39 Sweeteners Put to the Test Produced Surprising Gut Changes

 Scientists found that sweeteners can behave unexpectedly inside a simulated gut, especially when combined with common medications.

Cambridge researchers have found that many widely used sweeteners can directly slow or alter the growth of bacteria found in the human gut. The strongest effect appeared when isosteviol, a sweetener used in foods and beverages, was combined with the antidepressant duloxetine.

In laboratory experiments, that combination sharply reduced two important bacterial species associated with digestive health and blood sugar regulation. It also produced changes that could influence inflammation and immune activity.

The researchers caution that the findings come from controlled laboratory tests, not studies involving people. More work will be needed to determine whether the same interactions occur inside the human body and whether they have meaningful health consequences.

Sweeteners May Not Be Biologically Inactive

Sweeteners are found in a wide range of everyday products, including soft drinks, candy, desserts, snacks, cereals, and some medications. They are often promoted as alternatives that provide sweetness with less sugar or fewer calories.

However, growing evidence has linked the consumption of some sweeteners with conditions including type 2 diabetes, obesity, and cancer. These associations do not necessarily prove that sweeteners directly cause those diseases, but they have raised questions about how the compounds behave inside the body.

One possible link is the gut microbiome, the enormous community of bacteria and other microorganisms living throughout the digestive tract. These microbes help break down food, produce useful compounds, support the intestinal barrier, and communicate with the immune system.

Despite the widespread use of sweeteners, relatively few studies have examined whether they interact directly with individual gut bacteria.

Professor Kiran Patil from the Medical Research Council (MRC) Toxicology Unit at the University of Cambridge said: “Most of what we know about the potential impact of sweeteners on our health comes from animal research or from population studies. While these studies have indicated involvement of the microbiome in mediating the effect of sweeteners, it’s difficult to know how sweeteners act in the body – is it through direct interactions with our gut bacteria?”

“Answering this is further complicated by the fact that we rarely ever take sweeteners by themselves – we take them with drinks, in snacks, or even in medication to mask bitterness,” added Dr. Sonja Blasche, a lead author of the study, also the MRC Toxicology Unit.

Researchers Tested 39 Common Sweeteners

For the study, published in Molecular Systems Biology, Dr. Blasche and her colleagues investigated how artificial and low-calorie sweeteners affect gut bacteria under laboratory conditions. They also examined whether those effects changed when the sweeteners were mixed with other substances commonly consumed at the same time.

The team grew 25 bacterial species individually. The collection included microbes considered beneficial, neutral, or potentially harmful.

Each bacterial culture was then exposed to 39 commercially used sweeteners, including both natural and artificial varieties. The researchers measured whether the bacteria continued multiplying normally, grew more slowly, or stopped growing.

About three-quarters of the sweeteners altered the growth of at least one bacterial species. Some significantly slowed or completely halted the growth of microbes associated with a healthy gut.

More Than 100 Hidden Interactions

People rarely consume sweeteners in isolation, so the scientists next combined them with other common compounds. These included caffeine, vanillin (vanilla extract), advantame (an artificial sweetener), and eight widely used medications.

The results revealed more than 100 interactions in which a sweetener affected bacteria differently when another compound was present. In 34 cases, the second substance strengthened the sweetener’s effect. In 68 cases, it weakened the effect.

This suggests that the biological impact of a sweetener may depend partly on what is eaten, drunk, or taken with it.

One Sweetener and Antidepressant Stood Out

The most dramatic response involved isosteviol and duloxetine. Isosteviol is used in the food and beverage industry, while duloxetine is prescribed for depression and several other conditions.

Together, the two compounds strongly suppressed Roseburia intestinalis and Parabacteroides merdae. Both bacteria are associated with functions that help maintain digestive and metabolic health.

Duloxetine is also widely prescribed. In the US in 2023, more than 4.2 million patients received the medication.

Source: ScitechDaily

Where You Live May Shape Your Dementia Risk More Than Scientists Realized

 A major global study found that the leading modifiable risk factors for dementia vary significantly from one country to another, challenging the idea of a universal prevention plan.

