Gastroenterology News

According to McMaster University’s Waliul Khan, long-term usage of the food colour Allura Red may be a risk factor for IBDs, Crohn’s disease, and ulcerative colitis. According to research using experimental animal models of IBD, continuous exposure to Allura Red AC is damaging to gut health and promotes inflammation.

The dye inhibits gut barrier function and increases serotonin production, an intestinal hormone/neurotransmitter that alters the makeup of the gut microbiota and increases the risk of colitis. According to Khan, Allura Red, also known as FD&C Red 40 and Food Red 17, is a common component in candy, soda, dairy products, and some cereals.

Foods are coloured and given texture with the dye, frequently to draw in children.

Over the past few decades, the usage of artificial food colours like Allura Red has grown considerably, but there hasn’t been much prior research on how these colours affect gut health. In Nature Communications, Khan and his team revealed the results of their research. The first author is Yun Han (Eric) Kwon, a recent PhD graduate working in Khan’s lab.

“This study demonstrates significant harmful effects of Allura Red on gut health and identifies gut serotonin as a critical factor mediating these effects. These findings have important implications in the prevention and management of gut inflammation,” said Khan, the study’s senior author, a professor of the Department of Pathology and Molecular Medicine and a principal investigator of Farncombe Family Digestive Health Research Institute.

“What we have found is striking and alarming, as this common synthetic food dye is a possible dietary trigger for IBDs. This research is a significant advance in alerting the public on the potential harms of food dyes that we consume daily,” he said.

“The literature suggests that the consumption of Allura Red also affects certain allergies, immune disorders and behavioural problems in children, such as attention deficit hyperactivity disorder.”

Khan said that IBDs are serious chronic inflammatory conditions of the human bowel that affect millions of people worldwide. While their exact causes are still not fully understood, studies have shown that dysregulated immune responses, genetic factors, gut microbiota imbalances, and environmental factors can trigger these conditions.

Significant progress has been made in identifying susceptibility genes and understanding the involvement of the immune system and host microbiota in the pathogenesis of IBDs in recent years. However, he claims that similar breakthroughs in pinpointing environmental risk factors have lagged.

Environmental factors for IBDs, according to Khan, include the usual Western diet, which contains processed fats, red and processed meats, sweets, and a lack of fibre. He went on to say that the Western diet and processed foods contain a lot of different chemicals and colours.

He went on to say that the findings reveals a relationship between a frequently used food colour and IBDs and that greater research into food dyes and IBDs is needed at the experimental, epidemiological, and clinical levels.

Stroke is a major cause of dementia, significant long-term damage, and death. According to the American Heart Association, stroke patients are more likely to develop depression, which has a negative impact on functional and cognitive recovery.

The Texas A&M researchers looked at whether transplanting intestinal epithelial stem cells (IESCs) from healthy donors may restore the intestinal barrier after stroke and enhance outcomes. According to the findings of their preclinical investigation, published in the journal Brain, Behavior, and Immunity, IESC transplantation reduced stroke-induced mortality, reduced the amount of dead tissue and gut leakiness, and averted stroke-induced cognitive impairment.

The only recombinant tissue plasminogen activator approved by the FDA for stroke therapy has a limited track record and must be taken shortly after the beginning of the stroke. Texas A&M University School of Medicine researchers are spearheading research into the association between stroke-induced intestinal permeability, or leakiness, and cognitive impairment, with the objective of improving stroke outcomes.

According to recent research, two-thirds of stroke patients will develop cognitive impairment, and one-third of all stroke patients will develop dementia, so there is a critical need for more effective stroke therapies that preserve cognitive function after acute stroke and remain protective in the weeks following.

Although most stroke therapy research is focused on the brain, the gut responds to stroke quickly and with alterations that may predict many of the inflammatory processes associated with stroke-induced illness. These alterations in the gut, such as increased permeability, are likely to result in the transfer of products generated in the gut into the bloodstream. Many of these products are hazardous, posing a risk of increasing inflammation and exacerbating stroke-induced brain damage.

IESCs heal the gut and decrease permeability, according to evidence from a range of research. These healing pathways may be crucial in retaining cognitive function after a stroke.

“It is clear that the gut-brain axis is involved in injury following stroke,” said Farida Sohrabji, PhD, Regents Professor, department head for Neuroscience and Experimental Therapeutics and senior author of the study. “Factoring in the effects of gut health on the brain following stroke may allow us to more effectively advance stroke therapies.”

