Category: Gastrointestinal

Categories : GastrointestinalTags : Leave a comment

Unsafe Food Continues to Be a Global Health Hazard

On By ModernMedia
Escherichia coli. Photo by CDC on Unsplash

If it isn’t safe, it isn’t food – that message sits at the heart of a major new global effort by the World Health Organization (WHO).

University of Waterloo public health researcher Dr. Shannon Majowicz contributed research to the new WHO estimates, which cover the global burden of foodborne disease between 2000 and 2021. 

The estimates, which were released in mid-June alongside peer‑reviewed publications and webinars presenting key findings, represent the most comprehensive updates to date, bringing together global data on the illnesses, deaths and long-term health impacts such as paralysis, cancer and kidney disease associated with unsafe food. 

Foodborne diseases, which are largely preventable, remain a significant public health concern around the world, affecting hundreds of millions of people each year.

By standardising methods and bringing together data from across countries and regions, the new WHO estimates aim to provide governments, public health agencies and researchers with a clearer picture of where risks lie and how they can be reduced.

Waterloo expertise contributing to global effort 

Majowicz and collaborators updated 22 of the 42 WHO estimates, focusing on the global, regional and national burden of both diarrheal and invasive enteric pathogens, which contribute to serious illness, long-term complications such as kidney disease, paralysis, septicaemia, central nervous system infection, as well as death.

“Our aim was to better understand the burden of foodborne illness,” Majowicz says. “How many people are affected? How many develop severe consequences? How many die?”

This research highlights an important reality: Despite general declines over time, diarrhoeal and invasive enteric pathogens transmitted by contaminated food continue to be a substantial cause of illness and death globally.

In the study of diarrhoeal pathogens, Majowicz and colleagues found that in 2021, 14 diarrhoeal pathogens caused 666 million illnesses, with 265 000 deaths, due to contaminated food. The African continent bore the highest disease burden. In the invasive pathogen study, the transmission of eight pathogens by food caused 24 million illnesses, with 106 000 deaths, mostly in Africa and southeast Asia.  

Uneven global health challenge

Moreover, the studies, which are published in the Lancet Global Health (one on foodborne diarrhoeal and the other on foodborne non-diarrhoeal enteric disease hazards), reveal that foodborne disease remains an uneven global health challenge, with unsafe food disproportionately affecting children, populations in lower-income regions and communities with limited access to clean water, sanitation and strong food systems.

For example, children under five make up 9% of the population studied but bear 30% of the disease burden.

The updated estimates provide governments with the evidence they need to justify investing in food safety and foodborne disease prevention measures, Majowicz says. 

“By quantifying illness, death and long-term health impacts, these estimates give governments the data they need to invest in food safety systems, strengthen hygiene and infection prevention measures, improve surveillance and data collection and target interventions where they are needed most. 

“Without it, it can be difficult for policymakers to prioritize food safety alongside other urgent health issues.”

Source: University of Waterloo

Categories : GastrointestinalTags :

Can a Faecal Microbe Transplant Improve Chronic Insomnia?

On By ModernMedia
Photo by Andrea Piacquadio: https://www.pexels.com/photo/young-man-in-sleepwear-suffering-from-headache-in-morning-3771115/

In a randomised clinical trial published in the Journal of Internal Medicine, ingesting capsules containing faecal microbes from healthy donors helped treat symptoms of insomnia.

One month after treatment, participants receiving faecal microbiota capsules showed significantly higher sleep efficiency and reduced wake after sleep onset, as measured by overnight polysomnography. Patient questionnaires also showed that sleep quality scores improved from 2 to 6 months in the intervention group compared with the placebo group.

“Our findings provide clinical evidence that targeting the gut microbiota may offer a promising new therapeutic strategy for chronic insomnia disorder,” said co–corresponding author Yanping Bao, PhD, of Peking University, in Beijing. “This work also strengthens our understanding of the gut–brain axis as an important regulator of human sleep.”

Source: Wiley

Categories : Diet and Nutrition GastrointestinalTags :

Sweeteners Shown to Slow Growth of Important Gut Bacteria in Lab Tests

On By ModernMedia
Photo by Towfiqu barbhuiya

Cambridge researchers have shown how commonly-used sweeteners slow the growth of certain gut bacteria. Isosteviol – a compound derived from stevia (a common sweetener) – when combined with the anti-depressant duloxetine significantly impaired two important gut bacteria linked to regulating blood sugar and gut health and may affect the body’s immune responses.