A large international study led by USC has found that the most common preventable or manageable risk factors for dementia differ sharply around the world. The analysis included more than 214,000 older adults from 14 countries and regions and examined factors such as limited education, high blood pressure, and smoking.

The results suggest that dementia prevention cannot rely on the same strategy everywhere. The risks that affect the greatest number of people in one country may be far less common in another.

The findings were presented at the Alzheimer’s Association International Conference 2026 in London and published in The Lancet Healthy Longevity. AAIC is the largest international gathering devoted to dementia research.

Expanding Dementia Research Beyond Wealthy Countries

Much of the existing evidence about dementia prevention comes from studies conducted in wealthier nations, particularly the United States and countries in Western Europe. Researchers from USC, Brown University, and Johns Hopkins University wanted to determine whether the same risk patterns also appear in low- and middle-income countries.

Their analysis uncovered major differences between populations, along with some unexpected similarities.

Low education affected 85.6% of older adults in China, compared with only 12.0% in the United States. High BMI (a measure of excess body weight), by contrast, was found in 44.9% of participants in the United States but only 13.3% of those in India.

Despite these differences, certain risks frequently appeared together in similar combinations across the world. Cardiovascular problems, including high cholesterol and hypertension, often formed one cluster. Behaviors such as smoking and drinking commonly formed another.

Similar Risk Patterns Across Different Populations

Lead author Emma Nichols, a research scientist with the Center for Economic and Social Research at the USC Schaeffer Institute for Public Policy & Government Service, said these shared patterns were among the study’s most surprising results.

“I was less surprised by the differences and more surprised by some of the similarities, particularly in the ways these risks are patterned across settings,” Nichols said. “That has real implications for how we design prevention strategies and interventions, because some things are more consistent across places than we might expect.”

Click here for a graphic depicting differences and similarities in dementia risk across different countries.

Data From More Than 214,000 Older Adults

Researchers with the Gateway to Global Aging Data team brought together standardized survey information from long-running aging studies in 14 locations. These included the United States, England, Ireland, Northern Ireland, four regions of Europe, Korea, Mexico, China, Malaysia, Brazil, and India. The data were collected between 2009 and 2023. (Jinkook Lee of the Center for Economic and Social Research at the USC Schaeffer Institute is principal investigator of the Gateway to Global Aging Data project as well as the Longitudinal Aging Study in India.)

The team examined 12 modifiable dementia risk factors identified by the Lancet Commission on dementia. Modifiable risk factors are conditions or behaviors that may be changed or managed over time. The factors included hearing loss, depression, physical inactivity, and social isolation.

Researchers compared how frequently each risk appeared, how prevalence differed according to age, gender, and education, and how often several risks occurred in the same person.

Why Dementia Prevention Must Be Tailored

The findings could help governments, health systems, and other organizations create prevention programs that better match the needs of their populations.

For instance, a program designed to connect people with diabetes care could be expanded to address a broader group of related cardiometabolic risks, including hypertension and high cholesterol. Targeting several connected risks together may be more effective than treating each one separately.

The research also carries an encouraging message for individuals. Dementia risk is not necessarily fixed, and many contributing factors can be influenced throughout life.

“Risk for these late-life outcomes isn’t predetermined. These are risk factors you experience over the life course, and you can have an impact on changing your own risk — while also recognizing the ways broader societal factors shape that risk, too.”

Future Research Will Include More Countries

Future studies may examine newer potential risk factors, including poor sleep. Researchers also plan to add more countries as additional standardized data become available.

Source:Scitech Daily

Why AI May Never Reach Human Intelligence

 A new analysis argues that AI may never truly think like humans because the most important parts of human intelligence cannot be programmed into machines.

A prominent computer scientist argues that a proposal made by Alan Turing, widely regarded as the father of theoretical computer science, sent artificial intelligence research in the wrong direction for the past 75 years.

