The Host, its Microbiome and their Aspergillosis.
By GAtherton

Infection

For a very long time, medical science has assumed that infectious diseases are caused by the presence of a pathogen and weakness in the infected person or the host as it is often known, which allows the pathogen to grow and infect. The weakness could be for example a weakened immune system caused by a genetic illness or immune-suppressive treatment such as is used for transplant patients.

We assumed that inside our bodies there was mostly a sterile environment, and one reason we might become ill could be a pathogen getting into one of those sterile areas and then growing uncontrollably. One of those sterile area’s was our lungs – so 30-40 years ago most would have concluded that aspergillosis was caused by an Aspergillus spore getting deep into the lungs of the recipient and then managing to grow.

 

Microbiome

Around the year 2000 we started to be able to look at our internal spaces in more detail and identify any microbes that might be present, What was found was a surprise, for example, we could find many microbes; bacteria, fungi and virus’ growing in our lungs without causing any harmful symptoms. It is common to find Aspergillus fumigatus (ie the pathogen that we assume causes aspergillosis most of the time) present in the lungs of most of us where it lives without causing aspergillosis. How is that possible and what is the difference between that situation and the allergy & infections caused in the lungs of an aspergillosis patient?

We quickly learned that microbes could establish harmless communities, living in harmony with each other and with our immune system. This community was named the human microbiome and included all microbes who live within and on us. Huge numbers live in our gut, especially in our large intestine which is the last section of our digestive system to receive our food before it is ejected via the rectum.

 

Our Microbial Friends

It has emerged then that A. fumigatus can be controlled by its microbial neighbours (our microbiome) working in a tightly controlled partnership with our immune system.

The fungal pathogen interacts with the host to calm the host’s response to the pathogen and uses parts of the host’s immune system to do this. In this way the host and pathogen tolerate each other and do little harm, however, it has been demonstrated that if parts of the host’s fungal recognition system are not working then the host will initiate an aggressive inflammatory response. This is not unlike the situation in ABPA where one of the major problems is the host over-responding to the fungus.

We are also given an example of the microbiome controlling the host’s immune response to a fungal pathogen. Resistance to infection can be increased by the microbial population in the gut sensing a signal – presumably in food ingested by the host. This means that environmental factors can influence the rejection of a pathogen by its microbial neighbours – the message we might take from this is to look after our gut microbiome, and it will look after us. This also holds for the microbes in our lungs, where we have seen differences in the types and location of bacteria in the upper and lower airways that seem to be consistent with the microbiome controlling inflammation – the authors speculate that we need to look at what happens when we challenge these lung microbiotas with a highly inflammatory pathogen such as Aspergillus fumigatus.

The microbiome is also self-regulating as long as it is kept healthy. Bacteria can attack fungi, fungi can attack bacteria in an ongoing battle for food. Host pathogens can be eliminated completely from the microbiome by other microbes.

Different microbiomes in a different part of our body can interact and control diseases such as asthma (ie. lung microbiome interacting with gut microbiome) – so what you eat may influence the microbes in your gut microbiome and that can have an impact on your asthma, for example.

 

I must warn you that lots of the observations mentioned above are based on very few experiments so far, and mostly on animal model systems and Candida rather than Aspergillus so we must be cautious in our interpretation with regard to aspergillosis, however there are a few take-home messages worth bearing in mind.

  1. Most healthy people seem to have very healthy, highly diverse microbiomes – so look after yours with a well-balanced diet containing lots of plant material, lots of fibre
  2. Researchers seem to be turning our assumptions of what infection is on its head – they seem to be saying that inflammation causes infection, rather than infection causes inflammation.
  3. What you eat can have a direct impact on the amount of inflammation your body uses in response to what it perceives as a pathogen.

It can’t be that diseases like asthma and ABPA are caused by an unhealthy microbiome can it?

Current research seems to be suggesting that it may play a part, so the value of someone with aspergillosis doing what they can to promote a healthy community of microbes within themselves cannot be overstated.

What should I eat for a healthy microbiome? (BBC website)

Human Microbiome Project

Microbiome-mediated regulation of anti-fungal immunity