In a preclinical model, Sohrabji and her colleagues implanted primary IESCs from healthy donors following stroke.

IESCs derived from young donors restored gut architecture and lowered gut permeability, lowering blood levels of proteins and other chemicals harmful to brain cells. In the weeks following the stroke, IESC transplantation also reduced depressive-like behaviours and cognitive impairment. IESC transplantation from older donors did not enhance stroke outcomes, demonstrating that donor age influences transplant success.

This research, which is still in the preclinical stage, emphasises the necessity of early treatment intervention after stroke and will influence future directions of the work. “Future trials will look towards refining the protocol’s dose and timing,” Sohrabji added. “A comprehensive study of ageing stem cells might also be useful in explaining why older people have more severe strokes.”

Sohrabji, a neurologist who has made major contributions to the literature on stroke causation, revealed that Kathiresh Kumar Mani, PhD, an associate research scientist in her lab, directed this preclinical work. The American Heart Association provided a postdoctoral grant to Mani, who is versed in gut biology, to assist this investigation.

Their combined knowledge has enabled them to take stroke treatment research into new area, with promising outcomes. They also won a large grant from the WoodNext Foundation, which is assisting them with their unique research.

“Ultimately, this research is expected to advance development of novel therapies that target and repair the intestinal epithelium to help mitigate stroke disability,” Sohrabji said, “but the premise–that gut stem cells might be therapeutically valuable outside of the gut–could be considered for a much greater variety of neurological diseases.”

Changes in gut function caused by weight gain are linked to an increase in the severity of asthma, according to research that will be presented at the Society for Endocrinology annual conference in Harrogate. Gaining weight, according to the study, is connected with higher levels of inflammation, indications of gut permeability, and less effective asthma control. These findings suggest not only to weight loss as a viable therapy option for individuals with severe asthma symptoms, but also to the stomach as an additional therapeutic target for improving asthma control in obese patients.

It has previously been proven that gaining weight modifies the nature of the bacteria in the gut, perhaps increasing gut permeability. A “leaky gut” can let deadly pathogens into the circulation, triggering inflammatory responses throughout the body. Obesity has been linked to an increase in the severity of chronic inflammatory disorders such as asthma. Although it is common, poorly treated asthma can have serious side effects such as tiredness, lung infections, and an increased chance of life-threatening asthma episodes. There has been no previous research on how increasing intestinal permeability may affect asthma management.

Cristina Parenti and colleagues at Nottingham Trent University studied the symptoms of 98 people with severe asthma, as well as the relationship between body weight and gut permeability. Patients with a lean-to-obese body mass index (BMI) reported their symptoms using the Asthma Control Questionnaire-6. Blood tests were used to measure asthma-related inflammatory markers and gut permeability markers (lipopolysaccharide binding protein (LPB) and calprotectin) (granzyme-A, IL-5, IL-6, CCL-4). LBP levels were significantly higher in individuals with poorly controlled asthma, and they increased with body weight. Rising LBP concentrations are associated with increased levels of inflammatory markers related to asthma.

Lead investigator, Cristina Parenti, commented, “We have found a significant link between gut permeability, being overweight and poor asthma control, particularly in people with obesity. This suggests that dietary interventions to improve gut barrier function may be an effective, alternative treatment target for asthma patients who are overweight or have obesity.”

The current study comprised just a limited number of people with severe, uncontrolled asthma. The researchers plan to engage additional participants in the study, look at the results in people with well-controlled asthma across a variety of BMIs, and see if focusing on the stomach can benefit people with asthma management.
“Our preliminary findings indicate that increased gut permeability is likely to be a factor in worsening asthma symptoms in obese patients, so it will be interesting to see if dietary interventions can improve symptoms for these patients,” Cristina Parenti concluded.

According to a recent mouse research, the bacteria that assist break down food actually instruct the stomach how to do their job better. According to the researchers, bacteria appear to be able to control which of the gut’s genes are activated, and this interaction may lead to a remodelling of the epithelial cells lining the gut to fit the diet. According to the researchers, bacteria appear to be able to control which of the gut’s genes are activated, and this interaction may lead to a remodelling of the epithelial cells lining the gut to fit the diet.

“The gut is a wonderful link between an animal and the world it lives in, and it receives information from both the nutrition and the bacteria it houses,” said John Rawls, Ph.D., director of the Duke Microbiome Center and professor of molecular genetics and microbiology at Duke. The findings were published in the open access journal Cellular and Molecular Gastroenterology and Hepatology on May 6. To begin parsing the instructions sent by microorganisms to gut cells, Duke researchers compared mice grown without gut microbes to those raised with a normal gut microbiome.

