How do gut bacteria use sialic acid sugars?

24th January 2025

We catch up with Dr Andrew Bell to find out about his Quadram Institute Fellowship focused on how gut bacteria use a certain group of sugars called sialic acids

“My fellowship aims to undertake fundamental research to understand how gut bacteria use specific sugars known as sialic acids.

Sialic acid sugars

Sialic acids and the closely related sugars play a key role in many bacterial cell processes and are essential to the survival of certain bacterial species.

The most common sialic acid, Neu5Ac, is an abundant nutrient source for bacteria in the gut. At the Quadram Institute we have shown that bacteria that are good for the gut can use these sugars giving them a competitive advantage living in the gut.

However, an excess of Neu5Ac in the gut has also been shown to help bad bacteria such as Salmonella which cause infection.

Another sugar which is closely related to sialic acid sugars is called 3-deoxy-D-manno-octulosonic acid (KDO). This has become a target for developing new antimicrobials.

In some species of bacteria, the KDO sugar is essential in forming the outer membranes of cells. In these species of bacteria, removing the ability for cells to make this sugar means that the bacteria cannot survive. The important role of KDO for bacteria cells has, therefore, identified it as a target for developing new antimicrobials.

Similarly, flagella structures, which help some disease-causing bacteria to move, use the sialic acid called pseudaminic acid (Pse). Removing the ability of bacteria to make Pse leads to a much slower movement and migration of bacteria.

Targeting sialic acids for new therapeutics or prebiotics

The importance of sialic acid sugars in key biological pathways of disease-causing bacteria has led to them being a target for new antimicrobials.

However, the studies into how these sugars are used by bacteria have so far been limited to the most common form of sialic acid called Neu5Ac. We don’t know yet what impact there would be on the rest of the bacterial communities present in the gut if KDO or Pse synthesis were targeted by antimicrobials.

We don’t know if sialic acid sugars may be beneficial by promoting the growth of commensal strains of bacteria as so far studies have been limited to disease-causing bacteria.

Additionally, there are over 50 sialic acids known to exist and many are more than likely to find their way to the gut either in our food, or synthesised by the microbes living in our gut.

I’m hoping to learn more about the role of these compounds in the gut by assessing their impact on bacterial communities. To do this I will chemically synthesise a range of these sialic acids with the help of excellent collaborators in the UK and Europe.

I will then ‘feed’ these sialic acid sugars into fermentations simulating the gut microbiome and use sequencing technologies to identify changes to the bacterial communities. This will identify species that benefit from sialic acid sugars and those that do not. From here I will identify species for further analysis and identify pathways for the metabolism of these sugars, which will hopefully lead to exciting discoveries and identification of antimicrobial targets and beneficial prebiotic effects.

Path to independent research

I have always been curious about how things work and always enjoyed and achieved good marks in science subjects, so I decided to undertake an undergraduate degree in biochemistry.

My interest in research was developed during my Year in Industry, spent at the John Innes Centre. Following my Year in Industry I knew I wanted to follow an academic route, but I decided plant science wasn’t for me.

In my final year of university, I discovered the gut microbiome and applied for a PhD with Professor Nathalie Juge at the Institute of Food Research and have been hooked since. Following my PhD and Postdoctoral position at the Quadram Institute I decided to apply for a fellowship to allow me to progress my own research ideas and to develop an independent line of research.

The first look at fellowship applications was overwhelming and I wasn’t sure how I would pull all the relevant information together. But being able to bring your own ideas together and form a project was exciting. Applying for the fellowship allowed me to focus on the science and what I want to achieve.

My advice to anyone thinking of applying is to give plenty of time to the application and plan ahead. Once you get started coming up with, and developing your own project, it isn’t actually as daunting as it first appears. I would also say don’t be afraid to ask for help, you’ve never done this before, and a bit of advice goes a long way. Nathalie was an excellent mentor for me, which definitely made the process smoother.”

 

Related People

Related Targets

Targeting the understanding of the microbiome

Understanding the Microbiome

Related Research Groups

Juge group

Nathalie Juge

Related Research Areas

A green background with an illustration of a gut full of microbes.

Food, Microbiome and Health