Dr Jelena Vulevic on Delaying Ageing using Prebiotics and Postbiotics
How does the gut microbiome influence our immune system?
I first want to say the difference between the microbiome and the microbiota. The microbiome is the collection of genes of the microbiota, which are living organisms present all around us. The microbiota is not only influential when it comes to the immune system but they are the main managers of the immune system. When we are born, we do not have the immune system. We get what we need from our mother's milk if we are breastfed, our environment, and milk formula will also try to help the immune system and provide protection. So especially during those first 40 days of life, when we don't have the immune system, it's the microbiota inside our guts that's driving the protection of the infant against everything that can go wrong.
That is where it starts and throughout our lives, the microbiota manages and constantly interacts with the immune system, the good and the bad. So the connection between the two is very strong and even though they are two different entities, they constantly interact.
The definition of ulcerative colitis and key takeaways from Jelena’s research
Ulcerative colitis is the reason why I decided to study microbiota. When I was a student in 1995, I read some of Hippocrates' work which led me to some studies from a Japanese group in the 1980s. They looked at certain components from the microbiota and these specific components could be involved in colorectal carcinogenesis. But first of all, through the initiation of some inflammatory responses that resemble ulcerative colitis.
Ulcerative colitis is one of two inflammatory bowel conditions, the other being Crohn’s. The main difference between the two is the location. Ulcerative colitis is a lifelong disease and we do not have many treatments - just management of symptoms. The symptoms are pain, bloating, bloody diarrhoea, etc. It is not good to have and the answer to how it starts it not known. There is a strong link between genetics but the question that I have had for 30 years is whether the microbiota reacts to whatever happens within the body in terms of the immune system, and is therefore not so good, or is it the other way around?
Ulcerative colitis and Crohn's disease
Ulcerative colitis always starts at the rectal region and it extends distally from the rectum upwards into the colon. Whereas Crohn's disease could appear anywhere within the gastrointestinal tract. It can be patchy and does not have to affect a continuous region in the gut, you can even get it in your mouth. This makes the treatment of Crohn's disease somewhat more difficult than ulcerative colitis, but they are equally difficult to treat and manage symptoms.
There are some standard medical treatments that you can use to help your symptoms. I am always on the side of lifestyle modification which involves diet. A lot of people who have any form of gastrointestinal disorder will eventually become intolerant to various environmental pollutant factors, including dietary components. So recognition of those and then removal of them is always a good way forward. Plenty of evidence shows that the amount of inflammation that enters the body and, more importantly, the intestinal barrier, influences the microbiota.
People should be trying prebiotics, probiotics, and post-biotics. The only issue is that there are so many things out on the market and we are all so different. So there is a lot of trial and error to see what works for you. We live in a world where everyone expects things to happen yesterday, but when you are dealing with the gut, such a dynamic and huge environment, things can't happen overnight. I always tell people when you start something, give it a month (ideally 3 months) before you decide if it is working for you or not. In the beginning, you can experience symptoms that are not very good but you have to give it longer than a few days or a few weeks.
That is so true. It takes some time to develop these problems, perhaps even a lifetime of poor choices, and then we have this expectation that we're going to solve the problem by taking a pill or some sort of intervention. I completely agree with you that these things take time. - Kriben Govender
Is there a particular signature of organisms that could be used as a marker in the future?
If you asked me that question 10 years ago I would have told you “Yes, there are certain markers.” This is still true but in the last 10 years, there has been so much work done with the microbiome and microbiota. In my experience, it is impossible to define a healthy microbiota. “What compromises a healthy microbiota?” is a question I have spent many years trying to answer and we still cannot answer this basic question. This is because the microbiota is influenced by so many different things and the human is influenced by so many different things. Then you have both of them together and it is very complex.
So until we can answer as to what comprises a healthy microbiota, all the biomarkers that we currently have are useful and we can rely on them. But to apply that knowledge to a population level or every single person suffering from any kind of disorder or disease is very difficult. You can take two people who look identical on paper but they have completely different microbiota.
