Dr. Amine Zorgani on Novel Microbiome Therapies and Vaginal Health

Today we are joined by Dr, Amine Zorgani, a seasoned microbiome expert. Join us as he brings some interesting and novel microbiome research topics to light such as Live Biotherapeutic Products, Reproductive and Infant Health, Bacterial Vaginosis, vaginal health, and much more. This conversation is a must-listen!

Dr. Amine Zorgani's Story

Dr. Amine Zorgani has had an unorthodox path of growth. He was born in Algeria and is an engineer by training. His engineering degree is more from a microbiology and biotech perspective where he strives to understand how to build bioreactors to produce microbes. One of the first microbes he worked on was from the Sahara desert. His goal was to understand how these microbes can live in places like that. He tried to understand, from a molecular perspective, the proteins that these bacteria produce. He was looking from a bioinformatic perspective but unfortunately in Algeria, there was not that much interest in bioinformatics or like technologies – so he ended up in France where he did a PhD in microbiology. 

At this time, he was trying to find new antibiotics against specific microbes that can affect the health of neonates. This was the whole objective of his PhD and in the first few months of schooling, his PhD supervisor came to him and said, “This is the future of health and medicine.” and he gave me a book about probiotics and prebiotics. This was in 2013 and he had no idea about probiotics and prebiotics but his supervisor said to learn it and thank him later. This started his journey with the microbiome. He went from trying to kill microbes to trying to preserve them. He now tries to save microbes as much as he can because he believes that they are the essence of our existence and are the things that keep us and everything around us healthy. We should do our best to keep some of the microbes intact.

When I look at your LinkedIn posts, you have this beautiful way of summarising very complex microbiome research. I can tell you are so passionate about the microbiome because of these posts. -Kriben Govender

Dr Amine's Passion for the Microbiome

I think if you are a microbiologist and you have at least discovered what the microbiome is, I cannot understand how people can turn away from that. Once you dig into it, it is impossible to say “Okay I am not interested in this anymore.” There is so much to learn and although the first human microbiome project was launched in 2007, we still do not know much about it. We have worked on the microbiome for decades and we only have three approved microbiome-based therapies. There is still so much to be done and the therapies we do have are not complex. We are talking about taking stool from a healthy person and giving it to someone who has CDI (Clostridium difficile infections), this was practiced for centuries, it is not that complex. 

We need to develop microbes that can target specific diseases or cancer cells. We are still a long way away from this but I am always looking for that little idea somewhere. When I share a post on LinkedIn, I am trying to inspire someone else in the world to start some ideas. I hope to inspire at least one person a day which enables me to be happier. Creating the posts also help to engrave this information into my brain because then I will never forget it.

Most people might not know that the reason why I started this podcast was to selfishly learn from experts. I think the motivation is very honourable because you are trying to summarise very complex research paper into some simple actionable steps for someone. This is a win for you and the world. -Kriben Govender

From Engineering to Microbiome Research (Advice for Students)

In my mind, this was always planned out for me. Unfortunately in University, there are key skills that we do not learn. In my opinion, three of the most important skills that all PhD students should be learning today are:

1. Project management: When you are working in a startup or any company, you have to manage projects accurately. 

2. Communication: You have to be able to clearly communicate your ideas to all different types of people. If you have to talk to the Chief Financial Officer, they probably do not know what a microbe is, so you have to have a language that is adapted to these people to enable them to see the essence of your work in the lab. This is so you can get the necessary funding to do your job because if not, you will not be able to create your ideas.

3. Marketing: When you create something, you need to be able to market that idea properly. There is a difference between marketing and communication. With marketing, you are trying to sell and with communication, you are trying to inform someone about it.

In my PhD, I noted that the microbiome is something that is far beyond what I thought and I wanted to get into a startup to harness the microbiome. I ended up in this startup in Ireland called Neritas. We were using artificial intelligence to find peptides from plant proteins. The peptide is the small pieces of proteins that we were trying to identify using artificial intelligence. We were looking at all different types of plants, because every plant has proteins in them, and we wanted to see the beneficial effect of peptides.

One of my departments was looking at the benefits of these peptides on the gut microbiome. When you hydrolyse those proteins with enzymes and drink them, they land on the gut and we wanted to see the impact of this. From then on, I never looked back. We still only know 5% of what we can learn about the microbiome. 

I completely understand where you're coming from, because the microbiome is so undiscovered. There is so much more to learn and from that learning comes the opportunities to develop technology, therapeutics, and solve so many other problems in the world when it comes to health. -Kriben Govender

Approved Microbiome Based Therapies 

The first microbiome-approved therapy is probiotics. This one has a lot of debate and nonbelievers but not all probiotics are the same. Not all of them work and then we have the issue of marketing and communication. There are a lot of probiotics being marketed as probiotics. I saw in the pharmacy that there were activated and inactivated probiotics. The problem with this is that by definition, a probiotic is a live microbe. If it is inactive or “killed” then it is not a probiotic. It may be a postbiotic but the marketing around it was incorrect. So many people are misinformed and that is why there are many nonbelievers.  

With probiotics, there are many different types of strains as well. With each strain comes a different usage and background. When you find the name of the bacteria, the numbers or letters behind that define the strain. We need to find specific strains for specific things that can clinically help you.  

