Disease-Causing Bacteria Munch on Sugar in the Gut

University of British Columbia (UBC) and BC Children’s Hospital scientists discovered that disease-causing bacteria in the gut feed on sialic acid, a sugar found in the intestinal mucus layer. The research is published in the Proceedings of the National Academy of Sciences.

Bacteria feed on sialic acid

An increase in the number of people suffering from inflammatory conditions – such as inflammatory bowel disease (IBD) – has prompted researchers to explore how bacterial pathogens survive and grow inside our gut.

“Bacteria need to find a place in our intestines to take hold, establish and expand, and then they need to overcome all the different defenses that normally protect our gut,” says Dr. Bruce Vallance, an investigator at BC Children’s Hospital and a professor in the department of pediatrics at UBC. The mechanisms harnessed by bacteria to infect the gut – and succeed, in spite of these defenses – are poorly understood.

Vallance led a team of scientists, including UBC research associate Dr. Hongbing Yu in a study that analyzed an intestinal pathogen called Citrobacter rodentium.

“In the last decade, many advances made in the field of intestinal pathogen metabolism and colonization resistance have come from the study of C. rodentium, a murine bacterial pathogen related to the clinically important attaching and effacing (A/E) pathogens enteropathogenic E. coli (EPEC) and enterohemorrhagic E. coli,” the research team describe in PNAS.

Vallance and colleagues used whole-genome sequencing methods to study the bacterial genome, discovering genes that are implicated in the consumption of sialic acid – a type of sugar that makes up part of the protective intestinal mucus layer.

The researchers adopted overlap extension polymerase chain reaction (OE-PCR), a method commonly used to insert mutations into the genome, to delete these genes. They were intrigued to find that, consequently, the bacteria’s growth was limited.

Cutting off sugar supply – a therapeutic intervention?

The scientists conducted in vivo experiments on C. rodentium-infected mice to understand why sugar is so important for the survival of the bacteria. “We showed that sialic acid is captured from the colonic environment via C. rodentium’s sialic acid transporter NanT and thereafter utilized as a growth substrate to expand within the gut,” the team explain. “It also serves as a signal for C. rodentium migration toward mucus, and the sialic acid decorated mucins that comprise it.”

These findings may explain why gut infections can become worse over time. “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 Vallance. “Specific nutrients such as sialic acid or other sugars might be Achilles heels for them in terms of things you could target to remove dangerous bacteria from the intestine.”

Targeting infectious bacteria’s consumption of sugar could open doors for new therapeutic approaches, Vallance explains: “In the past, our ancestors were constantly assaulted by dangerous bacteria. 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.”

Reference: Liang Q, Ma C., Crowley S M, Allaire, J M, et al. Sialic acid plays a pivotal role in licensing Citrobacter rodentium’s transition from the intestinal lumen to a mucosal adherent niche. Proc Natl Acad Sci USA. 2023. doi: 10.1073/pnas.2301115120

This article is a rework of a press release issued by the University of British Columbia. Material has been edited for length and content.