Category: Gastrointestinal

Categories : Gastrointestinal Immune SystemTags :

Atopic Dermatitis Increases Risk of New-onset IBD

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Adults with atopic dermatitis (AD) have a 34% increased risk of developing new-onset inflammatory bowel disease (IBD) compared to those without the skin condition, according to a new recently published in JAMA Dermatology. The study also shows for children, the risk increase is 44%. Additionally, as the severity of AD increased, the risk of developing IBD rose.

These findings clear up ambiguity from previous research, especially among populations of children and between the different types of IBD: ulcerative colitis and Crohn’s disease. While IBD is located in the gut and AD affects the skin, both diseases are driven by the immune system and are categorised by severe inflammation. Insight offered from this study from the Perelman School of Medicine at the University of Pennsylvania could lead to new treatments for both IBD and AD.

“It is imperative for clinicians to understand atopic dermatitis and the trajectory of our patients with it in order to provide the best standard of care,” said senior author Joel M Gelfand, MD, dermatology professor at Penn. “There are new and better treatments for AD today, and there will likely continue to be more. But providers have to understand how those treatments could impact other autoimmune diseases. For patients with AD and another autoimmune disease, some currently available medications can exacerbate symptoms of their other disease or can help treat two immune diseases at the same time.”

While this is not the first study to explore AD and IBD, its size, with one million adult and child participants with AD drawn from a UK medical database, and its separation between ulcerative colitis and Crohn’s disease advances previous research.

When looking at ulcerative colitis and Crohn’s disease separately, AD was not linked to higher ulcerative colitis in children unless the kids had severe AD. Children with AD, however, had a 54–97% increased relative risk of Crohn’s disease, and among children with severe AD, their risk was roughly five times higher. Results among adults were more straightforward. Adults with AD had a 32% increased relative risk of ulcerative colitis and a 36% increased relative risk of Crohn’s disease. Gelfand notes that the absolute extra risk of developing IBD in individuals with AD is still quite small, but the association is meaningful in better understanding health outcomes in AD. Moreover, since millions of people have AD, this small increase in risk spread among many people is likely important from a public health perspective.

Although Penn researchers did not look at the root cause of IBD linked to AD, they have strong hypotheses about the links.

“AD and IBD can cause changes in the microbiome, chronic inflammation, and the dysfunction in the skin and gut barrier respectively,” said Gelfand, who is also the director of the Center for Clinical Sciences in Dermatology at Penn. “There are also specific cytokines, certain kinds of proteins, that play a role in immune system activity and that seem to be related to AD and IBD. For example, we think dysfunction of types of T cells common to both AD and IBD, could be the culprits. Those need to be explored further to uncover both what’s happening at a microscopic level and what proteins or structures could be targeted to treat one or both conditions.”

As a leading expert on psoriasis, a disease known to be tied to IBD genetically, Gelfand is well aware of how closely skin health can affect other parts of the body. He and his colleagues are also studying AD’s relationship to infections, neurologic and psychiatric disorders, and cardiovascular disease.

“Investigating the relationship between skin diseases and other diseases doesn’t just offer new insight into how these diseases can affect a patient with both, but these studies are especially powerful because they also highlight unique characteristics of each disease and how they behave individually,” Gelfand shared.

Source: University of Pennsylvania School of Medicine

Categories : Cancer GastrointestinalTags :

Gastric Reflux without Oesophagitis does not Increase Cancer Risk

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Reflux disease manifests as acid regurgitation and heartburn and is a known risk factor for oesophageal cancer. However, a new study published in The BMJ by researchers at Karolinska Institutet now reports that the majority of patients do not have a higher risk of cancer. A large-scale study from three Nordic countries shows that the cancer risk is only elevated in patients whom gastroscopy reveals to have changes in the oesophageal mucosa.

“This is a gratifying result since reflux disease is a very common condition and most patients are found to have a completely normal mucus membrane on gastroscopic examination,” says the study’s first author Dag Holmberg, Karolinska Institutet researcher and resident doctor of surgery at Karolinska University Hospital in Sweden.