Sweeteners are often marketed as metabolically neutral, but our study challenges this idea

Sonja Blasche

The scientists say more research is needed to understand the real-world health impacts of this laboratory study, one of the first to assess the direct impact of sweeteners on gut bacteria, particularly when they are combined with other substances.

Sweeteners are widely used in a range of food and drinks, including soft drinks, sweets, desserts, snacks and cereals. While marketed as healthier alternatives to sugar, there is increasing evidence of links to diseases such as type 2 diabetes, obesity and cancer.

Despite their pervasive use, there have been very few studies that look at the direct interactions between sweeteners and gut bacteria – the vast community of microorganisms that live in the digestive tract and play a crucial role in keeping our bodies healthy. 

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.

In research published in Molecular Systems Biology, Dr Blasche and colleagues looked at how artificial and low‑calorie sweeteners affect the bacteria living in our gut, and how these effects change when sweeteners are consumed together with other common substances such as caffeine, flavourings or medicines.

The researchers grew each of 25 gut bacterial species – including beneficial, neutral, and potentially harmful bacteria – in the lab. They then exposed each culture individually to 39 common, commercially-used sweeteners, some of which are artificial, others natural, and measured how well the bacteria multiplied.

Around three‑quarters of the sweeteners changed how at least one bacterial species grew. Some sweeteners slowed down or stopped the growth of certain bacteria linked to a healthy gut.

The researchers then tested each sweetener in combination with common compounds such as caffeine, vanillin (vanilla extract), advantame (an artificial sweetener) and eight commonly-used drugs to assess whether this had any impact on the gut bacteria. They found over 100 interactions where sweeteners acted differently when combined with other substances. In 34 cases, combinations made the effects stronger, while in 68 cases the effects were weaker.

Most striking was the combination of isosteviol (a compound derived from stevia, a sweetener widely used in the food and beverage industry) and the antidepressant duloxetine. This combination strongly suppressed Roseburia intestinalis and Parabacteroides merdae, two gut bacteria that play important roles in maintaining a healthy digestive system. In the US in 2023, over 4.2 million patients were prescribed duloxetine.

As no gut bacterium exists alone, but rather as part of a ‘community’ within the gut, the researchers created a synthetic community containing all 25 bacteria. After allowing it to grow over time, they tested the community against a variety of sweetener and drug combinations, looking at which species increased or decreased and whether the overall diversity changed.

By mimicking in this simplified way what might happen in the human gut, they showed that the combination of isosteviol and duloxetine reduced microbial diversity. A diverse microbiome is considered important for good gut health. The sweetener-drug combination also altered which bacterial species thrived or declined.

Further analysis showed that the effect of the isosteviol-duloxetine combination on the community increased toxicity towards certain host cells and interfered with other cells that play a role in the body’s inflammation and immune responses. 

Dr Blasche said: “Sweeteners are often marketed as metabolically neutral, but our study challenges this idea. We found that they can directly affect gut bacteria, particularly when mixed with other compounds such as medication and food additives. These common combinations could have unintended effects on our gut microbiome.”

The researchers stress that, as their experiments were carried out in the lab, not tested in humans, more research needs to be done before it is possible to conclude that there will be direct health effects in people. 

Professor Patil, the study’s senior author, added: “Our study suggests that artificial sweeteners don’t just pass through the body passively — they can interact with gut microbes, and these effects can be amplified or altered by other substances like medications. These findings can help guide new studies towards understanding how sweeteners might influence health in unexpected ways.”

The research was funded by the European Union’s Horizon 2020 programme and the UK Medical Research Council.

Reference

Blasche, S. et al. Common xenobiotics modulate gut microbial responses to low‑calorie sweeteners in vitro. MSB; 25 Jun 2026; DOI: 10.1038/s44320-026-00225-6

Republished from Cambridge University under a Creative Commons licence.

Read the original article.

Categories : GastrointestinalTags :

Researchers Use Friendly Viruses to Tackle Inflammatory Bowel Disease

On By ModernMedia

A targeted approach using bacteriophages to disarm harmful microbes without disrupting the broader gut ecosystem

Credit: CC0

A research team at McMaster University has developed a targeted approach to treating inflammatory bowel disease (IBD) using bacteriophages, viruses that infect specific bacteria, to disarm harmful microbes without disrupting the broader gut ecosystem.

