnostic markers or develop treatments that can curb the inflammation. And if we can correct the splicing defects, then maybe we can improve recovery and restore damaged livers,” Kalsotra said.

Research Team and Support

The research team also included U. of I. biochemistry graduate students Diptatanu Das and Subhashis Natua; U. of I. undergraduate students Katelyn Toohill, Ishita Purwar, and Anuprova Bhowmik; Brandon Peiffer and Zhaoli Sun from Johns Hopkins University School of Medicine; Aurelia Leona and Yogesh Goyal from Northwestern University and Rajesh Dutta from Duke University School of Medicine.

The National Institutes of Health, the Chan-Zuckerberg Biohub Chicago, the Duke Endowment and the Muscular Dystrophy Association supported this work. The National Institutes of Health supported this work through grants R01-AA010154, R01-HL126845, R21-HD104039, R01-AA010154, 5R01-DK077794, 1R56-DK1343340 and R24 AA025017.

Once operational, Roman will combine sharp infrared vision with an unusually wide view of the sky. That combination will allow astronomers to examine enormous regions of space while also looking far back into cosmic history. Among its primary goals are studying dark matter, dark energy, and worlds outside of our solar system, known as exoplanets. Its sweeping observations are also expected to support many discoveries beyond those central objectives.

“Roman is exactly the kind of success story we want to see across NASA,” said NASA Administrator Jared Isaacman. “Delivered ahead of schedule and on budget, this mission reflects more than a decade of dedication from the NASA workforce and our industry partners. Now, Roman will give us a new atlas of the universe, push the boundaries of discovery, and demonstrate what is possible when America’s space program pairs bold ambition with disciplined execution.”

Roman Begins Its Journey Into Deep Space

Controllers at NASA’s Goddard Space Flight Center in Greenbelt, Maryland, started receiving telemetry from Roman just seven minutes after launch. Falcon Heavy operated as planned and separated from the observatory 31 minutes after liftoff. After detaching from the rocket’s center core, the two boosters returned safely to the launch site, where they can be refurbished.

“Roman will be a discovery machine that will bring us closer than ever before to answering humanity’s most profound questions about our cosmic history,” said Nicky Fox, associate administrator for the Science Mission Directorate at NASA Headquarters in Washington. “With its large field of view and fast survey speeds, Roman will usher us into a new era of discovery and make the invisible visible, setting the foundation for humanity’s search for life beyond our solar system.”

During the first part of the mission, Roman communicates with controllers using the Near Space Network, a system of ground stations and relay satellites that handles tracking, telemetry, and commands. Roughly 70 minutes after launch, communications shift to NASA’s Deep Space Network, which will help guide the observatory toward the second Sun-Earth Lagrange point, or L2, about one million miles from Earth.

L2 is a region where the gravitational influences of the Sun and Earth allow spacecraft to maintain a relatively stable position with limited fuel use. Roman will first communicate through the Canberra Deep Space Communication Complex in Australia. Approximately six hours later, communications will transfer to the Madrid Deep Space Communication Complex in Spain and then to the Goldstone Deep Space Communication Complex in California. Together, these facilities will help maintain continuous contact with the spacecraft during its journey.

Key Systems Deploy After Launch

One hour and 23 minutes after launch, the Roman team confirmed that the observatory’s solar panels and lower instrument sun shade had deployed successfully.

Over the next several days, Roman’s high-gain antenna and visor-like deployable aperture cover will also deploy. Mission controllers will carry out the first of two course corrections, and Roman’s Coronagraph Instrument will be switched on.

The Coronagraph Instrument will demonstrate technology that could eventually be used by future missions such as NASA’s Habitable Worlds Observatory concept to directly photograph planets resembling Earth. Directly imaging such planets is extraordinarily difficult because a host star can be billions of times brighter than the planet orbiting it. A coronagraph helps by blocking much of the star’s light so that nearby planets become easier to detect. Roman will move that technology forward by capturing images of planets similar in size to Jupiter.

A 300 Megapixel View of the Cosmos

A few weeks into the journey, Roman’s main scientific instrument, the Wide Field Instrument, will be activated.

The instrument is a 300 megapixel infrared camera equipped with 18 4K detectors, each roughly the size of a saltine cracker. Those detectors will gather photons from distant astronomical objects and turn them into detailed panoramas of the cosmos.

Roman was designed to remain optically stable while rapidly moving from one observation to another. That means it can cover huge portions of the sky without lengthy pauses between observations. NASA says the telescope is designed to survey the universe about 1,000 times faster than the Hubble Space Telescope.

This speed is one of Roman’s defining advantages. Hubble can capture extremely detailed images of relatively small areas of the sky, while Roman is designed to combine similarly sharp views with a much larger field of view. That should allow astronomers to study enormous numbers of galaxies, stars, and planets in a fraction of the time previously required.

First Roman Images Expected in Early 2027

For the remainder of its three-month commissioning period, scientists and engineers will carefully test and calibrate Roman’s instruments. These procedures are designed to make sure the observatory is operating precisely before its full science program begins.

NASA expects to release Roman’s first images in early 2027.

Once science operations are underway, Roman will transmit about 1.4 terabytes of data to Earth every day. That is the highest daily data rate yet for a NASA astrophysics mission. The enormous volume of information will require more than traditional analysis alone.

Machine learning, artificial intelligence, and citizen scientists will help researchers search through Roman’s observations and identify potentially important discoveries. Astronomers can then investigate the most promising findings in greater detail.

“We’ve never been able to view the universe with eyes like Roman’s before,” said Julie McEnery, Roman’s senior project scientist at NASA Goddard. “There’s no telling what more we’ll know and have seen by this time next year.”

A Major New NASA Astrophysics Mission

Roman is the fourth primary NASA mission to launch aboard a Falcon Heavy rocket. Earlier this year, NASA’s Launch Services Program worked with SpaceX to move the launch date forward after the telescope was completed earlier than expected.

NASA Goddard manages the Roman mission, with participation from the agency’s Jet Propulsion Laboratory in Southern California; Caltech/IPAC in Pasadena, California; the Space Telescope Science Institute in Baltimore; and scientists from a range of research institutions.

The mission’s main industrial partners are BAE Systems Inc., L3Harris Technologies, and Teledyne Scientific & Imaging. International contributions also come from ESA, JAXA, the French space agency CNES (Centre National d’Études Spatiales), and the Max Planck Institute for Astronomy in Germany.