In reflux disease, acidic stomach contents leak into the oesophagus. This can sometimes cause oesophagitis, inflammation in the oesophageal mucus membrane, which is diagnosed via gastroscopy. It is common knowledge that reflux disease increases the risk of oesophageal cancer, but what the cancer risk is for patients with normal mucosa has remained unknown.

Symptoms generally persist

The symptoms of reflux disease can come and go but generally persist, which means that many patients frequently seek medical attention and often undergo repeated gastroscopies to detect mucosal lesions or prodromal cancer.

“Our study suggests that these repeated gastroscopies are probably unnecessary for people with reflux disease who have a normal oesophageal mucosa,” says Dr Holmberg. “These findings should be reassuring for this large patient group and can guide GPs who often treat them.”

The present study is based on national health data registries in Sweden, Denmark and Finland, and included over 285 000 individuals with reflux disease and no gastroscopic evidence of oesophagitis. The patients were followed for up to 31 years and the researchers registered all cases of oesophageal cancer.

The cancer risk was then compared with that for individuals from the general population matched by age and sex and at the same period in the three countries. No increased risk of oesophageal cancer was observed in patients with reflux disease and a normal mucus membrane.

Increased risk in patients with oesophagitis

By way of comparison, the researchers also analysed the cancer risk in over 200 000 individuals with reflux disease and oesophagitis. These people were at a clearly increased relative risk of developing oesophageal cancer.

“We now intend to examine what factors other than oesophagitis can be linked to tumour growth in people with reflux disease,” says the study’s last author Jesper Lagergren, professor of surgery at Karolinska Institutet.

Source: Karolinska Institutet

Categories : GastrointestinalTags :

Silent but Violent: Taurine-consuming Bacteria Protects the Gut with Toxic Gas

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Photo by Pablo Stanic on Unsplash

Researchers have discovered a new intestinal bacterim that feeds exclusively on taurine and produces the foul-smelling gas hydrogen sulfide. The results, currently published in Nature Communications, show that Taurinivorans muris protects against Klebsiella and Salmonella, two important pathogens.

Chemical warfare in the gut

One of the ways the gut microbiome helps regulated health is in contributing to the levels of hydrogen sulfide – the toxic gas responsible for foul-smelling farts. Having small amounts of hydrogen sulfide in the gut is a good thing; in fact, it’s essential for a number of physiological processes, and can even protect against pathogens. Hydrogen sulfide-producing microbes in the gut may help “choke out” oxygen-dependent pathogens such as Klebsiella, making it harder for them to colonise. However, excessive levels can have negative consequences and have been associated with gut inflammation and damage to the intestinal lining.

Taurine plays yet another a role

The bacterium Bilophila wadsworthia is one of the most important taurine utilizers in humans. In the current study, researchers led by Alexander Loy at CeMESS, the Centre for Microbiology and Environmental Systems Science of the University of Vienna, have discovered a new genus of hydrogen sulfide-producing bacteria in the mouse intestine. “The bacterium we described has a rather unbalanced diet,” explains Loy, “it specialises in consuming taurine.” Taurine is a semi-essential amino acid, synthesised in small amounts in the liver but mostly obtained through the diet – especially meat, dairy and seafood. 

Like hydrogen sulfide, taurine is implicated in a plethora of physiological processes. Recent studies have found a link between taurine and healthy ageing – it seems this nutrient may stave away age-related disease. In light of these findings, the discovery of a new gut microbe that feeds exclusively on taurine (aptly named Taurinivorans muris) is another piece of an exciting puzzle. “By isolating the first taurine degrader in the mouse gut, we’re one step closer to understanding how these gut microbes mediate animal and human health” explains Huimin Ye, lead author of the study. 

To access sufficient taurine in the gut, however, Taurinivorans muris needs the help of other gut microbes to release it from bile acids. Taurine-containing bile acids are produced in the liver and are increasingly released into the intestine during a high-fat diet to help our body digest fats. The activities of the bacteria in the intestine in turn influence the bile acid metabolism in the liver. The results of the Viennese researchers therefore also contribute to a better understanding of these complex interactions in bile acid metabolism, which has an impact on processes and diseases throughout the body.