The study, published in Science Translational Medicine and featured on the cover of the journal, brings together researchers from the Faculty of Engineering and the Faculty of Health Sciences, combining expertise in microbiome science and targeted antimicrobials to tackle a complex challenge in gut health.

Although current treatments for IBD can be effective, they can fail long-term or require escalating doses, increasing the risk of serious side effects.

IBD is shaped by a combination of genetics, immune responses and the gut microbiome. The research team focused on a group of bacteria known as adherent-invasive Escherichia coli (AIEC), which have been linked to inflammation in some people with Crohn’s disease. These bacteria can be difficult to identify and selectively target, making them an important test case for more precise microbiome-based therapies.

“One challenge is that AIEC are defined by what they do, not simply by how they appear in a microbiome analysis,” says Elena Verdu, professor in the Department of Medicine, director of the Farncombe Family Digestive Health Research Institute, and an executive member of NexusHealth.

“To identify them, we need to test their behaviour, such as their ability to adhere to and invade intestinal cells and persist in immune cells.”

Working with E. coli strains isolated from patients with Crohn’s disease, the team used controlled experimental models to isolate how AIEC contribute to inflammation and explore ways to neutralise their harmful behaviour without damaging beneficial bacteria.

To target AIEC without collateral damage, the team turned to bacteriophages, or phages, which are naturally occurring viruses that infect bacteria with remarkable precision.

“Phages work like a lock-and-key system – each phage targets only certain bacteria. That precision gives us a way to intervene without wiping out the entire microbiome,” explains Zeinab Hosseinidoust, associate professor in the Department of Chemical Engineering and the School of Biomedical Engineering and a member of the Michael G. DeGroote Institute for Infectious Disease Research (IIDR).

The team identified and characterised phages that selectively target AIEC strains isolated from patients with IBD and found that this approach significantly reduced gut inflammation.

The phages did not eliminate the bacteria entirely. Instead, they altered their behaviour by supressing a molecular “grappling hook” that helps AIEC attach to the gut lining and trigger immune responses. When that virulence mechanism was turned off, inflammation subsided.

“The bacteria were still there, but they lost the traits that drive inflammation,” says Hosseinidoust.

“We like to think of it as knocking out a few teeth. The bacteria can’t do as much damage anymore.”

The researchers also found that phage therapy enhanced the effectiveness of a commonly used steroid treatment for IBD. When combined with the phage, a lower-than-standard dose produced benefits comparable to higher doses of the drug alone.

While phages have previously been shown to increase the effectiveness of antibiotics, this is the first time a positive collaboration between phage and a non-antibiotic drug has been reported.

The findings point to a precision-medicine approach for IBD. The bacterial function targeted by the phage can be measured in stool samples and was found to be higher in a subset of patients with Crohn’s disease, suggesting a potential way to identify those who could benefit most from this therapy.

“If we can identify which patients carry the harmful bacterial function, we could, in the future, intervene with a targeted therapy designed specifically to turn down that activity,” says Verdu.

“This is what personalised medicine should look like: matching the right biological tool to the right patient,” says Hosseinidoust.

Next steps for the team include evaluating broader collections of bacterial strains from IBD patients and developing combinations of phages – work that brings the approach closer to human trials.

By Andrea Lawson

Source: McMaster University

Categories : GastrointestinalTags :

Analysis Reveals Path to More Effective Probiotic Supplements

On By ModernMedia
Photo by Harrison Cohen on Unsplash

Commonly available probiotic supplements contain an assortment of microbes sold for specific health purposes despite limited understanding of the microbes’ connections to their marketed use, new University of Virginia School of Medicine research reveals. But the scientists have assembled sophisticated computer models that could lead to more effective products to shape our microbiomes to improve health.

UVA researchers led by Jason Papin, PhD, analysed more than 350 over-the-counter probiotics sold at the three largest pharmacy chains in the United States – CVS, Walgreens and Walmart. Those 352 products were found to contain, collectively, only 36 unique species of bacteria. The most common species were forms of Lactobacillus, a type of bacteria commonly found in yogurt. 

More than half the products contained only one probiotic species. The products with the most unique species topped out at 17. Some brands maintained a consistent number of bacterial strains across products, while others did not.

Based on their analysis, the scientists concluded that there was no real consistency in the combination of species used to support gut health, vaginal health or other health claims. 

