25 June 2020

Revealing the secrets behind the micro-organisms living inside us

For some years now we have been aware of the fact that human cells live alongside a huge array of micro-organisms inside our bodies, mainly in the digestive tract and the skin, but also inside the reproductive and respiratory systems. 

However, over the course of the last decade we have discovered the fundamental role that this collection of microscopic beings — otherwise known as the ‘microbiome’ — plays in our health. We spoke to two experts in this field, Roger Paredes and Bernat Ollé, both researchers and ”la Caixa” Fellows. They discussed what we currently know about the microbiome and how it could lead to revolution in how we prevent and treat diseases. 

The microbiome against HIV

“The intestine is filled with thousands of species, mainly bacteria. Most of them cannot be cultivated in a laboratory and, as such, there was no way of studying them for a long time. Now, thanks to new DNA sequencing techniques, we have now discovered 80% of these micro-organisms. There are still 20% of them that need to be classified, which are still a mystery” said Roger Paredes, who received a fellowship from the ”la Caixa” Foundation in 2004 to continue his post-doctoral studies at Harvard Medical School in Boston, USA. He is currently working as main researcher in Microbial Genomics at IrsiCaixa, where he is looking into the role that the gut microbiome plays in the pathogenesis of HIV infection and chronic inflammation. 

Roger Paredes. Credit: IrsiCaixa.

What we do know is that micro-organisms play a role in nutrition. “We believe that they have a higher metabolic capacity than the liver. Just picture it: it is as if we have discovered a new organ that performs many different functions. We’re now at a stage where we're looking at the extent to which it affects different physiological processes,” Paredes added. 

However, its activity is not just confined to what goes on in the digestive tract, it goes much further. Human immunity is bound up with the microbiome. At IrsiCaixa, Paredes is researching how these bacteria could help to improve the effects of vaccines for people with HIV and how they could also modulate inflammation processes. “In situations where we are dealing with immunosuppression, such as HIV infection or cancer, the microbiome could have the power to activate our defences. Furthermore, in conditions such as multiple sclerosis or allergic and auto-immune reactions, which we are interested in is specifically the opposite of this: deactivating the immune system slightly, holding it back".

Petri dish with different colonies of bacteria. Credit: Bearwalk Cinema. 

In order to modulate our defences through the microbiome, firstly we need to be completely aware of all the micro-organisms that live in our bodies. “In the coming years, we will be able to analyse the microbiome in such a way that it will be possible to determine the probability of developing certain diseases or how we will respond to different treatments. Changes within the microbiome could be connected with depression, Parkinson’s, Alzheimer’s, etc., We’re just at the start of an enthralling exploration,” said Paredes. 

Drugs for modulating our microbiome

Vedanta Biosciences, a start-up, is one of the first companies to work on designing drugs that target the microbiome. The cofounder and CEO of the company, Bernat Ollé, is a chemical engineer and in 2001 he was awarded a grant from the ”la Caixa” Foundation to complete his PhD and MBA at the Massachusetts Institute of Technology (MIT) in Boston, USA. He told us about how far they have come in designing treatments of this kind. “We are currently able to modify the composition of the microbiome, although this method is still not particularly targeted. It can be done through faecal transplants.” 

However, we have only just embarked on the pathway towards new drugs. “It’s possible that here in the USA the Food and Drug Administration (FDA) will soon legalise the use of a medication for preventing recurring cases of Clostridium difficile, a bacterium that causes serious gut infections that can sometimes be lethal for elderly hospitalised patients. The focus of this drug and others that we are designing here at Vedanta is based on selecting consortia of live bacteria, in other words, species associations that interact with each other in a beneficial way for all of them, and introducing them into the patient orally. They colonise the gut, modify the microbiome and make it less vulnerable to gut infections or inflammation issues".

Bernat Ollé. Credit: Bearwalk Cinema. 

“In the future, we might be able to intercept auto-immune diseases such as ulcerative colitis or Crohn’s disease, as well as type-1 diabetes. I say intercept rather than prevent because we would be able to identify patients who appear healthy but are starting to develop subclinical symptoms of the diseases before they have been diagnosed. In this way, we can intercept the problem at an early stage,” he told us. 

Ollé believes that in the not-so-distant future doctors will be able to work with medicine based on live bacteria derived from the human microbiome. “Traditionally, the pharmaceutical industry has regarded human beings as a collection of targets associated with diseases that are apt to be treated with specific drugs. Drugs connected with the microbiome will help to change this perspective: they will holistically treat the superorganism that we a truly are, made up of the host, in other words Homo sapiens, and the microbes that it harbours, in other words the microbiome.” 

Petri dish with different colonies of bacteria. Credit: Bearwalk Cinema.

“The idea that the health of different communities of beings that live within the same ecosystem, which our bodies are, could be hugely interconnected is a new concept for medicine, but it’s not new in nature,” Ollé added. “For example, by pollinating plants, bees contribute towards their own survival. Then, these plants provide shelter for insects, which in turn are eaten by other species like birds, etc. All of them are interrelated. If anything were to happen to the bees, all the species around them would also be affected".

This interaction also involves what we eat. “As we learn more about interactions with the foodstuffs in our diet, we can start to make more accurate predictions about what combinations of microbes and food are better for a person's health,” he believes. In any case, he pointed out that we are still a long way from reaching such a level of understanding. “As of yet, the only thing we can say is that eating fibre-rich plants and unprocessed food is a good way of keeping a healthy community of gut bacteria. However, we’ve known this for some time".