Taurine-degrading microbes choke out pathogens

One of the most important functions of the symbiotic microbes in the gut is to defend against pathogens. The microbiome has a versatile arsenal of protective mechanisms – and utilising taurine to create hydrogen sulfide is one of them. “Hydrogen sulfide may suppress the oxygen-dependent metabolism of some pathogens,” explains Ye. In the present study, the researchers found that Taurinivorans muris has a protective role against Klebsiella and Salmonella, two important gut pathogens. “The protective mechanism of Taurinivorans muris against pathogens may be via hydrogen sulfide but is essentially not yet fully understood” adds Alexander Loy. Taurine is one of the most important sources of hydrogen sulfide production in the gut. The study thus generates basic knowledge on the physiological interactions between the different gut microbes and their hosts, which is necessary to develop new microbiome-based therapies.

Source: EurekAlert!

Categories : GastrointestinalTags :

Turmeric as Effective as Omeprazole for Treating Dyspepsia, Comparative Study Suggests

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A natural compound found in the culinary spice turmeric may be as effective as the proton pump inhibitor (PPI) omeprazole for treating indigestion symptoms, suggests the first study of its kind, published online in the journal BMJ Evidence-Based Medicine.

Turmeric is derived from the root of the Curcuma longa plant. The spice contains a naturally active compound called curcumin thought to have anti-inflammatory and antimicrobial properties, and has long been used as a medicinal remedy, including for the treatment of indigestion, in South East Asia. 

But it’s not clear how well it compares with conventional drugs for this indication, largely because there have been no head to head studies.

The researchers therefore randomly assigned 206 patients aged 18–70 with recurrent upset stomach (functional dyspepsia) of unknown cause, recruited from hospitals in Thailand between 2019 and 2021, to one of three treatment groups for a period of 28 days.

These were: turmeric (two large 250mg capsules of curcumin 4 times a day) and one small dummy capsule; omeprazole (one small 20mg capsule daily and two large dummy capsules 4 times a day; and turmeric plus omeprazole.

PPIs such as omeprazole are used to treat functional dyspepsia, the symptoms of which include postprandial fullness, early satiety, and pain and/or epigastric pain.

But long term use of PPIs has been linked to increased fracture risk, micronutrient deficiencies, and a heightened risk of infections, note the researchers.

Of the 206 patients enrolled, 151 completed the study, with 20 in the curcumin group;19 in the omeprazole group; and 16 in the combined treatment group, dropping out. 

Patients in all three groups had similar clinical characteristics and indigestion scores, as assessed by the Severity of Dyspepsia Assessment score or SODA, at the start of the trial. Patients were reassessed after 28 days and then again after 56 days.

SODA scores indicated significant reductions in symptom severity by day 28 for pain (−4.83, –5.46 and −6.22) and other symptoms (−2.22, –2.32, and −2.31) for those in the combined, curcumin alone, and omeprazole alone groups, respectively. 

These improvements were even stronger after 56 days for pain (−7.19, –8.07 and −8.85, respectively) and other symptoms (−4.09, –4.12 and −3.71, respectively). 

SODA also captures satisfaction scores: these scarcely changed over time among the curcumin users, which might possibly be related to its taste and/or smell, suggest the researchers.

No serious side effects were reported, although liver function tests indicated some level of deterioration among curcumin users carrying excess weight, note the researchers.

They acknowledge the small size of the study, as well as several other limitations, including the short intervention period and lack of long-term monitoring data. Further larger, long term studies are needed, they say.

Nevertheless, they conclude: “This multicentre randomised controlled trial provides highly reliable evidence for the treatment of functional dyspepsia,” adding that “the new findings from our study may justify considering curcumin in clinical practice.”

Source: EurekAlert!

Categories : Cancer GastrointestinalTags :

Statins Might Reduce the Risk of Colorectal Cancer in Those with Ulcerative Colitis

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Photo by Towfiqu Barbhuiya on Unsplash

New research published in eClinicalMedicine suggests that statins might protect patients with ulcerative colitis from developing and dying from colorectal cancer. The study, by Karolinska Insitut researchers, also found that statin treatment was associated with a lower risk of death regardless of cause in patients with ulcerative colitis or Crohn’s disease.