I have worked with people with ulcerative colitis, whom I followed for a year, and I took their stool samples and analysed their microbiota every month over a year. And during that one year, even in that same person where everything was controlled, including the treatment and the diet, they had very different microbiota makeup.
So answering about particular markers is a difficult question to answer but we do know that certain members of the microbiota are beneficial. You can increase these with diet, lifestyle, and additional functional food ingredients. We also know that certain lifestyles and components of diet are bad so you want to keep those down. These include a high-fat diet, eating too much meat, smoking or drinking too much, and not exercising.
Five years ago, when I came to this realisation, I asked myself the question “What do I do? I've spent all these years trying to modulate the microbiota looking for the healthy microbiota to exert a benefit onto humans and now I've come to this realisation that I'm never going to answer that question. Do I give up and do something else?” And I concluded that I do think that one day we will answer that question but in the meantime, there is a lot we can do because microbiota is influential and we know a lot about it.
The thing that I decided to do with my company VeMico is extract the best benefit from the microbiota and help the needs along with a balanced lifestyle. It does not matter what’s the microbiota and what is the environment, if our immune systems can tolerate what is coming our way and we can increase this tolerance then we can manage everything a lot better. We can do this by extracting the beneficial compounds from the microbiota that we know and have been around for a long time, and bringing them back into the human body without the need to interact with the microbiota. This is the way forward and what post-biotics are. That is why we decided to concentrate on them.
I'm so pleased that you brought that up because it is absolutely on point with the way my thinking is in this current place in time. I think it's really about the metabolites that these microbiota produce, trying to replicate some of these metabolites, and then using them as a personalised nutrition tool. - Kriben Govender
What is a postbiotic?
There are a few definitions and some controversy among those definitions. In simple terms, a postbiotic is what the probiotics produce. These are produced daily in our gut and they are also produced in fermented foods such as kimchi or yoghurt. A postbiotic is the metabolites or the end products. Some definitions say that post-biotic must also contain the components of bacteria or other microorganisms but I think that is going into scientific details that are maybe not that important.
What is Beta GOS?
Beta Galactooligosaccharide (Beta GOS) is a prebiotic. There are lots of prebiotics on the market and a lot of them in food as well. I have spent a lot of time working with all sorts of prebiotics and Beta GOS’s only naturally occur in human breast milk and even then, they structurally resemble some components of human breast milk oligosaccharides, which are extremely complex and change throughout the day. So they are structurally closest to human milk oligosaccharides and are the best immunomodulatory prebiotics that you can have because of what they do in human breast milk.
As opposed to fructooligosaccharides (FOS), which are one single structure, galactooligosaccharides are a mixture of varying oligosaccharides, of varying lengths, and also chemical structures. This chemical structure that they have depends on the origin of the enzyme, so from which bacterium they are produced.
This is key in their functionality, meaning how they are going to behave when they arrive in your gut and how they are going to interact with not only microbiota because all well-designed prebiotics will support the official components of the microbiota, but this specific prebiotic or certain components of the structure will also interact directly with immune cells. That interaction will depend on the chemical structure and chemical structure depends on the origin of the enzyme.
So most commercial GOS’s come from one strain of bacilli, which is alright as a prebiotic, but a better idea is to take, enzymes from a probiotic such as Bifidobacterium. We have plenty of evidence out there, that these guys are good. We not only selected them for their growth but the benefits that those bacteria have early on in life and their interaction with the immune system. I also want to add that this form of GOS is not the same as the ones in soya beans (and other legumes), those are structurally very different.
For our products, we have chosen bacteria that are dominant in adults and it gives it a lot more benefits when it comes to the adult population and its interaction with the immune system. So if you’re looking for a good prebiotic go for trans galactooligosaccharides (TOS) or Beta GOS’s. Beta GOS is great for anyone looking to support their lifestyle, improve their gut, and kick their immune system up a notch. More specifically, people who suffer from gastrointestinal disorders such as IBS or ulcerative colitis could benefit from Beta GOS.
