Researchers Unveil Link Between Sugar and Disease-Causing Gut Bacteria

A recent study conducted by researchers at the University of British Columbia (UBC) and BC Children’s Hospital has shed light on sugar sialic acid’s role in fueling gut disease-causing bacteria. Published in PNAS, the findings have significant implications for potential treatment targets in combating 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. 

Dr. Bruce Vallance, a professor in the Department of Pediatrics at UBC and an investigator at BC Children’s Hospital, explains the significance of the research, stating that bacteria need to find a niche in our intestines to establish and expand while overcoming the body’s natural defenses. The study’s findings suggest that targeting the sugar sialic acid, or how pathogens detect and utilize it, could potentially prevent clinically essential diseases. 

Inflammatory diseases, including IBD, are on the rise in children, and their immature immune systems make them particularly susceptible to gut-bacterial infections. Dr. Vallance and his team, including lead author Qiaochu Liang (a graduate student at UBC) and UBC research associate Dr. Hongbing Yu, aimed to uncover the factors enabling bacterial pathogens to survive and increase in the intestines. 

The researchers focused on Citrobacter rodentium, an intestinal bacterial pathogen in mice commonly used to model infections caused by human E. coli. Through their investigation, they identified genes in the bacteria that are involved in sialic acid consumption. Removing these genes impaired the bacteria’s growth. 

Further examination revealed that upon consuming the sugars, the bacteria produced two specific virulence proteins that facilitated their penetration of the colonic mucus layer and adherence to the underlying epithelial cells. This finding indicates how bacteria can evolve, exacerbating disease conditions. 

Dr. Vallance explains that as IBD develops, the composition of microbes in the gut changes, and these microbes begin to infiltrate the cells lining the gut, leading to increased inflammation. This mechanism may contribute to the chronic nature of IBD. He suggests that specific nutrients like sialic acid and other sugars could be targeted to eliminate dangerous bacteria from the intestine. 

Moving forward, Dr. Vallance and his team plan to investigate the role of other sugars in the gut in feeding pathogenic bacteria. They also aim to identify resident beneficial bacteria (probiotics) that can outcompete dangerous bacteria by depriving them of sugars. 

Additionally, the researchers intend to explore potential interactions between residents and pathogenic bacteria. Since pathogenic bacteria cannot access sugars independently, harmless resident bacteria must act as accomplices by providing the sugars. Dr. Vallance elaborates on this relationship, explaining that these accomplice bacteria strip the sugars from the mucus layer and either transfer them directly to the dangerous bacteria or the dangerous bacteria find a way to steal them. 

A deeper understanding of these interactions could lead to novel approaches for blocking pathogenic bacteria, which Dr. Vallance considers an urgent necessity. As he notes, bacterial infections are poised to become a growing problem with the increasing prevalence of antibiotic-resistant bacteria. Without new antibiotics, innovative strategies such as starving bacteria by targeting their sugar sources are crucial for combating these infections.