Day: May 7, 2026

Categories : Gastrointestinal NeurologyTags : Leave a comment

Head Impacts Associated with Altered Gut Microbiome in Football Players

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Non-concussive head impacts correlated with changes to the gut microbiome on following days, in pilot study tracking six US collegiate football players over one season

Image credit: Rich Barnes / Colgate Athletics, CC-BY 4.0 (https://creativecommons.org/licenses/by/4.0/)

Non-concussive head impacts – hits to the head that don’t cause clinically detectable symptoms – are correlated with subsequent changes to the gut microbiome in a small sample of US collegiate football players, according to a new study published May 6, 2026, in the open-access journal PLOS One by Ahmet Ay and Kenneth Douglas Belanger of Colgate University, USA, and colleagues.

Non-concussive head impacts are common in American football, with players experiencing between 100 and 1000 across a season. While research has shown that full concussions can disrupt the gut microbiome – which regulates inflammation and the neuroimmune system – whether sub-concussive hits might produce similar effects had not been investigated.

In the new study, researchers tracked six NCAA Division I American football players across a competition season, beginning during preseason training. Their on-field activity profiles were monitored using GPS units and head impacts were tracked using a helmet-based sensor system; 226 faecal samples were analysed for their microbiome composition; and participants completed lifestyle questionnaires after each sample collection.

The researchers found that microbial diversity changed within two to three days after a substantial head impact. Specifically, certain bacteria – including the order Coriobacteriales, the family Prevotellaceae, and the genus Prevotella – tended to decrease in abundance while the genus Ruminococcus increased. In previous studies, these changes have correlated with brain injury and inflammation.

The athletes’ gut microbiomes also changed significantly over the course of the season, with mathematical modelling suggesting that the cumulative effects of non-concussive head impacts was likely associated with this shift, even after accounting for 15 potentially confounding factors including diet changes, exercise intensity, sleep, and stress.

The study is limited by its small sample size and lack of a control group, with its design meaning findings could only establish correlation but not causation. However, the authors conclude that even sub-symptomatic head impacts might affect the gut microbiome, both in the immediate aftermath of injury and over a longer time course in athletes who experience multiple impacts. 

Ken Belanger adds: “As far as we are aware, this is the first study to examine connections between head impacts and the composition of the gut microbiome – the complex community of bacteria and other organisms within the digestive system.”

“Our results provide evidence that even head impacts that do not result in a concussion or other reported symptoms may influence the microbes present within the gut, both in the short- and longer-term. Determining what causes these changes and whether they have a positive or negative influence on recovery from head injury will require further investigation.”

“Our research highlights the importance of thinking integratively about the interactions between the gut and the brain. We are only beginning to scratch the surface in our understanding of how these complex organs and organ systems communicate with and affect each other.”

Aziz Zafar adds: “After having only heard of the complicated interplay between neuronal inflammation and the gut microbiome, I found it to be such an exciting scientific experience to explore that interplay in the context of head impacts.”

Zachary Pelland adds: “It has been an amazing privilege to work so deeply on a personally and scientifically meaningful project which could not have happened without immeasurable support across academic departments, athletics, administration, and alumni at Colgate University.” 

Provided by PLOS

Categories : Ageing Metabolic DisordersTags : Leave a comment

Choosing Safer Diabetes Medications for Older Adults

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Photo by Kampus Production

Older adults with type 2 diabetes face a difficult trade-off: they are among the most vulnerable to medication-related harms yet are often underrepresented in the clinical trials that guide treatment decisions. A new study led by Yuan Lu, ScD, helps address this gap by providing large-scale, real-world evidence about the safety of commonly used diabetes medications.

Published in Nature Communications, the study analysed data from more than 1.8 million people aged 65 and older across the United States and Europe. The researchers compared four major classes of second-line antihyperglycaemic medications – typically prescribed when first-line therapy such as metformin is not sufficient – across 18 safety outcomes.

“Evidence from clinical trials often does not fully capture older adults,” says Lu, assistant professor of medicine (cardiovascular medicine) at Yale School of Medicine. “They are more likely to experience side effects due to frailty, multiple chronic conditions, and the use of several medications at the same time.”

Newer diabetes drugs show overall safety advantages

The study found a consistent pattern: newer classes of medications, including GLP-1 receptor agonists and SGLT2 inhibitors, were generally associated with lower risks of several important adverse outcomes compared to older drugs such as sulfonylureas and DPP-4 inhibitors.

Newer agents were linked to lower risks of hypoglycaemia, hyperkalaemia, and peripheral oedema – complications that can be especially dangerous in older adults. However, the findings also highlight important trade-offs. For example, SGLT2 inhibitors were associated with a higher risk of diabetic ketoacidosis, while GLP-1 receptor agonists were more likely to cause gastrointestinal side effects such as nausea and vomiting.