“It is truly fascinating to discover that these probiotic bacteria hold a unique, specialized niche among the trillions of microbes in and on the human body,” said Glynis Kolling, PhD, a research faculty member in UVA’s Department of Biomedical Engineering who works closely with Papin. “By combining our advanced methods, we have the potential to vastly expand the pool of beneficial bacteria and pave the way for targeted solutions to support human health.”

Targeting the Microbiome

We have at least as many microorganisms living on and inside us than we have cells in our bodies. Scientists have increasingly come to appreciate the role these microorganisms – collectively known as the microbiome – play in maintaining our health. We can get beneficial bacteria from our diets, such as from yogurt and fermented foods, but there has also been an explosion in “probiotic” products over the last two decades.

So far, the federal Food and Drug Administration has approved only two microbial products for therapeutic purposes, and both are used to treat recurrent C. difficile infections in the colon. Supplements, however, are not regulated as strictly as drugs in the United States, and there is limited understanding of connections between bacteria and marketed use for many probiotic products, the UVA researchers found.

To improve the effectiveness of probiotic products, Papin and his team have developed HaPaPro, a collection of more than 1000 computer models of bacterial metabolism. They used these models to see if they could identify probiotics with the potential to improve women’s vaginal health.

The vaginal microbiome is a natural ecosystem of bacteria, fungi and other microbes that help support health. Bacterial vaginosis occurs when this natural ecosystem is disrupted, leading to pregnancy complications, pelvic inflammatory disease, higher risk of sexually transmitted disease and general discomfort. The researchers were able to use their models to identify microbes that have the potential to help prevent bacterial vaginosis

The successful results, Papin says, demonstrates HaPaPro’s potential for identifying ways to manipulate the microbiome will have concrete benefits. Such insights, he hopes, will lead to better probiotic products that deliver on their promises.

“It is remarkable how much microbes play a role in human health and well-being,” Papin said. “I love seeing how computational models of these complex biological systems are leading to new ideas for therapies and helping us understand such fundamental biological processes.”

Findings Published

The researchers have published their findings in the scientific journal Nature Microbiology. The research team consisted of Emma M. Glass, Kolling and Papin. The scientists have no financial interest in the probiotic industry, but Papin disclosed he has a stake in Cerillo, the manufacturer of instrumentation used in some of the analyses.

Source: University of Virginia

Categories : GastrointestinalTags :

Decades-old Puzzle Solved as Scientists Uncover Cause of IBD

On By ModernMedia

Scientists have identified the missing link between a long-known genetic signal in inflammatory bowel disease and a damaging immune response that switches off the body’s natural control of inflammation – opening the door to faster diagnosis and targeted treatment.

Interleukin-10.

Researchers at the Nuffield Department of Medicine, University of Oxford, together with Newcastle University’s Translational and Clinical Research Institute and the Department of Immunology at Cambridge University Hospitals NHS Foundation Trust, have identified an important driver of inflammatory bowel disease (IBD). This discovery reshapes understanding of IBD and opens the way to targeted approaches to diagnosis and treatment in a subset of patients. The findings suggest that inflammatory bowel disease is not a single condition, but a group of biologically distinct diseases driven by different underlying mechanisms.

In a study published in the New England Journal of Medicine, researchers analysed over 4900 patients with IBD and made two major discoveries: first, that a substantial subset of patients show autoimmune responses to one of the guardians of the immune system, interleukin-10 (IL-10), which leads to uncontrolled inflammation; and second, that this damaging immune response is the mechanism for one of the strongest known genetic risk factors for IBD.

Antibodies that block interleukin-10 (IL-10), a cell-to-cell messenger that normally acts as one of the body’s key controls on inflammation, effectively remove the immune system’s natural ‘brake’ on inflammation, allowing inflammatory responses to continue unchecked.

IBD, which includes Crohn’s disease and ulcerative colitis, affects around 500 000 people in the UK and millions worldwide. It is a lifelong condition that commonly begins in adolescence or early adulthood and can require repeated hospital treatment, long-term immunosuppressive medication and, in some cases, surgery. Despite advances in treatment, many patients cycle through multiple therapies without achieving lasting disease control – impacting their lives and costing the health care system millions.

The researchers found high levels of anti-IL10 neutralising autoantibodies in the blood of around 3.5% of IBD patients, both Crohn’s disease and ulcerative colitis, but not in healthy individuals. This could equate to 15 000-20 000 people with IBD in the UK carrying these autoantibodies.

The researchers also found that the presence of these antibodies was strongly linked to carriage of a particular genetic variant known as HLA-DRB1*01:03.