First author Jiangwei Sun notes that previous studies have shown that the risk of colorectal cancer in patients with IBD, such as ulcerative colitis and Crohn’s disease, is 50% higher than in the general population. This is likely to be because of the chronic gut inflammation that these patients have. Researchers have long sought drugs that can reduce the inflammation-related cancer risk.

“Even though more studies are needed to confirm our results, our study suggests that statins can prevent colorectal cancer in patients with inflammatory bowel disease (IBD), which is a high-risk group for this kind of cancer,” says Dr Sun.

The observational study conducted by Dr Sun and his colleagues compared over 10 500 IBD patients from around the country, of whom half were statin users; the other half of the group, who were matched with the first, were not. After a follow-up period of, on average, 5.6 years, 70 of the statin group and 90 of the non-statin group had been diagnosed with colorectal cancer.

The effect increased over time

The protective effect was directly proportional to the length of time the patient had been on statins and could be demonstrated after two years’ treatment.

There were also fewer deaths from colorectal cancer in the statin group (20) than in the non-statin group (37) during the study period, and deaths regardless of cause (529 versus 719).

The study shows that some 200 IBD patients need to be treated with statins to avoid one case of colorectal cancer or death from the cancer within ten years of treatment onset. The protective effect was only statistically valid for patients with ulcerative colitis.

“We think this is because the study contained fewer patients with Crohn’s disease,” explains Dr Sun. “More and larger studies compiling data from patient populations in many countries will probably be needed to achieve statistical significance for Crohn’s disease.”

Significantly fewer deaths

To avoid death regardless of cause during the same ten-year period, the number of treated patients dropped to 20, on account of how statins also protect against more common conditions, such as cardiovascular disease. Statins were linked to fewer deaths in both ulcerative colitis and Crohn’s disease patients.

The study was based on the ESPRESSO-cohort, which is run by its initiative-taker Jonas F Ludvigsson, paediatrician at Örebro University Hospital and professor at Karolinska Institutet, and the study’s last author.

“In that we can combine tissue data from patients with colorectal cancer with data from Swedish health registries, we’re uniquely placed to study the long-term effects of drugs for IBD,” he says. “Our hope is that these studies will improve the care of IBD patients.”

The most solid evidence so far

According to the researchers, the new results provide the most solid evidence so far that statins could be an effective prophylactic for colorectal cancer among people with IBD. However, more knowledge must be gathered before the treatment can be recommended in general guidelines.

“More studies are needed to ascertain if there is a causal relationship, at what point of the pathological process statins should be administered, what a reasonable dose would be and how long treatment needs to last if it’s to be of benefit,” says Dr Sun.

Source: Karolinska Institut


Categories : Cancer GastrointestinalTags :

How High-fat Diets Affect Gut Bacteria and Increase Colorectal Cancer Risk

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

The increasing rate of obesity and high-fat diets are suspected to be behind the growing rates of colorectal cancers in people aged under 50. Now, in a study published in Cell Reports, researchers at have discovered how high-fat diets can change gut bacteria and alter digestive molecules called bile acids that are modified by those bacteria, predisposing mice to colorectal cancer.

In the study, researchers from the Salk Institute and UC San Diego found increased levels of specific gut bacteria in mice fed high-fat diets. They showed that those gut bacteria alter the composition of the bile acid pool in ways that cause inflammation and affect the replenishment rate of intestinal stem cells replenish.

“The balance of microbes in the gut is shaped by diet, and we are discovering how alterations in the gut microbial population (the gut microbiome) can create problems that lead to cancer,” says co-senior author and Professor Ronald Evans, director of Salk’s Gene Expression Laboratory. “This paves the way toward interventions that decrease cancer risk.”

In 2019, Evans and his colleagues showed in mice how high-fat diets boosted the overall bile acid levels. The shift in bile acids, they found, shut down a key protein in the gut, the Farnesoid X receptor (FXR). and increased the prevalence of cancer.

However, there were still missing links in the story, including how the gut microbiome and bile acids are changed by high-fat diets.