The researchers concentrated on the interaction between RNA transcription (DNA being transcribed to RNA) and the proteins that switch this copying process on or off in the small intestine, which is where most fat and other nutrients are absorbed. While both germ-free and normal mice were able to metabolise fatty acids in a high-fat diet, the researchers discovered that germ-free mice employed a whole distinct collection of genes to deal with the high-fat meal.

“We were shocked to see that the gene playbook used by the gut epithelium to respond to dietary fat differs depending on whether or not microorganisms are present,” Rawls said. The researchers also discovered that microorganisms can aid in fat absorption in the stomach.

“It’s a really consistent conclusion across numerous studies, from our lab and others, that microorganisms actually improve lipid absorption,” said Colin Lickwar, Ph.D., senior research associate in Rawls’ lab and the paper’s lead author. “And, to some extent, this influences systemic processes such as weight growth.” The germ-free mice showed an increase in the activation of genes involved in fatty acid oxidation, which is the actual burning of fatty acids to supply fuel for the gut’s cells.

“We usually conceive of the gut as merely performing its job, absorbing food nutrients through the epithelium to share with the rest of the body,” Rawls added.

“What we believe is happening in germ-free mice is that the stomach consumes more fat than it would if the microorganisms were there.” This might be due to changes in the makeup of the gut’s epithelial cells.
“A number of recent articles have shown that there is a significant ability to affect the broader architecture of the gut as well as particular gene programmes,” Lickwar added. “The gut has an amazing amount of flexibility.” We don’t fully understand it, but this article sheds some light on it.”

The researchers concentrated their efforts on HNF4-Alpha, a transcription factor known to control genes involved in lipid metabolism and genes that respond to microorganisms.

“We thought that it might represent an interface or a crossroads between interpreting information that comes from either microbial sources or from dietary fat,” Lickwar said.

“It’s certainly complicated, but we do appear to identify that HNF4-Alpha is important in simultaneously integrating multiple signals within the intestine,” Lickwar said.”For every way that germ-free animals seem unusual, that teaches us something about the large impact of the microbiome on what we consider to be ‘normal’ animal biology,” Rawls said.

Probiotic bacteria function better to lower gut inflammation when they are equipped with the greatest equipment, similar to expert firefighters travelling into the wilderness to fight an out-of-control fire. The research was published in the journal Science Advances. A recent study from the University of Wisconsin-Madison shows how much potential some gut-friendly bacteria have for enhancing therapies for inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis.

The research is led by Quanyin Hu, a biomedical engineer and professor at the University of Wisconsin-Madison School of Pharmacy. Previously developed technology encases helpful bacteria in a very thin protective shell, allowing them to survive an onslaught of stomach acids and competing germs long enough to establish and flourish in the stomachs of mice.
While technology makes orally delivered probiotics more effective, IBD is a complicated illness that generally includes more than just out-of-whack gut microbial ecosystems.

“IBD is a difficult condition that requires multiple approaches,” adds Hu. As a result, Hu and his colleagues developed customised nanoparticles to neutralise chemicals linked to IBD. They’ve also discovered out how to connect these nanoparticle “backpacks” to helpful bacteria after they’ve been coated with a protective covering. When combined with probiotics, these nanoparticle backpacks have the potential to greatly enhance – and simplify – IBD therapies.

While the underlying reasons of IBD are complicated and under investigation, one issue is the overproduction of chemicals known as reactive oxygen species. These molecules are necessary for many human bodily processes, but too many of them in the stomach can cause harmful inflammation along the intestinal lining. Here come the nanoparticle backpacks. The small particles are made up of sulphide and hyaluronic acid. The acid has a strong anti-inflammatory effect, while the sulphide directly targets reactive oxygen species.

Hu’s recent study, which was conducted in mice, found that probiotic bacteria Escherichia coli Nissle 1917 wrapped in a protective shell and furnished with nanoparticle backpacks are substantially better at treating IBD symptoms than their counterparts who did not have the extra gear. The researchers measured the impact of the therapies in two ways: by evaluating weight changes and colon length changes in mice with IBD who received and did not receive the therapy.
Weight loss and colon shrinkage are typical in mice with IBD, just as they are in people. Hu and his colleagues discovered that mice that received the entire therapy lost the least amount of weight and had significantly less colon shortening than mice who received partial or no treatment.