The link between HLA-DRB1*01:03 and a severe form of inflammatory bowel disease was first identified by Oxford researchers 30 years ago. The new findings show that people carrying this variant are far more likely to develop antibodies that block IL-10, helping explain how the gene contributes to disease.

The Oxford IL-10 Research GroupProfessor Holm Uhlig, a Paediatric Gastroenterologist and Director of the Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, and a senior author of the study, said: ‘We’ve suspected an important role of interleukin 10 in patients with inflammatory bowel disease for decades. The study now provides clear evidence and contributes the missing link between a well-known genetic variant that had been linked to severe inflammatory bowel disease in the past and the very recently discovered autoimmunity to interleukin 10. 

‘Understanding what drives the inflammation, provides a clear explanation for disease in this group of people and opens the door to new treatments that target the autoantibodies themselves or cells that produce those autoantibodies.’

The paper, ‘IL-10 Autoantibodies and HLA-DRB101:03 in Inflammatory Bowel Disease’, is published in the New England Journal of Medicine.

Source: University of Oxford

Categories : Gastrointestinal Mental HealthTags :

Can Probiotics Help Treat Depression?

On By ModernMedia
Gut Microbiome. Credit Darryl Leja National Human Genome Research Institute National Institutes Of Health

In a pilot clinical trial published in the Journal of the American Geriatrics Society that included older adults with depression receiving standard care, adding probiotic therapy produced modest but meaningful reductions in depressive and anxiety symptoms compared with adding a placebo. However, both groups demonstrated substantial overall improvements during follow-up.

For the trial, 58 participants in India aged ≥ 60 years with moderate depression were randomised 1:1 to receive daily probiotics or a placebo for 12 weeks, alongside standard antidepressant care. They were followed up for another 12 weeks.

Based on validated psychological scores, biomarker (serum brain-derived neurotropic factor level), and faecal microbiota profiling, investigators found that probiotics helped improve patients’ symptoms but did not confer clear additional gains in quality of life compared with placebo.  The findings support probiotics as a safe, biologically plausible adjunct to standard care, but larger trials are needed.

“The results of our study are novel, and we are now planning a follow-up, larger-scale clinical trial due to the encouraging findings,” said co-corresponding author Dr. Saibal Das, MBBS, MD, DM, PhD, of the Indian Council of Medical Research – National Institute for Research in Bacterial Infections, Kolkata. “My vision is to develop affordable healthcare solutions and make them available to the larger population for meaningful public health impact,” added co–corresponding author Abhinaba Ghosh, MBBS, MSc, PhD, a physician-neuroscientist from Tata Medical Center, Kolkata.

Source: Wiley

Categories : Diet and Nutrition GastrointestinalTags :

Cutting Out Sucrose from the Diet May Disrupt Gut Microbiome

On By ModernMedia
Photo by Sharon Mccutcheon on Unsplash

Eliminating sugar from your diet may be more detrimental than previously thought, according to an animal study being presented Saturday at ENDO 2026, the Endocrine Society’s annual meeting in Chicago, Ill.

“Completely removing sucrose from a low-fat diet may unexpectedly disrupt gut health and promote inflammation and metabolic dysfunction, highlighting that balanced nutrition is more important than simply eliminating sugar,” said Rasheed Ahmad, PhD, principal scientist and head of the Immunology & Microbiology Department at the Dasman Diabetes Institute, in Kuwait City, Kuwait. The institute was founded by Kuwait Foundation for the Advancement of Sciences. Researchers investigated the effects of a sucrose-free low-fat diet compared to a sucrose-containing low-fat control diet in two groups of mice for 16 weeks. 

They evaluated glucose tolerance, insulin sensitivity, circulating metabolic hormones, the gut microbiome and inflammation in the colon and liver.

Mice fed the sucrose-free diet developed impaired glucose control, insulin resistance, gut microbial imbalance, intestinal inflammation and fatty liver changes, despite having no significant differences in body weight compared with control mice. 

“The findings suggest that complete removal of sucrose from a low-fat diet may negatively affect gut microbiota and metabolic health,” Ahmad said. “The study highlights the importance of maintaining balanced dietary carbohydrates to support gut and immune homeostasis.” 

Until now, the consequences of restrictive diets that eliminate sugar from a low-fat diet were unknown.

