Researchers from the Quadram Institute are launching a new project to uncover how bacteria in the gut microbiome make and use vitamin B₁₂. By better understanding the role of this essential micronutrient in the complex microbial community, they hope to be able to find new ways of improving the gut microbiome, ultimately benefitting our health.

The gut microbiome consists of trillions of microbes that interact with each other and the gut lining We are starting to understand how the makeup of that complex community and the nature of those interactions define how the microbiome affects the health of its host – us. Using this knowledge, we can find ways of manipulating the microbiome to optimise its health benefits.

Ruminococcus gnavus (green) in the mucus layer (red) of the gut lining (gut cell nuclei are blue). Image by Dr Laura Vaux, Juge Group, the Quadram Institute

What is crucial to this is not just the species of bacteria, but also how they interact, including how different species share resources between different members of the community, for mutual benefit.

One such resource is vitamin B₁₂. It is critical for fundamental processes in bacterial cell, making it a valuable resource within the microbiome. However, very few bacteria can make it – it’s a large molecule that has a complicated synthesis process that takes up a lot of energy. But those bacteria that can make it have a significant growth advantage, as will any other species that they share it with. But what is the nature of that trade off?

This is the question Professors Nathalie Juge and Martin Warren will answer in this new study, supported by a £500,000 grant from the Biotechnology and Biological Sciences Research Council, part of UK Research & Innovation (UKRI).

Prof. Juge is a world-leading expert in gut microbes and their interactions with the glycan-rich mucus that line the gut. In the work leading to this project, they found that Ruminoccus gnavus, one the model organisms they work with in the lab to study mucin glycan utilisation, needs vitamin B₁₂ to grow whereas strains of Limosilactobacillus reuteri (previously called Lactobacillus reuteri) that are found in the human gut could make vitamin B₁₂. The team has now shown in experiments that growth of R. gnavus can be rescued if L.reuteri is present.

They will collaborate with Quadram colleagues working with Professor Martin Warren, an expert in the biochemistry of vitamin B₁₂ to understand how vitamin B₁₂ is central to their interdependency, and how that benefits us. Martin leads Quadram’s Food Innovation and Health programme.

Prof Juge said ‘I am delighted to be working together with Prof Martin Warren on Vitamin B₁₂ interdependency by two of the model organisms, L. reuteri and R. gnavus we work on in our lab. This collaborative project will allow us to work across programmes to provide chemical and biochemical answers to how bacteria have evolved their complex trade-offs by sharing metabolic burden. We will also exploit these findings to design B12-based strategies to manipulate microbial composition in the gut for the benefit of human health.’

The new project will define the details of this relationship, by working out precisely how L. reuteri synthesises vitamin B₁₂, the exact form of the vitamin it produces, and how R. gnavus then takes up and metabolises it. With this knowledge, the team will then test how well different interventions work in advanced models of the human colon, seeded with human microbiome samples containing little or no vitamin B₁₂. They will compare supplementation with various forms of vitamin B₁₂ alongside addition of B₁₂-producing L. reuteri strains, looking at how well they support a healthy microbiome.

It is hoped that this study will lead to ways that we can all maintain our microbiome to maximise its benefits to health, as well as developing targeted new treatments for specific conditions linked to low B₁₂ status. People with pernicious anaemia, for example, may benefit as they have an impaired ability to absorb B₁₂ from the diet. Plants don’t produce B₁₂, meaning vegans and vegetarians may risk getting insufficient B₁₂ so this project may open up new ways of supporting plant-based diets for maximum gut health.