In the new work, Evans’ group teamed up with the labs of Rob Knight and Pieter Dorrestein at UC San Diego to examine the microbiomes and metabolomes (collections of dietary and microbially derived small molecules) in the digestive tracks of animals on high-fat diets. They studied mice genetically more susceptible to colorectal tumours.

The scientists discovered that although mice fed high-fat diets had more bile acids in their guts, it was a less diverse collection with a higher prevalence of certain bile acids that had been changed by gut bacteria. They also showed that these modified bile acids affected the proliferation of stem cells in the intestines. Without frequent replenishment, they accumulate mutations – a key step toward encouraging the growth of cancers, which often arise from these stem cells.

“We are only just beginning to understand these bacterially-conjugated bile acids and their roles in health and disease,” says co-author Michael Downes, a staff scientist at Salk.

There were also striking differences in the microbiomes of the mice on high-fat diets: the collections of gut bacteria in these mice’s digestive tracts were less diverse and contained different bacteria than the microbiomes of mice not on high-fat diets. Two of these bacteria – Ileibacterium valens and Ruminococcus gnavus – were able to produce these modified bile acids.

The scientists were surprised to discover that a high-fat diet actually had a greater impact on the microbiome and modified bile acids than a genetic mutation that increases cancer susceptibility in the animals.

“We’ve pinpointed how high-fat diet influences the gut microbiome and reshapes the bile acids pool, pushing the gut into an inflamed, disease-associated state,” says co-first author Ting Fu, a former postdoctoral fellow in the Evans lab.

The researchers believe high-fat diets change the composition of the microbiome, encouraging the growth of bacteria like I. valens and R. gnavus. In turn, that boosts levels of modified bile acids. In a vicious cycle, those bile acids create a more inflammatory environment that can further change the makeup of gut bacteria.

“We’ve deconstructed why high-fat diets aren’t good for you, and identified specific strains of microbes that flare with high-fat diets,” says Evans, March of Dimes Chair in Molecular and Developmental Biology. “By knowing what the problem is, we have a much better idea of how to prevent and reverse it.”

In the future, the team will study how quickly the microbiome and bile acids change after an animal begins eating a high-fat diet. They also plan to study ways to reverse the cancer-associated effects of a high-fat diet by targeting FXR – the protein that they previously discovered to be associated with bile acid changes.

Source: Salk Institute

Categories : Gastrointestinal NeurologyTags :

Possible Dementia Risk from Long Term Proton Pump Inhibitor Use

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People who take proton pump inhibitors for acid reflux four-and-a-half years or more may have a higher risk of dementia compared to people who do not take these medications, according to new research published in Neurology.

Acid reflux is when stomach acid flows into the oesophagus, usually after a meal or when lying down, resulting in heartburn and ulcers. People with frequent acid reflux may develop gastroesophageal reflux disease, or GERD, which can lead to cancer of the oesophagus. Proton pump inhibitors reduce stomach acid by targeting the enzymes in the stomach lining that produce that acid.

“Proton pump inhibitors are a useful tool to help control acid reflux, however long-term use has been linked in previous studies to a higher risk of stroke, bone fractures and chronic kidney disease,” said study author Kamakshi Lakshminarayan, MBBS, PhD, of the University of Minnesota School of Public Health in Minneapolis, and a member of the American Academy of Neurology. “Still, some people take these drugs regularly, so we examined if they are linked to a higher risk of dementia. While we did not find a link with short-term use, we did find a higher risk of dementia associated with long-term use of these drugs.”

The study included 5712 people, aged 45 and up, without dementia at the start of the study. They had an average age of 75.

Researchers determined if participants took acid reflux drugs by reviewing their medications during study visits and during yearly phone calls. Of the participants, 1490 people, or 26%, had taken the drugs. Participants were then divided into four groups based on whether they had taken the drugs and for how long, as follows: people who did not take the drugs; those who took the drugs for up to 2.8 years; those who took them for 2.8 to 4.4 years; and people who took them for more than 4.4 years.

Participants were then followed for a median duration of 5.5 years. During this time, 585 people, or 10%, developed dementia.

Of the 4222 people who did not take the drugs, 415 people developed dementia, or 19 cases per 1000 person-years. Person-years represent both the number of people in the study and the amount of time each person spends in the study. Of the 497 people who took the drugs for more than 4.4 years, 58 people developed dementia, or 24 cases per 1000 person-years.