Then we go to another level of complexity which is the therapeutic application. This is where we speak about Live Biotherapeutic Products (LBP). These are single strains (or a combination of different strains) that are intended to treat specific diseases such as IBS and cancer. There is not a single LBP that is currently approved in the market, we are still in phases one and two of the research phase.  

Then we can also look at faecal microbiota transplantation (FMT). This is where we try to find healthy donors and run them through a battery of tests to assess the integrity of their microbiome so that we can transfer them to people who are not healthy and are suffering from various diseases. Today we have an approved product in the FDA and also in Australia for CDI and treatment for many other diseases like autism are in development. CDI treatment is the only one that is approved but the future looks bright for FMT.  

Parallel to FMT, we see other applications from human donors including vaginal microbiota transplantation (VMT). This is where we take vaginal fluids from healthy women and give them to women who have bacterial vaginosis. In a recent paper, there was a story about a woman who was having bacterial vaginosis and recurring pregnancy loss. So they transferred vaginal fluid from a woman that was healthy to this woman and she got pregnant after five months, it was one of the most amazing stories I had ever heard.  

I have friends in this space who have been trying to conceive for many years, unsuccessfully. So when you talk about things like this, it makes me a little bit emotional. Thank you so much for sharing that amazing, cutting-edge research that's happening right now in the world of the microbiome. - Kriben Govender

How are Live Biotherapeutic Products Administered

It depends on the therapy. Within FMT, there are at least two versions of this. In the beginning, we would get the stool samples, homogenise them, then dilute them to be put in a syringe and put them in the anus to inject them into the colon. The other application was during endoscopy. The technology has been developed so now we can freeze and dry the stools to render them into a powder format to be put into a capsule. This is a much more convenient way to take them. We now have syringe injections, endoscopies, and companies developing these pills.

Novel Microbiome Technologies for Women and Infants 

I am extremely happy to see that today we are considering women’s health and infant health when we are developing different therapeutics for applications and diseases. Women are the ones conceiving and bringing happiness to this world and I think they deserve more attention. I try to push research relevant to women's health whenever I come across it. For so long it was neglected and many companies will say that they do not have much of a return on investment in women’s health. Many will focus on fertility because there is a lot of money in this but when it comes to bacterial vaginosis or other recurring infections, there is not much invested into this. We do have some companies stepping up to create products in this space and I hope that my message reaches investors to put more money into women’s health.  

Infant health is also another area we need research in because we know that the microbiome is shaped in the first five years - which shapes our immunity and how we think. It is very important that we seed the correct microbiome that enables us to stay healthy as we grow. I am happy to see more companies in this space. 

Something else that I believe has been taken from the wrong space is microbiome testing. We have a lot of companies selling these tests and some are good but some are not. If you would like to test someone's microbiome, you have to be able to see what you can offer afterward. This is a race against data and I am happy to see that some institutions are trying to use the microbiome testing to advance the microbiome research and not for commercial purposes.  

This enables us to see beyond what we are already seeing here. In my opinion, what is going to change the history of the microbiome is not what bacteria are in there but rather what metabolites they're producing. I think the first company or person who manages to understand why the bacteria are where they are, why they are, and what human pathways they are illuminating or triggering - is going to be a game-changer. We do not yet understand why specific bacterium is there and why it is there now. 

Completely agree. I think that the microbiota signatures are highly individualised almost like a fingerprint. But as you mentioned earlier, there are consortiums or quorums of bacteria that are doing something beneficial in the body, and that's where the research is exploring. What are these metabolites they are producing how do they react with the body? How do they react to disease pathologies? - Kriben Govender

Synthetic Biology in Microbiome Research 

This is a controversial area because many people think that if we take a microbe that naturally exists and then do genetic engineering – we would be introducing GMOs into the body and we might lose track or control of that microorganism and what it does. This is the fear for people who do not understand how genetic engineering works and how stable it can be.  

I engineered microbes for 3 years during my PhD because this is how we study microbes. For example, let’s say that a microbe is degrading iron, if you would like the understand how the microbe degrades iron you would try to identify the gene that codes the proteins for the degradation of iron. You remove those genes with genetic engineering and see whether the microbe loses its ability to degrade iron or not – this is what we call genetic engineering. You can also do this the other way around and put more genes into the microbe and see what it can do.  

I think the controversy today is if we do engineer microbes and release them into nature, we will be introducing something that does not exist in nature and we might lose control of it. But if you do this the right way, meaning that you insert something into the gene of the bacteria that is stable for generations, there is no way a bacterium can reverse engineer what you have done. This can only happen unless you give them the tool. However, the problem is that we do not know if the bacteria have this tool inside of the body. (Plasmid transfer).

Even though we are not sure about this yet, genetic engineering is one of the most fascinating tools that has been invented. It has even received a Nobel Prize from Emmanuelle Charpentier and Jennifer Doudna on the CRISPR/Cas9 genetic scissors. Which was also invented from the bacterium in the first place. I think if we manage to find the right tools to be able to turn the plug off and on, on demand, then the risk is mitigated. We need a way to prevent the microbe from going rogue and getting insane in the body. I still need more data to see if I am on board with this.  

Dr. Amine has given us so much information to think about and make sure to follow him on LinkedIn to learn even more. Be on the lookout for further research into these fascinating topics and share this with a friend who would be interested to learn more!