The microbial community living within our large intestine is a highly dense and complex ecosystem. While some of these microbes cause illness and disease (such as bacteria and viruses), others are friendlier to us and help keep us in good health.
Author
- Lucy Crouch
Research Fellow, Institute of Microbiology and Infection, Department of Microbes, Infection and Microbiomes, School of Infection, Inflammation and Immunology, College of Medicine and Health, University of Birmingham
Akkermansia muciniphila is one of these friendly bacteria.
Researchers have known for years that A muciniphila is associated with good health. One of the important roles it plays in our gut is maintaining the function of our gut barrier. This keeps the bad bugs out while making sure we can still absorb the important nutrients from our diet that keep our cells working as they should. But when there's an imbalance of A muciniphila in the gut, it can lead to problems with our health.
This unusual bacteria lives in our large intestine and survives off of mucin - the layer of mucus that covers the large intestine's surface.
Mucin provides a small but important separation between the human cells and microbial cells that call the large intestine home. If this mucus layer is disrupted, microbes can come into direct contact with the human cells. This may result in inflammation as the human cells react to the bacteria - potentially leading to the development of disease, such as inflammatory bowel disease .
Akkermansia muciniphila is a very fussy eater. It only uses the glycoproteins (molecules containing protein and carbohydrates) in mucin as an energy source . But just how this bacteria extracted energy from glycoproteins was a mystery until recently. Research conducted by myself and colleagues discovered that A muciniphila deploys a range of different enzymes that work together in order to unlock the sugar found in mucin.
Using mucin taken from a pig, we analysed both enzyme activity on the surface of cells alongside their genes to understand which enzymes were involved in breaking the glycoproteins in mucin down.
We discovered that A muciniphila uses 66 different enzymes to extract the important energy it needs from the glycoproteins in order to do its important work. We are the first group to describe this process.
Important for health
Studies looking at A muciniphila's interaction with the immune system in mice have revealed that it calms the immune system down and may prevent obesity and diabetes from developing.
Researchers have highlighted specific peptides (a type of molecule) that it secretes which have this effect on the immune system. Due to its friendly nature and calming effect on the immune system, Akkermansia muciniphila has even been used to develop probiotics .
Researchers have also found that people who have a metabolic disease , such as diabetes or fatty liver disease, have fewer Akkermansia muciniphila in their large intestine. The more lean and athletic you are, the more A muciniphila you have.
Although Akkermansia muciniphila only eats mucus, our diet does still affect it - though indirectly.
Colon-dwelling bacteria such as A muciniphila use the carbohydrates they extract from the fibre-rich foods in our diet as fuel. In return they produce substances called short-chain fatty acids . These compounds feed the top layer of human cells in the colon. In fact, 10% of our energy comes from this process.
Akkermansia muciniphila also supports other bacterial species in the microbiome by giving them broken-up mucus so they can survive - a process known as "cross feeding". But, if we don't eat enough fibre as part of our diet, mucins become a much more heavily used source of nutrition.
This can lead to the depletion of the large intestine's mucus layer - throwing the microbiome's delicate ecosystem out of balance. This increases the chance of developing inflammatory diseases . So, although Akkermansia muciniphila is not a pathogen, it can remove too much mucus under the wrong conditions.
Our research is the first complete example of how mucus is broken down by this bacterial species. It's important to understand this process, as it's key in the way our microbes interact with each other - and with us. The enzymes that we described from Akkermansia muciniphila can now also be used as tools to analyse how these complex mucin structures vary across different body sites and between people.
The more researchers learn about Akkermansia muciniphila and the other microbes that live in the colon, the more we understand the importance of eating a variable, high-fibre diet .
Lucy Crouch receives funding from the Wellcome Trust, Royal Society and the Academy of Medical Sciences.