In his new analysis, “Turing’s Mistake: Escaping the Yoke of Unintelligent Machines,” Peter J. Denning examines ideas Turing advanced in 1950. At the time, many scientists believed that human intelligence could exist independently of the body and might therefore be recreated as software running on a digital computer.

Denning also disputes the idea that machine intelligence can be demonstrated through an imitation game (now known as the Turing test).

“These two claims have shaped much of AI research and development,” Denning writes. “My premise is that our acquiescence to these claims has led to the AI mess in which we find ourselves today.”

According to Denning, the artificial intelligence (AI) systems now being developed are unlikely to produce human-level intelligence, known as artificial general intelligence (AGI). Instead, he warns, they may create serious dangers without ever thinking like humans.

Why Tacit Knowledge Matters

Central to Denning’s argument is the idea of tacit knowledge. This refers to the enormous amount of human understanding that people possess but cannot fully express in words or translate into symbols that a machine can process.

Denning describes five broad forms of tacit knowledge that he says ‘elude machine learning’. They include common sense, everyday interactions with people and the environment, feelings and perceptions, practical skills, and the cultural and historical background shared by societies.

Researchers have spent decades trying to record common sense in a form computers can use. Beginning in the 1980s, Douglas Lenat’s ambitious Cyc project set out to build a vast database of common-sense facts. After 40 years of work, the project contained 25 million entries.

“Yet even this treasury could not add up to a background of common sense sufficient to make expert systems smart enough to be experts,” Denning notes. “Cyc validated that much of the knowledge that makes people experts cannot be articulated as propositions.”

Knowing What Is Not the Same as Knowing How

Practical skill creates another major obstacle, Denning argues.

“Our performance skills in thousands of domains cannot be communicated to machines,” Denning explains. “Whereas descriptions of skillful outcomes (‘know what’) can often be represented as bits and stored in a machine, we do not know how to encode the embodied knowledge for skillful performance (‘know how’).”

Music offers a clear example of this difference. Denning says: “A virtuoso violinist can play beautiful music yet cannot describe to an acolyte how to produce it.

“Even if a robot could observe and imitate skilled humans, having no biological body, a robot cannot grasp how the musician feels when playing beautiful music or how an audience feels when hearing it.”

Intuition, gut feelings, spontaneous creativity, and imagination are other forms of tacit knowledge that resist being reduced to computer instructions.

The Representation Problem

Denning calls the central obstacle ‘the representation problem’.

Computers can only perform calculations when data and instructions are encoded in physical forms they can recognize and process. Tacit knowledge, however, cannot easily be converted into such a format.

“Behind every word is a deep well of tacit knowledge that gives it meaning,” Denning says. “Words are but symbolic representations of meanings, not the meanings themselves. Commonly used Large Language Models, such as ChatGPT, Claude and Gemini only manipulate words, they cannot know or understand the meaning of what they are saying.”

This creates what Denning sees as an unbridgeable gap. Because scientists do not fully understand how tacit knowledge operates within humans, they cannot determine how to transfer it to a machine.

“How we host tacit knowledge is largely a mystery,” Denning admits. “All we know is that it is embodied. We have no idea what we might observe and measure in our bodies to reveal it.”

Why Context Changes Meaning

Denning also stresses the importance of context, or the surrounding circumstances that give human words and actions their meaning and purpose.

A statement can mean very different things depending on whether the speaker is sincere, sarcastic, angry, playful, or teasing. Context also helps people decide when to use humor, when to show tact, and how to interpret what someone leaves unsaid.

Source: ScitechDaily

Researchers Finally Solve a Decades-Old Mystery About Cellular Aging

 A new study identifies the molecular switch that determines when aging cells permanently stop dividing.

Every time a human cell divides, the tips of its chromosomes get a little shorter. Those tips, called telomeres, act like protective caps. Once they shrink too far, the cell treats the exposed chromosome ends as DNA damage and stops dividing for good.

That shutdown, known as replicative senescence, is one of the body’s built-in defenses against cancer. By forcing damaged or risky cells into permanent arrest, it can stop early cancer clones before they become full tumors. A new study in Molecular Cell now shows that this safety mechanism depends entirely on ATM kinase, a signaling protein that senses DNA breaks and helps protect genomic stability.