“This research may influence future dietary recommendations by emphasizing the importance of maintaining a healthy gut microbiome rather than focusing only on sugar restriction,” Ahmad said. “In the long term, these findings could help improve strategies for preventing and managing metabolic disorders, fatty liver disease and chronic inflammatory conditions.”

“Studies such as this reflect our institute’s commitment to advancing evidence-based scientific discoveries that improve public health outcomes and deepen our understanding of metabolic disease,” said Faisal Hamed Al-Refaei, MD, Acting Director General of Dasman Diabetes Institute.

Source: Endocrine Society

Categories : GastrointestinalTags :

Why Midnight Eating Can Be a Gut Punch

On By ModernMedia

Study finds that intestinal circadian clocks become misaligned by off-schedule eating, causing gastrointestinal issues

A microscopic image shows enteric neurons (orange) and macrophages (green) in the muscularis externa of a mouse small intestine. Muscularis macrophages were among the intestinal cell types that glowed green when a key circadian clock gene called Per2 was active during UT Southwestern investigators’ research.

Eating when the body is normally asleep appears to desynchronise the circadian clocks of different cell types in the intestines, a UT Southwestern Medical Center study suggests. The findings, published in PNAS, could help explain why shift work, jet lag, and other environmental stressors that affect circadian rhythms are associated with irritable bowel syndrome, inflammatory bowel disease, constipation, and other gastrointestinal disorders.

“Understanding how intestinal circadian clocks become misaligned may ultimately guide strategies involving meal timing, circadian-based therapies, or dietary interventions to improve gastrointestinal and metabolic health,” said Yuuki Obata, PhD, Assistant Professor of Immunology and Neuroscience at UT Southwestern. Dr Obata co-led the study with Shin Yamazaki, PhD, Professor of Neuroscience.

Research in the 1990s and 2000s showed that a region of the brain known as the suprachiasmatic nucleus (SCN) acts as a master timekeeper for the body, setting various cellular processes to occur rhythmically on a 24-hour period based on cycles of light and darkness. However, in 2000, Dr Yamazaki and his colleagues showed that cells throughout the body have their own autonomous circadian clocks that are influenced both by signals from the SCN and environmental cues.

In line with this idea, research has shown that the intestines have their own rhythms that can be influenced by a variety of factors, such as timing of meals. These findings were made using whole intestinal tissue, Dr Obata explained, but the intestines contain a variety of cell types – including muscle, nerve, and immune cells. It’s been unclear whether each of these populations has its own circadian clock and if they run on the same schedule.

To find out, Drs Obata and Yamazaki monitored novel mice with set 12-hour cycles of light and dark. They were engineered by Joseph Takahashi, PhD, Chair and Professor of Neuroscience at UT Southwestern, and his colleagues in the Takahashi Lab. Five intestinal cell types – enteric neurons, enteric glial cells, interstitial cells of Cajal (ICCs), smooth muscle cells, and muscularis macrophages – glowed green when a key circadian clock gene called Per2 was active. Although food was available at all times, the mice ate about 80% of their meals at night due to their nocturnal nature.

After about a week in this environment, the researchers observed intestinal cells glowing green at approximately the same times, suggesting the different cell populations had their own autonomous circadian clocks that cycled in sync. But when the researchers made food available only for four hours in the daytime – forcing the mice to eat at abnormal times – Per2 activity shifted to match this new rhythm in every cell population except for the ICCs. These cells resisted changes to their circadian clock, staying out of sync with the other cell types for weeks.

Such asynchrony may also occur in people who eat outside the body’s usual circadian rhythms, such as night shift workers or those who fly to different time zones. Because ICCs play a key role in intestinal motility, their resistance to adapt to a changed circadian clock could affect digestive and metabolic function.

Finding a way to synchronise the different intestinal cell populations through diet, probiotics, or drugs could eventually help ease the gastrointestinal problems associated with altered circadian timing, the researchers said.

Source: UT Southwestern Medical Center

Categories : GastrointestinalTags :

Promising Molecule for Coeliac Targets Gluten in the Stomach

On By ModernMedia
Photo by Mariana Kurnyk

A research project led by the Institute for Research in Nutrition and Food Safety (INSA) and the Faculty of Pharmacy and Food Sciences at the University of Barcelona, together with the Molecular Biology Institute of Barcelona (IBMB) of the CSIC (which stands for Consejo Superior de Investigaciones Científicas), has successfully designed and tested a gluten-degrading molecule that is a promising ally in the management of coeliac disease, an autoimmune disease whose symptoms are triggered by the consumption of gluten and other prolamins found in cereals. At present, there is a complete lack of treatment options beyond a diet free from gluten, which is difficult to maintain in Western societies where diets rely heavily on wheat products.

