New personalized tools to study the interactions between human and microbes – Moran Morelli
Did you know that our body contains more microbes than human cells?
We are composed of trillions of human cells, but we rapidly get colonized by microbes such as fungi, bacteria, archaea and viruses. These microbes form a community called the microbiota and are localized in specific areas of our body such as the skin, gut, and reproductive system. Despite the relevance of the interactions between human cells and microbiome for human health, it is fair to say that we still do not fully understand them.
What are the benefits and drawbacks of this relationship?
Our microbiota benefits us in many ways, such as by helping during digestion or reinforcing our immune systems. However, under specific conditions, some of our inhabitants can become harmful and even lead to life-threatening situations.
This is what can happen in the case of a fungus called Candida albicans, which can cause oral thrush and vaginitis, but also fatal bloodstream infections in hospitalized patients. The occurrence and outcome of these infections depends on the interplay between the fungus, the host's immune system, and the rest of the microbiota. Defining and exploiting this interplay to improve the management of Candida infections is the aim of the European project FunHoMic.
Why are our current tools limited?
To study diseases and find new therapies, researchers use simplified versions of the organs in question. These versions are called models and fall in two major categories:
1. In vitro models (“within the glass”): microorganisms, cells or biological molecules outside of their biological context.
2. In vivo models (“within the living”): whole living organisms such as mice, rats, pigs, and zebrafishes.
Using these tools, researchers can identify potential drug candidates and test whether these are efficient and safe before testing them in humans. However, existing models cannot always replicate efficiently what is happening in the human body. In vitro models, while cost-effective, are sometimes too simplified, whereas in vivo models raise ethical issues. Moreover, many studies using animal models fail to predict what will occur in humans.
What can we do to improve these tools?
In living animals, cells are spatially organized in three-dimensions. They interact with each other and receive nutrients from blood vessels. Different cell types collaborate with each other to execute specific functions.
Therefore, to counter the limitations of current models, we would need to take these parameters into account. That’s why, at MIMETAS, we are working on new easy-to-use tools that recapitulate complex 3D biology. In the framework of the FunHoMic project, we will create new models using different types of human and microbial cells grown in conditions resembling those found in the human body.
What would be the benefits?
As a first step, these new tools would allow researchers to better understand how fungi become harmful. They would solve ethical problems linked to animal testing and allow rapid screening of potential drug candidates.
In a later step, researchers and clinicians would use cells from a patient to re-create mini organs on which they could test which of the available drugs work best for this specific person. Thus, each patient would receive a personalized therapy adapted to his or her needs.
All images created by Fabio Morelli and used here with permission.
Fight Fire with Fire - Nathaniel Cole
The fungus Candida albicans can live harmlessly in our guts but when our immune systems are dampened, or we take antibiotics for other infections for long periods of time, Candida albicans can leave our gut and cause serious infections. Candida can cause thrush in the vagina and in the mouth and can sometimes cause systemic infection by entering the bloodstream. Disease caused by Candida can reduce the quality of people’s lives and in the case of systemic infection is life threatening. Vaginal thrush effects 70% of women at least once during their lifetime and 5% of these women suffer from recurring infections. Systemic infection leads to 70,000 deaths per year and is a major burden on the healthcare system. In addition, the drugs we use to treat infections caused by this fungus sometimes don’t work so its really important to find other ways of preventing infection from Candida living in our gut.
Many of us have heard of the phrase “you can’t fight fire with fire” but in my case that’s not really true. My PhD project is trying to do just that, by pitting microorganism against microorganism. I want to find good bacteria, from our guts, that can fight this fungus and thereby reduce the risk of infection. It’s also really important to understand how these specific bacteria stop Candida albicans from colonising the gut in numbers high enough to cause disease. They could be fighting this fungus with microbial chemical warfare, by producing antifungal products that curtail the growth of fungi like Candida albicans. Or they could be better than Candida at using nutrients in the gut, or munching on Candida cells. Whatever the method, it’ll be my aim to figure it out. This project is part of the FunHoMic consortium which gathers 13 PhD students who are all trying to decipher the dynamic relationship between us, C. albicans and our resident microbes. We aim to use this knowledge to deliver more personalised medicine to patients by identifying those most at risk and offering preventive or therapeutic interventions like my good bacteria!
I’m really excited about my project because if successful, it proves that our friendly neighbourhood bacteria can help defend us against the bad guys, giving us a new avenue to explore to treat infections and reduce our use of antifungal antibiotics. When resistant superbugs strike, we need different tools to combat them. Changing the populations of microorganisms in our guts, using good bacteria proven to have an effect in reducing the risk of disease, is an ingenious way to do this. Fight fire with fire.
Video - Ricardo Martins