The findings suggest a promising target for treating intestinal bacterial infections and various chronic diseases associated with gut bacteria, such as inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome, and short bowel syndrome.
Researchers at the University of British Columbia (UBC) and BC Children’s Hospital have conducted a study revealing that the sugar sialic acid, which forms part of the protective mucus layer in the intestines, actually supports disease-causing bacteria in the gut.
The study, published in PNAS, highlights a potential target for treating intestinal bacterial infections as well as various chronic diseases associated with gut bacteria, including inflammatory bowel disease (IBD), celiac disease, irritable bowel syndrome, and short bowel syndrome.
Dr. Bruce Vallance, a professor in the pediatrics department at UBC and an investigator at BC Children’s Hospital, explains that bacteria need to establish themselves and overcome the natural defenses of our gut in order to thrive. By targeting this specific sugar or how pathogens detect it, it may be possible to prevent significant diseases in the future.
The prevalence of inflammatory diseases like IBD is increasing among children, who are particularly vulnerable to gut bacterial infections due to their underdeveloped immune systems. Dr. Vallance and his team, including UBC graduate student Qiaochu Liang and UBC research associate Dr. Hongbing Yu, aimed to understand the factors that enable these bacterial pathogens to survive and multiply within our intestines.
To conduct their study, the researchers focused on Citrobacter rodentium, an intestinal bacterial pathogen found in mice that are commonly used to model human E. coli infections. They discovered that the bacteria possess genes responsible for consuming sialic acid, and when these genes were removed, the growth of the bacteria was impaired.
Deeper exploration uncovered that when the sugars were ingested, the bacteria generated two distinct virulence proteins. These proteins facilitated the bacteria’s ability to traverse the colonic mucus layer and adhere to the epithelial cells beneath. These findings shed light on the bacteria’s ability to evolve and potentially exacerbate the progression of diseases.
Dr. Vallance explains that in the case of IBD, for example, the microbes undergo changes and begin infiltrating the cells lining the gut, leading to increased inflammation. This understanding suggests that specific nutrients such as sialic acid or other sugars could potentially be targeted to eliminate harmful bacteria from the intestine.
Moving forward, Dr. Vallance and his team plan to explore the role of other sugars in the gut that may contribute to the nourishment of pathogenic bacteria. They are also searching for resident beneficial bacteria (probiotics) that could outcompete the harmful bacteria by depriving them of sugars.
Additionally, they intend to investigate potential interactions between resident and pathogenic bacteria. Pathogenic bacteria are unable to access sugars on their own, so some typically harmless resident bacteria must act as accomplices. These accomplice bacteria extract sugars from the mucus and either pass them to the dangerous bacteria or allow the dangerous bacteria to steal them.
Dr. Vallance emphasizes that gaining a deeper understanding of these interactions could lead to novel strategies for blocking pathogenic bacteria, which he believes is urgently needed.
With antibiotic resistance on the rise, bacterial infections pose an increasingly significant challenge. In the absence of new antibiotics, innovative approaches to combat these bacteria, such as starvation, are necessary, inspired by the constant threats our ancestors faced from dangerous bacteria.
Source: 10.1073/pnas.2301115120
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