The work also helps explain a puzzle that has bothered cell biologists for decades. Cells grown in standard lab air, which contains far more oxygen than most tissues in the body, stop dividing sooner than cells kept at lower oxygen levels. According to the new findings, high oxygen makes ATM unusually reactive, causing cells to become less tolerant of short telomeres.

“Our results have illuminated the mechanism underlying the aging of human cells through replicative senescence,” says Titia de Lange, head of the Laboratory of Cell Biology and Genetics. “These insights are critical for understanding how this tumor suppression pathway prevents cancer.”

Creating the right conditions

Replicative senescence begins when telomeres can no longer recruit enough TRF2, a shelterin protein that helps hide chromosome ends from the DNA damage machinery. Without sufficient TRF2, telomeres start to look like broken DNA, setting off the signal that brings cell division to a halt.

This matters because short telomeres are not only a sign of cellular aging. They are also a warning that a cell may be entering dangerous territory. By stopping such cells from dividing, replicative senescence helps prevent early-stage cancers from expanding.

“Replicative senescence is a remarkably effective tumor suppressor pathway,” de Lange says. “We know this from patients with long telomeres in which this system does not work properly. These patients can get as many as five different cancers before the age of 70, indicating that in people with normal-length telomeres, the telomere tumor suppressor pathway prevents many cancers.”

Even so, the exact wiring of this cancer prevention system had remained unclear. Earlier studies suggested that either ATM or ATR, two major DNA damage signaling pathways, might be involved. Oxygen added another complication. Researchers had long known that cells cultured at about 20 percent oxygen reach senescence faster than cells grown at more body-like levels, roughly 1 to 8 percent oxygen. The obvious explanation, that high oxygen simply makes telomeres erode faster, had already been ruled out.

o solve the problem, de Lange and colleagues followed replicative senescence in primary human fibroblasts grown at either 3 percent or 20 percent oxygen. The lower oxygen condition was closer to what many cells experience inside the body, but it also made the experiments much more demanding. Even routine steps such as moving plates, adding reagents, or breaking open cells had to be done quickly to avoid exposing the samples to ordinary air.

“Any time the cells or the reagents are outside of the special low-oxygen incubator, they are exposed to 20 percent oxygen, which can change the molecular environment within minutes,” says Alexander Stuart, a former graduate student in the de Lange lab who now holds a postdoc position at Harvard. “That means you’re often in a race to do all the standard protocol steps extremely quickly so you can keep the samples at low oxygen as much as possible.”

Stuart found that ATM alone was responsible for enforcing senescence at both oxygen levels. When ATM was inhibited, or when TRF2 was overproduced, cells continued dividing past the point where they would normally stop. Blocking ATM signaling in already arrested cells also allowed them to resume growth, showing that the arrest was reversible and fully dependent on ATM.

The impact of high oxygen

The next question was why oxygen changed the timing of senescence so strongly. Stuart and de Lange found that high oxygen does not simply age cells faster in a general way. Instead, it puts ATM into a hyperactive state.

That difference changed how cells responded to extremely short telomeres. At 3 percent oxygen, cells could keep dividing even after many telomeres had become very short. When those same cells were shifted to 20 percent oxygen, ATM responded much more aggressively, treating the short telomeres as serious DNA damage and pushing the cells into senescence.

“I don’t think of it as low oxygen extending the lifespan of human cells—that’s the physiological state of our bodies. Rather, the question was: why do high oxygen conditions shorten cellular lifespan? One could then extend that question: why aren’t high oxygen conditions accurate systems for studying senescence?” Stuart says. “We’ve now shown that high oxygen represents a hyperactive ATM setting, which leads to fewer divisions than cells would naturally undergo.”