The major breakthrough is that the molecule is effective at very low concentrations and at a pH of 2 (the pH of the stomach) a condition that none of the molecules currently available or under development had previously achieved with efficiency. Although some of them are marketed as nutritional supplements, they are not an effective alternative to gluten-free diets.

The study has been published in the journal EMBO Molecular Medicine ahead of the International Day of Coeliac Disease on 16 May and is led by researchers Francisco J. Pérez-Cano (INSA-UB), and F. Xavier Gomis-Rüth (IBMB-CSIC). The co-first authors are Marina Girbal-González and Arturo Rodríguez-Banqueri (INSA-UB and IBMB-CSIC, respectively). Teams from the Institute for Food Science Research (CSIC-UAM), the University of Salzburg (Austria) and the Technical University of Munich (Germany) have also participated.

Counteracting the ‘trigger’ of coeliac disease

The trigger for coeliac disease are the prolamins, proteins found in most common cereals in our diet, such as wheat gluten. When these are digested in the stomach, they break down into smaller fragments (peptides). Some of these can be toxic, such as the gluten immunogenic peptides (GIPs), which can withstand the stomach’s gastric acids and reach the small intestine. Among these, one of the most immunogenic is the the ‘33-mer’, a fragment of the α-gliadin in wheat gluten that is highly immunogenic.

This poses a problem for people with coeliac disease, because once in the small intestine, the 33-mer and other GIPs bind particularly easily to a receptor of the immune system (the human leukocyte antigen, or HLA), triggering the inflammatory autoimmune response that causes the characteristic symptoms of the disease.

The results demonstrate that celiacase, a molecule stable in the stomach environment, could be an adjunctive therapeutic candidate to support a gluten-free diet.

Four years ago, the Proteolysis Group at IBMB-CSIC, led by F. Xavier Gomis-Rüth, described in an article in Nature Communications that nephrosin – a molecule found naturally in the digestive juices of the carnivorous plant Nepenthes ventrata – was capable of cleaving GIPs, building on results from the group of David Schriemer from the University of Alberta in Canada. In collaboration with the Autoimmunity, Immunonutrition and Tolerance Group at the UB’s Faculty of Pharmacy and Food Sciences, led by Professor Francisco José Pérez-Cano, they demonstrated that nephrosin can degrade the 33-mer peptide and other GIPs before they reach the intestine, thereby potentially preventing this autoimmune inflammatory response.

Designed using molecular engineering

In this study, the team has designed and tested a molecule based on nephrosin. Named celiacase, this new molecule exhibits its maximum activity at the gastric pH of the stomach, where, in synergy with the pepsin in our digestive system, it breaks down the GIPs in cereals and the gliadin in wheat before they pass into the duodenum.

“There are other proteases, generically termed glutenases, which break down gluten, but they are not fully active at pH 2 – the pH of the stomach – but rather at pH 7 – the pH of the duodenum – when the bolus has already left the stomach,” explains Gomis-Rüth. “Therefore, it is necessary to increase the doses to levels that make them unviable for therapeutic use.”

The team has tested the molecule in vivo using a mouse model developed by the University of Chicago, which is currently the model that most accurately replicates coeliac disease. The results show that celiacase is effective at very low doses, being able to mitigate the symptoms of the disease in gluten-fed mice, even at high gluten intake levels. “Intestinal atrophy, inflammation, the antibody response and dysbiosis – that is, the alteration in the composition of the microbiota – were reduced,” says Pérez-Cano. “Furthermore, immunoregulatory markers were restored to normal levels, as were microbial metabolic pathways.”

Another advantage of celiacase is that it is no longer active once it reaches the duodenum. “Once it has accomplished its function, there is no need for it to remain active, so that it does not interfere with other proteins in the body,” adds Gomis-Rüth.

The molecule and its potential applications have been patented, and the team is taking the first steps towards setting up a spin-off company and taking the development to more advanced stages.

This study has been partially funded by programmes run by the Ministry of Science and Innovation, the Government of Catalonia’s Agency for Management of University and Grants (AGAUR) AGAUR, the Catalan Coeliac Association, and the CSIC’s Conexión Trigo network.

Video

Source: University of Barcelona