Current treatment choices vary depending on the stage and severity of the disease, according to Hu and his colleagues, who are looking for a more comprehensive treatment that might be beneficial at any stage.
“For me, that’s the most intriguing element of this research,” Hu adds. “We didn’t want to focus on a certain stage of IBD. We aimed to pick the most crucial aspects that help cure or treat the disease at any stage.”
Furthermore, the therapy is delivered orally, which may make it a more appealing option to other more invasive kinds of IBD treatment, such as partial or total colon removal.

While the results are promising, the therapies will not be evaluated in people for some time. Hu’s next goal is to see if the nanoparticle backpacks function well with different probiotic bacteria species and if the therapy has any unwanted side effects. Simplifying the procedure of producing and connecting the nano-backpacks will also be critical for clinically viable therapies.

Man is a sociable animal, as are other primates. Healthy social ties help people stay in good health, both emotionally and physically. According to a new study published in ‘Frontiers in Microbiology,’ the gut microbiome, which keeps the human gut in good shape, plays an important role in keeping our bodily systems intact. So, how does social interaction fit into the gut microbe’s complex and diversified nexus? Dr. Katerina Johnson assists us in our investigation.

Johnson is a research associate at the University of Oxford’s Departments of Experimental Psychology and Psychiatry. The researchers concentrated on a single social group of rhesus macaques (22 males and 16 females between the ages of six and twenty years) on the island of Cayo Santiago, off the eastern coast of Puerto Rico. Macaques were once found only in North Africa and Asia. However, in 1938, 409 rhesus macaques were relocated from India to Cayo Santiago.

On the 15.2-hectare island today, over 1,000 macaques are divided into several social groups. They are free to roam and forage, though their diet is supplemented daily with monkey chow. Every year, researchers conduct behavioural studies on the monkeys.

Between 2012 and 2013, the authors collected a total of 50 uncontaminated stool samples from this social group. As a measure of social connectedness, they used the time each monkey spent grooming or being groomed in 2012 and 2013, and his or her number of grooming partners.

Co-author Dr Karli Watson, from the Institute of Cognitive Science at the University of Colorado Boulder, explained: “Macaques are highly social animals and grooming is their main way of making and maintaining relationships, so grooming provides a good indicator of social interactions.”

“Engagement in social interactions was positively related to the abundance of certain gut microbes with beneficial immunological functions, and negatively related to the abundance of potentially pathogenic members of the microbiota,” said co-author Dr Philip Burnet, a professor from the Department of Psychiatry at the University of Oxford.

For example, genera more abundant in the most sociable monkeys included Faecalibacterium and Prevotella. Conversely, the genus Streptococcus, which in humans can cause diseases such as strep throat and, pneumonia, was most abundant in less sociable monkeys.

“It is particularly striking that we find a strong positive relationship between the abundance of the gut microbe Faecalibacterium and how sociable the animals are. Faecalibacterium is well known for its potent anti-inflammatory properties and is associated with good health,” said Johnson.

But what drives the relationship between social connectedness and gut microbiome composition? Distinguishing between cause and effect isn’t easy.

“The relationship between social behavior and microbial abundances may be the direct result of social transmission of microbes, for example through grooming. It could also be an indirect effect, as monkeys with fewer friends may be more stressed, which then affects the abundance of these microbes. As well as behavior influencing the microbiome, we also know it is a reciprocal relationship, whereby the microbiome can in turn affect the brain and behavior,” said Johnson.

In persons with inflammatory bowel disease, the intestine becomes inflamed, which can thicken the gut wall and result in a potentially deadly obstruction of the intestinal tube. This mystery condition known as “fibrosis” affects 20 to 50% of Crohn’s disease and ulcerative colitis patients throughout the course of their lives. “Aside from surgery to remove the blocked section of intestine, there are currently no approved treatments for this condition,” said Dr. Simon Hirota, PhD, Canada

Research Chair in Host-Microbe Interactions and Chronic Disease and member of the Snyder Institute for Chronic Diseases at the University of Calgary’s Cumming School of Medicine. Hirota’s recent study, which was published in the journal Cellular and Molecular Gastroenterology and Hepatology, sets the door for the development of a potentially viable fibrosis therapy. The study included researchers from the Albert Einstein College of Medicine in New York and the University of Calgary.