Source: SciTech Daily

Bridging diet, microbes, and metabolism: Implications for metabolic disorders

 Mounting evidence suggests that the secret to understanding human health and combating metabolic diseases lies hidden within the microscopic world of our gut bacteria. Recent research by scientists at the Boyce Thompson Institute (BTI) and Cornell University reveals that a specific fatty acid produced by gut bacteria directly influences fat metabolism in animals. This research is pivotal as it sheds light on the complex interplay between the diet, gut microbiota, and host metabolic health, offering insights that could open new avenues in our approach to managing metabolic disorders.

The researchers focused on certain gut bacteria that produce fatty acids with a special chemical structure, known as a cyclopropane ring, and showed that these can be converted into signals that turn on fat desaturation in the nematode C. elegans, a model organism often used to study human biology. Intriguingly, C. elegans itself produces a chemically similar fatty acid compound that regulates the same metabolic pathway as the bacterial cyclopropane fats.

"Our research suggests that the host organism may have acquired the ability to produce its own signaling molecule, mimicking bacterial biochemistry, through a gene obtained from bacteria -- a process known as horizontal gene transfer," shared Bennett Fox, a post-doctoral researcher at BTI and first author of the study.

The research, recently published in Nature Communications, showed that both the bacterial and endogenous fatty acids activate a host receptor that functions as a central regulator of overall fat metabolism. This direct link between microbiota metabolites and host lipid metabolism offers insight into how our bodies could harness beneficial gut bacteria to regulate vital processes like obesity and metabolic dysfunction.

"Microbiota-dependent metabolites regulate virtually every aspect of animal physiology, including development, metabolism, and immune responses. Despite the life-sustaining importance of these metabolites, many of their structures remain unknown," noted Frank Schroeder, a professor at BTI and senior author of the study.

The fact that chemicals produced by bacteria can influence the metabolism of their host is a promising area of research. Further studies can investigate host-bacterial interactions to better understand -- and potentially improve -- metabolic health.

"The devil is in the details. As we gain clarity regarding the molecular mechanisms of fat metabolism and its regulation by specific diet-derived compounds, we step closer to harnessing this knowledge for better health outcomes in humans," said Fox. "This research not only broadens our understanding of basic biological processes but also highlights potential pathways for future exploration in human health and disease management."

Want to learn more? Dr. Fox has prepared an in-depth synopsis of the research paper, Evolutionarily related host and microbial pathways regulate fat desaturation in C. elegans, available here.

This research was supported in part by the National Institutes of Health and the Howard Hughes Medical Institute.

Source: Sciencedaily

New research in fatty liver disease aims to help with early intervention

 A new study brings researchers closer to better understanding the pathology of the fatty liver disease MASH, which stands for metabolic dysfunction-associated steatohepatitis.

MASH is a consequence of poor diet and obesity and results in severe damage to the liver. In MASH, the liver becomes filled with active and rapidly multiplying T cells, which are a type of immune cell.

In today's study, published in Hepatology, researchers examine what these T cells look like and how they work in people with liver cirrhosis (a late stage of liver disease) and in an animal model of MASH.

"Our goal is to provide a more thorough understanding of the mechanisms that drive MASH. A better understanding can lead to people being diagnosed earlier or before the disease is at such a late stage that a liver transplant may be the only treatment option," said the paper's senior author Matthew Burchill, PhD, associate professor of medicine at the University of Colorado Anschutz Medical Campus.

MASH is a slow killer in that the progression of the disease takes place over the course of decades. Despite this, MASH is rapidly becoming the most prevalent liver disease worldwide. It's estimated that approximately 40 percent of the adult population in the United States is obese, and approximately 14 percent of asymptomatic middle-aged individuals in the US have biopsy proven MASH, according to a recent study in the Journal of Hepatology.

Burchill and his team found during MASH, T cells multiply and change in function in response to harmful substances associated with poor diet.

The study showed that like infections such as Hepatitis C virus, clonally expanded CD8+ T cells accumulate in the livers of both humans and mice with MASH. This suggests a potential role for antigen-activated CD8+ T cells in the pathogenesis of MASH.

"Understanding this process may help identify the specific substances that trigger T cell activation and growth in the liver during MASH. This understanding could eventually result in developing a biomarker test that will allow doctors to track and treat the disease progression before it's at a late stage," adds Burchill.