The key benefits of Beta GOS
Beta GOS is in my opinion, is the best prebiotic out there. It is the best thing to take if you want to support the probiotics that are already inside of your body and know how to deal with you and your lifestyle and environment. It gives your microbiota a bit of a kick because it gives the ability to get those good guys to thrive and flourish in your environment. It improves diversity, which we all know is very important when it comes to microbiota.
In addition to that, certain components of those beta galactooligosaccharides will directly interact with the receptors in the immune cells down the gastrointestinal lining. So it gives an additional benefit, which nearly all other prebiotics cannot do because prebiotics are mainly there to feed the microbiota. Beta galactooligosaccharide has the additional benefit of interacting with the immune cells. Their main job is to support our bifidobacteria.
How are the gut and the brain connected?
The gut and brain are connected through the vagus nerve and the gut produces a lot of compounds including neurotransmitters that are then transported via the blood-brain barrier and interact with the brain. All microbiota in the gut will produce something that can interact, not just with the brain, but with every organ in the body, mainly through the interaction with the immune system.
The microbiota produces a lot of compounds that are beneficial and in this case, the ones that we have the most knowledge about are bifidobacteria and lactobacillus. I firmly believe when it comes to giving advice or practical tips that people can use, we should stay within the field where we have the most evidence and knowledge. So these guys are known to produce a variety of different compounds, including neurotransmitters, they influence hormones, etc. And that is how they are connected to the brain and the endocrine function, which is extremely important within the human body.
What is Gut Health?
Gut health to a lot of people is all about microbiota but gut health to me is about things like digestion, absorption, absence of illness, etc. The key to achieving gut health is two entities. One is microbiota and one is intestinal barrier function. So good gut health depends on this intact gastrointestinal barrier and the fine-tuned communication between the microbiota and the immune system. The mechanical barrier that is between the human and its outside environment is crucial for literally everything that's going on in the body. If this barrier is intact and healthy, then it almost does not matter what goes on outside. But when the barrier is not doing so well, that's when the problems start within the gut.
This is important because of the low-grade inflammation that underpins everything that can go wrong in our body from the wrinkles on our skin to Alzheimer's. The only things that are excluded are infections and genetic disorders. So this buildup of chronic low-grade inflammation comes from the environment which includes our lifestyle and diet. The microbiota drives the amount of inflammatory compounds that enter our body. And this gastrointestinal barrier is there to either prevent or let the entry of those compounds.
The low-grade inflammation is a natural process that builds up in our body because that's what is causing aging. And eventually, when we have too much of this low grade inflammation, which we cannot avoid, we’re human, we have an expiration date, it starts to accumulate and gets to the point where we can no longer tolerate it. This is where we start to notice the effects of aging. Our inflammation, barrier, and tolerance are all very important. If we can tolerate a lot, we can stay “younger” (healthier for longer) and if we cannot tolerate a lot, we will get sick very quickly.
So knowing that the microbiota is influential when it comes to the interaction with the immune system, keeping this barrier intact, and the production of a variety of compounds that can help prevent this inflammation build-up, we have decided to focus on a specific strain of bifidobacteria. We've decided to extract those compounds, they are exopolysaccharides, so they are types of sugars that these bacteria produce. They have a specific function because they block the receptors down the gut lining and by doing that they reduce the amount of inflammatory compounds that enter the body. In a way, they are fooling the immune system to think that everything is fine and it does not need to work too hard. This creates more balance in the body.
The hormone connection
Since we knew that this strain reduces inflammation, we also hypothesised that it was going to have a systemic effect on the number of inflammatory compounds including hormones, specifically in females. For example, cortisol a stress hormone, increases inflammation in the body so cortisol is one of the hormones affected.
Another interesting thing is when females go through perimenopause and enter menopause, what happens is sex hormones (mainly estrogen and progesterone) drop. At this same time in the female body, we become more prone to inflammatory conditions. Then what happens is the barrier becomes more porous and more inflammatory compounds are let through. It seems like the sex hormones in the female body regulate the amount of inflammatory compounds that enter the female body.