The researchers looked at the bacteria that dwell in the human gut, dubbed “the inner tube of life,” and create microbial metabolites, which are metabolic byproducts that prevent inflammation and gut wall thickening. These compounds, as well as the body’s natural receptors for detecting them, are less common in those suffering from inflammatory bowel disease.
Hirota observed that, while the gut must mend itself after an injury, the “over-exuberant” continuous healing seen in inflammatory bowel diseases causes changes to the gut wall that feed disease.
“We’re now suspecting that the fibroblast cells just under the lining may also play a role in perceiving and reacting to metabolites,” Hirota added.

The study focused on PXR, a chemical sensor or receptor in the gut that is important in aiding gut repair. They focused on the interaction between this receptor and a metabolite known as IPA.
The researchers employed cells from mice with the PXR receptor removed to identify the cells involved in the interaction between the host and the chemicals produced by gut bacteria. They employed human intestinal cells to confirm their findings in the animal model.
Medication designed to directly target these sensors, according to the study, may offer a novel strategy to treating inflammation-related intestinal blockage.

Co-author Dr Sridhar Mani, MD, and his research team produced synthetic compounds based on the structure of the IPA metabolite in the same way as natural IPA reduces inflammation.
“This novel research has resulted in a field-leading article that clearly implicates PXR as a crucial target for fibrosis,” adds Mani, an Albert Einstein College of Medicine professor. “We now seek to leverage microbial metabolite mimicry as a way to target PXR in order to avert this terrible IBD consequence.” Clinical studies would be the next stage in determining if synthetic compounds have a good effect on fibrosis and human gut remodelling. The “synthetic metabolite,” according to Hirota, should ideally be in a form that can be digested, passed through the stomach, and then released in the injured portions of the gut.

Gut microbes, according to a recent research, trigger specialised cells to cut off unnecessary connections in brain regions that control social behaviour. Pruning is necessary for healthy social behaviour to evolve.
The researchers also discovered that these’social’ neurons in zebrafish and mice are identical. This implies that the findings may be applicable across species and may open the way to therapies for a variety of neurodevelopmental diseases. “This is a significant step forward,” said Judith Eisen, a UO neurologist who co-led the study with neuroscientist Philip Washbourne. “It also gives insight on what is happening in larger, furrier animals.”
The researchers presented their findings in two new articles, PLOS Biology and BMC Genomics.

While social behaviour is a complicated process involving many different sections of the brain, Washbourne’s group has previously found a collection of neurons in the zebrafish brain that are essential for one type of social interaction. If two zebrafish see each other via a glass barrier, they will normally approach and swim side by side. However, zebrafish lacking these neurons show little curiosity.
The scientists discovered a route connecting microorganisms in the gut to these neurons in the brain. Gut microorganisms stimulated cells called microglia in healthy fish to prune back excess connections between neurons.

Pruning is a natural element of brain growth. Extra brain connections, like clutter on a counter, can get in the way of the ones that truly important, resulting in jumbled information.
The trimming did not occur in zebrafish without particular gut microorganisms, and the fish had social deficiencies.
“We’ve known for a long time that the microbiome has a lot of effect on development,” Washbourne said. “However, there hasn’t been a lot of specific research on how the microbiome affects the brain. We’ve done a lot to push the envelope there.”
In a subsequent study, the researchers found two distinguishing characteristics of this group of social neurons that may be shared by mice and zebrafish.

One possibility is that these cells may be recognised by turning on comparable genes, indicating that they may play similar roles in both species’ brains. These hallmark indicators might be utilised to identify neurons that fulfil this function in various brains. The other finding is that “neurons with the same gene signature in mice are in about the same brain regions as zebrafish social neurons,” according to Eisen.
This discovery reinforces the researchers’ conviction that their work in zebrafish may be applied to mice or humans. Scientists can see neural networks grow through the juvenile fish’s translucent bodies, making it easier to examine the nuts and bolts of brain development in zebrafish.

Researchers might then apply what they’ve learned from zebrafish to better understand other species.
Both disturbance of the gut microbiota and inadequate brain synapse pruning have been related to a variety of neuropsychiatric diseases such as autism spectrum disorder.
“If we can connect them, it might lead to better therapies for a wide spectrum of illnesses,” said Joseph Bruckner, a postdoc in the Eisen and Washbourne laboratories and the paper’s first author in PLOS Biology. His next step is to figure out what chemicals connect the bacteria to the microglia, and to trace the connection between microorganisms and behaviour in greater detail.