After adjusting for factors such as age, sex and race, as well as health-related factors such as high blood pressure and diabetes, researchers found people who had been taking acid reflux drugs for more than 4.4 years had a 33% higher risk of developing dementia than people who never took the drugs.

Researchers did not find a higher risk of dementia for people who took the drugs for fewer than 4.4 years.

“More research is needed to confirm our findings and explore reasons for the possible link between long-term proton pump inhibitor use and a higher risk of dementia,” said Lakshminarayan. “While there are various ways to treat acid reflux, such as taking antacids, maintaining a healthy weight, and avoiding late meals and certain foods, different approaches may not work for everyone. It is important that people taking these medications speak with their doctor before making any changes, to discuss the best treatment for them, and because stopping these drugs abruptly may result in worse symptoms.”

A limitation of the study was that participants were asked once a year about medication use, so researchers estimated use between annual check-ins. If participants stopped and restarted acid reflux drugs in between check-ins, estimation of their use may have been inaccurate. The authors were also unable to assess if participants took over the counter acid reflux drugs.

Source: American Academy of Neurology

Categories : Cancer GastrointestinalTags :

Study Finds No Evidence of Fungus Link to Pancreatic Cancer

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Four years ago, a report that a common species of fungus might fuel pancreatic cancer offered a promising new view of the deadly disease. But in working to validate the finding, Duke Health researchers have found no such association. In a study published in the journal Nature, the researchers conducted a multi-pronged analysis of data from the earlier study and found no link between the pancreatic microbiome and the development of pancreatic cancer.

“We were intrigued by the original finding, as were many research teams,” said senior author Peter Allen, MD, professor in the Department of Surgery and chief of the Division of Surgical Oncology at Duke University School of Medicine.

“There is a growing body of literature connecting the human microbiome to disease, and this was particularly compelling for pancreatic cancer,” Allen said. “But our findings did not support an association between fungi and the development of pancreatic cancer in humans.”

Allen and colleagues worked to recreate the 2019 findings published in Nature by a different research team. The original study raised hopes that there might be a possible method of preventing pancreatic cancer with the use of antifungals or some other approach to protect from infection.

Focusing on the research team’s original raw sequencing data, the Duke researchers were unable to reproduce the findings. Additional studies, using pancreatic cancer tissue in Duke repositories, also failed to produce the original results.

“We believe our findings highlight the challenges of using low biomass samples for microbiome sequencing studies,” Allen said. “The inclusion of appropriate negative controls and efforts to identify and remove sequencing contaminants is critical to the interpretation of microbiome data.”

Source: Duke University Medical Center

Categories : GastrointestinalTags :

Nanomedicine Stimulates Anti-inflammatory Effects to Ease IBD

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Chronic inflammatory bowel disease (IBD), such as Crohn’s disease and ulcerative colitis, is on the rise worldwide, and current medications have problematic side effects. In the journal Angewandte Chemie, researchers report a new method of treatment, based on nanoparticles which trigger anti-inflammatory effects in the diseased sites in the intestine.

Stomach cramps and severe diarrhoea, often accompanied by significant weight loss, are some of the symptoms repeatedly suffered by patients with IBD, often for weeks at a time. The causes of this condition remain unclear but seem to involve a malfunction of the immune system. A cure is not yet in sight. Current treatments aim to reduce symptoms with anti-inflammatory medications, such as 5-aminosalicylic acid (5-ASA), corticosteroids, and immunomodulators. Their long-term use is not recommended because of their severe side effects, such as a high risk of infection resulting from immunosuppression. A team led by Hee-Seung Lee and Sangyong Jon at the Korea Advanced Institute of Science and Technology (KAIST) has now developed an innovative approach for a medication that can be taken orally and targets the inflamed sites in the gastrointestinal tract, minimizing systemic effects.

The starting point of their approach was the glycocalyx, a carbohydrate-rich layer that coats the cells on the surface of the intestine. Beneficial gut bacteria, which have their own matching glycocalyx, attach to this coating. With diseases from the IBD family, the glycocalyx carbohydrate patterns of inflamed intestinal regions are so altered that pathogenic bacteria can attach and enter the mucous membrane.