Rather than identifying a single “best” medication, Lu emphasises that the results support more informed, individualised decision-making. “Some patients may have a higher risk of hypoglycaemia, while others may be more susceptible to diabetic ketoacidosis,” she says. “These risks need to be considered together as part of an individual patient profile.”

Real-world data at a global scale

A key strength of the study is its scale and approach. The analysis drew on nine large databases and was conducted through the Observational Health Data Sciences and Informatics (OHDSI), an international research network that enables standardized analyses across diverse health care systems.

By using harmonised real-world data and consistent analytic methods, the researchers were able to evaluate a broad range of safety outcomes in routine clinical practice – offering insights that complement and extend findings from randomised trials.

Supporting safer prescribing for an aging population

As the population ages and the use of newer diabetes medications continues to grow, understanding their safety profiles in older adults is increasingly important. The findings reinforce current guideline recommendations that often favour newer agents, while also underscoring the need to tailor treatment decisions to each patient’s risks and preferences.

Like all observational studies, the analysis cannot fully rule out unmeasured differences between patients. Still, the large, multinational design gives a more complete picture of medication safety in a population often underrepresented in clinical research.

Looking ahead, Lu and her colleagues hope to expand this work to examine the comparative safety of individual medications and to evaluate the safety of newer GLP-1 receptor agonists across a wider range of outcomes, including among people with obesity. “By providing more evidence in populations that clinicians see every day, our goal is to support safer, more informed care,” she says.

Source: Yale School of Medicine

Categories : CancerTags : Leave a comment

Drugging the Undruggable: A Million-fold Leap in Targeting Elusive Cancer Proteins

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Few medications can target disordered proteins, but new research outlines an enhanced approach that could lead to treatments for prostate cancer and other diseases

Photo by Louis Reed on Unsplash

Researchers at the University of British Columbia and BC Cancer have developed a new way to target proteins long considered ‘undruggable’, opening the door to new treatments for prostate cancer and other serious diseases.

Known as intrinsically disordered proteins, these molecular shapeshifters are extremely difficult to target with medication due to their flexible and ever-changing structure. They play a central role in a wide range of diseases, including cancer, neurodegenerative disorders, heart disease and autoimmune conditions, yet only a handful of medications currently exist that can target them.

In a study published today in Nature Signal Transduction and Targeted Therapy, the researchers demonstrate a new approach for designing drugs that bind more strongly to these proteins and block their disease-causing activity. In some cases, the compounds they developed bound up to a million times more tightly than any previously reported.

“This study shows that proteins previously thought to be undruggable can be drugged with remarkable efficacy,” said principal investigator Dr Marianne D. Sadar, professor of pathology and laboratory medicine at the UBC faculty of medicine and distinguished scientist at BC Cancer. “The findings could have profound implications for the treatment of cancer and other diseases, providing a roadmap for the development of new treatments.”

A long-standing challenge in drug discovery

Unlike most proteins, which fold into stable three-dimensional shapes, disordered proteins contain flexible regions that change as they interact with molecules inside cells. Because they lack fixed binding sites, they are extremely difficult to target with traditional drugs.

“Most drug discovery is like designing a key for a very specific lock,” said Dr Sadar. “But disordered proteins don’t behave like locks at all, they’re more like moving strands of spaghetti.”

Dr Sadar and her team have spent decades studying how to target these proteins. In 2008, they developed the first compound capable of binding to them, and have since advanced two such drugs into clinical trials – another world-first milestone for the field.

Despite these advances, achieving strong and consistent binding has remained a central challenge.

A new strategy against prostate cancer

The new study focused on a specific protein, the androgen receptor, which fuels the growth of most prostate cancers.

Rather than fitting into a single fixed spot, the researchers developed compounds that interact with the moving region of the protein, freeze it in an inactive state, and prevent it from turning on genes that drive cancer growth.

“It’s a major achievement. Our target drugs had binding affinity a million times greater than existing drugs targeting these regions,” said Dr Natalie Strynadka, professor of biochemistry and molecular biology at the UBC faculty of medicine.

By systematically modifying the compounds at the molecular level, the researchers identified several promising candidates that effectively shut down the receptor. In animal studies, several compounds slowed prostate cancer growth more effectively than a commonly used prostate cancer treatment.

“What surprised us was how effectively these molecules could attach to a protein that doesn’t have a fixed structure,” said Dr Raymond Andersen, professor in UBC’s department of chemistry. “We were able to shut down the androgen receptor even in situations where current prostate cancer drugs stop working.”

The researchers now aim to advance the most promising candidates toward clinical trials, with the goal of developing prostate cancer drugs that can be used earlier in treatment and with fewer side-effects. Because disordered proteins are involved in many diseases, they say the approach could have a much broader impact.

“If the approach continues to prove successful, it could dramatically expand the number of proteins that scientists can target with medicines – turning what was once considered a dead end into a promising new frontier for drug discovery,” said Dr Sadar.

Source: University of British Columbia