So taking all of this into consideration, we've decided to test this specific product in a female population ages 40-55. We are looking to see the effect on well-known inflammatory markers such as cytokines, C reactive protein, cortisol, sex hormones, human growth hormone, and DHEA. We hypothesised that we can kind of block those receptors and therefore reduce the amount of inflammatory compounds that are coming from the diet and lifestyle. We also hypothesised that we should be able to reduce cortisol in the blood and saliva and increase the sex hormones that would naturally drop at this age. This is exactly what happened in this study. We have seen a significant effect over the three-month period that we have been testing. We have also found a positive effect even four weeks after stopping which is great because for a lot of these compounds, once you start taking them you usually quickly go back to where you started. I think one of the reasons for that is that we are directly interacting with the immune system so there is more of a lasting benefit within the body.
Why is there a benefit from this strain?
We are born and then we start our descent towards death. And how fast we start moving towards death depends on how much low-grade inflammation we accumulate. This has a direct impact on our immune system in addition to our microbiota. So if you have something that can give your immune system a bit of a break, that effect, in theory, would help you perform better. It gives your immune system a bit of a break from daily dealing with all those inflammatory compounds. And so the immune system can therefore perform a little bit better after a given period.
That's an amazing idea, it is almost like there is a buildup of this chronic inflammation, and then the post-biotic manages to clear some of the inflammation away, allowing the immune system to function more optimally, resulting in an enduring benefit. -Kriben Govender
Bifidobacterium Breve BB091109 (Y Skin) strain selection
We were set on finding a strain of Bifidobacteria because there is a lot of knowledge about them. It's all about healthy ageing so we wanted to work with Bifidobacteria from a healthy older human. A lot of different strains were extracted from the donor that we had chosen. Multiple strains were tested for their ability to produce different exopolysaccharide and their ability to interact with different immune cells and so on. This particular strain, Bifidobacterium breve BB091109, performed the best so it was chosen.
The skin gut connection
The strain that we chose has been shown to slow down the ageing process which means less inflammation. This is connected to the skin because the skin is a mirror of health. Whatever goes on in the body is eventually going to show up on the skin. There is a very strong connection between the gut and the skin. The product we have created is pushing the benefit of a balanced immune system and the reduction of those inflammatory compounds from the gut onto the skin.
One of the issues with selling this product is explaining it to people and the idea is that if you are pushing it from the gut and you want to see healthy skin then you should not be applying too many topical treatments because if you do that you are not allowing the benefits to come out. We have also done studies that have not been published yet where we have looked at the effect on the skin and there has been a significant change over three months.
The future direction of microbiome research
I think we are at a crossroads where a lot of effort, brain power, and money has gone into microbiome research in the last 10 years. We have realised that we have some issues with the microbiota. I do believe that postbiotic concepts or a similar application, is the way forward. I do believe that a lot of labs and companies within this field are starting to think about that concept. I see this as the next generation of products that will be coming on the market.
Artificial Intelligence Technology in microbiome research
I believe this is extremely beneficial because you can deal with a lot of data at once time. We are using artificial intelligence to feed different components, different data, and different chemical structures. I think this will help with personalised nutrition and treatments. When we get enough data from humans and compounds we will be able to design treatments and products that on a personal basis take genetics and environment into account.
Dr Jelena's top gut health tip
The one thing that people should have in life is balance. You have to eat everything and that has to include the bad as well as the good aspects. There is not one thing that is so good for you, other than sleep and drinking (good quality) water, that you should be doing every day. Moderation and variety will result in this balance. If you have this balance in life then your gut will be fine.
In summary, the conversation with Dr. Jelena Vulevic sheds light on the intricate relationship between microbiota, the immune system, and overall health. Dr. Vulevic emphasised the importance of maintaining gut health through a balanced lifestyle, including dietary modifications and the use of prebiotics, probiotics, and postbiotics. Ultimately, achieving gut health requires a holistic approach rooted in moderation, diversity, and balance in lifestyle choices. Make sure to share this with a friend who could benefit from this information!