The study concludes that antigenic stimulation likely drives T cell accumulation and chronic exhaustion in MASH.

The authors mention that further studies are needed to understand the timing and persistence of antigen-driven T cell responses in the liver and their role in disease progression and resolution.

Source: ScienceDaily

This ultrasound treatment may help stop arthritis before it starts

 Researchers at The University of Alabama in Huntsville (UAH), part of The University of Alabama System, have identified a promising new use for continuous low-intensity ultrasound that could one day help treat joint injuries and reduce the risk of post-traumatic osteoarthritis. Their findings suggest the non-invasive approach may shift the body's immune response away from long-lasting inflammation and toward tissue repair, offering a potential drug-free strategy for improving healing.

The study, published in the Nature journal Scientific Reports, was led by Dr. Anuradha Subramanian, professor of chemical and materials engineering. It combined biological research conducted by Dr. Shahid Khan during his doctoral studies with computational and statistical analysis developed by Dr. Satyaki Roy, professor of mathematical sciences, along with contributions from graduate student Owen Trippany. The research was funded by the National Institutes of Health through an R01 grant awarded to Subramanian.

How Ultrasound Influences Immune Cells

The team focused on macrophages, specialized immune cells that play a key role in both inflammation and tissue repair, to understand how they respond to continuous low-intensity ultrasound.

"Following injury, the body recruits inflammatory 'defender' macrophages (M1) to clear damaged tissue and healer macrophages (M2) to support repair and recovery," Subramanian explains. "Persistent dominance of defender macrophages can create a prolonged inflammatory environment that contributes to post-traumatic osteoarthritis."

The researchers wanted to determine whether ultrasound could encourage these immune cells to transition from an inflammatory state to one that promotes healing.

"In an 'M1' state, microphages promote inflammation to fight damage or infection, but prolonged M1 activity can also harm healthy tissue," Subramanian notes. "In contrast, 'M2-like' macrophages support tissue repair and recovery. Shifting macrophages toward an M2-like state is important, because it may help reduce chronic inflammation while encouraging healing in damaged joints. Our findings suggest that continuous low-intensity ultrasound may help restore this balance by promoting a more reparative macrophage response."

Roy says chronic inflammation is a major factor in the development of post-traumatic osteoarthritis.

"Post-traumatic osteoarthritis is driven in part by persistent inflammation that limits tissue repair and accelerates joint degeneration," Roy adds. "Our team is interested in continuous low-intensity ultrasound because it offers a non-pharmacological, non-invasive approach that may help regulate immune cell behavior and promote a more reparative healing environment in injured joints."

A More Realistic Model of Joint Injury

To better recreate the conditions inside an injured joint, the researchers relied on fibronectin fragments, molecules generated as damaged tissue breaks down, instead of using only conventional laboratory methods to trigger inflammation. This approach produced a model that more closely reflects the biological environment that develops after a joint injury.

The team also combined transcriptomics, the large-scale study of gene activity, with an advanced computational method known as differential clustering. Rather than analyzing genes one by one, this technique identifies groups of genes whose behavior changes together, providing a broader picture of how immune cells respond to ultrasound treatment.

"This allowed us to study not only which genes changed, but also how groups of genes changed their coordinated behavior in response to ultrasound stimulation," Roy says.

Early Results Show Reduced Inflammation

The researchers found that continuous low-intensity ultrasound lowered biological markers linked to inflammation while increasing markers associated with a more reparative, M2-like macrophage state.

Although the research is still limited to laboratory experiments, the findings suggest that non-drug, non-invasive technologies could eventually be used to influence immune cell behavior and improve healing after joint injuries. The researchers believe the technique could become part of future treatments designed to slow the progression of osteoarthritis and improve recovery after joint trauma.

"The next steps will involve validating these findings in animal models of early post-traumatic osteoarthritis and studying how ultrasound-based modulation affects long-term tissue repair in joint injury settings," Subramanian says.

Source: ScienceDaily