The team developed nanoparticles that mimic the glycocalyx pattern. Starting with the five sugar monomers most commonly found in nature, they produced a collection (“substance library”) of different polymer chains that have one, two, three, four, or five of these sugars in random order and composition as side chains. These polymer chains aggregate into nanoparticles. They also attached bilirubin molecules. Bilirubin is a bile pigment that is an antioxidant naturally produced by the body and it has an anti-inflammatory effect.

When administered orally to mice with IBD, some versions of these nanoparticles reduced symptoms significantly better than the drug 5-ASA. Nanoparticles with mannose and N-acetylglucosamine were the most effective. These two sugars increase uptake of the nanoparticles by activated macrophages in the inflamed intestine, and bilirubin very efficiently inhibits the inflammatory activity of these immune cells. The concentration of certain inflammatory cytokines is significantly reduced, the production of anti-inflammatory factors is stimulated, and oxidative stress is reduced. The immunosuppressive effect is limited to the inflamed areas of the intestine, minimising unfavourable systemic side effects.

Source: Wiley

Categories : Diseases, Syndromes and Conditions GastrointestinalTags :

Pathogenic Bacteria Use A Sugar from Intestinal Mucus to Dig Themselves in

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A new study shows the sugar sialic acid, which makes up part of the protective intestinal mucus layer, fuels disease-causing bacteria in the gut. The findings, published in PNAS, suggest a potential treatment target for intestinal bacterial infections and a range of chronic diseases linked to gut bacteria, including inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome and short bowel syndrome.

The research by researchers at the University of British Columbia (UBC) and BC Children’s Hospital, used a mouse model of gut infections.

“Bacteria need to find a place in our intestines to take hold, establish and expand, and then they need to overcome all the different defences that normally protect our gut,” says Dr Bruce Vallance, a professor in the department of paediatrics at UBC and investigator at BC Children’s Hospital. “In the future, we can potentially target this sugar, or how pathogens sense it, to prevent clinically important disease.”

Inflammatory diseases such as IBD are on the rise in children, who are more susceptible to gut infections because of their immature immune systems. Dr Vallance and his team sought to understand what enables these bacterial pathogens to survive and expand inside our intestines.

For the study, the researchers examined Citrobacter rodentium, an intestinal bacterial pathogen of mice that’s used to model infections with human E. coli. The team discovered that the bacteria have genes involved in sialic acid consumption, and when these genes are removed, the bacteria’s growth is impaired.

Further investigation revealed that upon consuming the sugars, the bacteria produced two special virulence proteins that help the bacteria cross the colonic mucus layer and stick to the underlying epithelial cells. The findings reveal how the bacteria can change over time and actually worsen disease.

“You start off with IBD, your microbes change, they start digging their way into the cells lining your gut, causing more inflammation, and that may be one reason why IBD becomes chronic,” says Dr Vallance. “Specific nutrients such as sialic acid or other sugars might be the Achilles heels for them in terms of things you could target to remove dangerous bacteria from the intestine.”

Dr Vallance and his team are now examining the role other sugars in the gut may play in feeding pathogenic bacteria. They’re also looking for probiotics that could outcompete the dangerous bacteria, stealing the sugars away from them.

They also plan to explore potential interactions between resident and pathogenic bacteria. Pathogenic bacteria can’t access the sugars on their own and thus, some of the normally harmless resident bacteria must serve as accomplices.

“Basically, these accomplices cut the sugar off the mucus, and then either they hand it to the dangerous bacteria or the dangerous bacteria have come up with a way of stealing it from them,” he explains.

A better understanding of these interactions could provide new ways to block pathogenic bacteria, something Dr. Vallance says is urgently needed.

“In the past, our ancestors were constantly assaulted by dangerous bacteria,” says Dr. Vallance. “With the advent of more and more antibiotic resistance in bacteria, these bacterial infections are going to become a growing problem again. Without new antibiotics, we need to come up with novel ways to fight these bacteria, like starving them.”

Source: University of British Columbia