E241: What is the connection between the gut and our brain?

We've recorded a series of podcasts on the microbiome and its wide ranging impacts. But boy is this a field that moves rapidly. As soon as you think you've covered much of the territory, along comes some new and exciting findings, and this is the case today. We're going to describe research done by our guest, Dr. Ibrahim Javed. He has done innovative work on links between the gut microbiome and the brain, particularly focused on Alzheimer's disease. Dr. Javed is an Enterprise Fellow and National Health and Medicine Research Council Emerging Leadership Fellow in Clinical and Health Sciences at the University of South Australia.

Interview Transcript

So let's begin, if you wouldn't mind, with an explanation from you about what the gut brain axis is and tell us how it's important.

Yep. Now we see a lot of, a lot of researchers around the globe building on investigations around the gut brain axis. But if we, if we investigate what this gut brain axis actually is, It's kind of like a bi-directional communication between two organs in our body, the gut and the brain. And when we particularly talk about gut, we have our stomach and our different portions of the intestine.

What we're actually interested in is the microbiome and all those small little things living inside the gut. There are around 100 trillion microbes in the gut, which is three times more than the number of cells in our body. So, we are kind of like more microbes than, than human cells. And they communicate with different organs in our body and how they communicate with the brain that we can describe it as a, as a gut brain axis. And then this whole gut brain axis thing was somehow kind of invisible to us. We were just looking at it as a fecal material or waste coming out of our body. But now we see a lot of importance to these gut microbes. They help us in a lot of daily things that we do. They shape our behavior, our response to stress, our immune system, and then how we respond to different medicines, and how we do our daily tasks. So, they have a lot of roles in that. They help us digest food, that's their main obvious function. But now we are more. getting more and more information about them, that how they are integrated with a lot of different things in our body. So, kind of like they are partners in our life.

That's a very, very nice explanation. Can you tell us about the importance of microbial diversity?

Yep. So microbial diversity, we can, we can refer to, to as a composition of all those bacteria, viruses, and fungi to some extent that, that live in, in our body. Digestive track and, and in a lot of other animals as well. And this diversity is very crucial in maintaining the gut health and on overall well-being of, of humans. And, and this microbiome whole thing is like, it is obviously associated with a lot of health benefits and, and how we develop disease, but it's also right from the beginning of life they help us in developing our brains. They help us mature the brain system and the immune system. Obviously, they help us in digesting food.

So, generally, we can actually divide them in two portions. One, we can call them a good gut bacterium. They help us with all these things. And then they are bad gut bacteria, which are kind of like kept within a within a bay. They are kept under control by this good gut bacteria with the help of the rest of our body. And in somehow in some conditions with the age or with the dietary habits or environmental factor or lifestyle, if they overcome and, and they take over the control in the gut, that's where the thing starts going haywire.

When I was growing up, microbes were a bad thing. You didn't want to have microbes. And now, now we hear that there are good microbes and now you're talking about the balance. There are still bad ones, but good ones. And the balance of those two was a really important thing. Let's talk about how bad bacteria find their way to the brain. How do they get access?

So, as we discussed, they are kept within the bay or kept under control by good bacteria and also by other different immune systems in the body. We have different checkpoints, like we have different barriers or three different compartments, the gut and the blood and the brain. And we have barriers that separate out these compartments and these barriers are very tightly controlled, very good health cells tightly integrated with each other and they police that whole things what need to go across and what does not need to go across what we need to stop it within that compartment. If we have adverse environmental factors, or poor dietary habits and these bad gut bacteria overcome, they produce a lot of different molecules to communicate with each other. And they produce a lot of different molecules to take over the good bacteria. And these molecules, they can get across those barriers, and specifically if they can get into the brain (that's what we are researching), they can do a lot of different bad things in the brain. They can do that by hijacking this gut brain axis. And this compartmental thing is one pathway that they can get from gut to the blood and then from the blood to the brain. But there is also a direct highway that connects gut to the brain and that's our enteric nervous system. These are specific nerves or neurons, for example, vagus nerve, they're quite famous. It's a direct link between the gut and brain. This nerve system helps us in a lot of different daily tasks without us even knowing about it, like digestion and heart rate and respiration, and emptying the stomach. And these are kind of like a pathway for bidirectional communication. So, a lot of molecules go up and down across these highways and the bad gut bacteria can actually hijack it and they can put their stuff into this highway and they can send it across the brain.

It's a very, very nice explanation you have of a very complicated process, and I find it absolutely fascinating. So, you've spoken about how bad bacteria can be opportunistic pathogens and can trigger problems or enhance the progression of existing problems. How does all that work?

So, we are investigating bad gut bacteria in connection with dementia and Alzheimer disease. We are specifically working on Pseudomonas aeruginosa and E. coli and they are quite common, like a lot of school kids. They know about these bacteria. They are quite commonly studied in high school microbiology.

So, these bacteria produce some molecules which help to make biofilms around them. They kind of build a castle around them to protect their colonies and for their own survival and they keep surviving then until they get an opportunity to expand their castles and build more biofilms. These molecules are quite similar in terms of their structure and in terms of how they communicate. With some proteins which are not related to bacteria anyhow, they are produced in the brain to do some normal stuff in the brain, but they also aggregate in Alzheimer disease using the same mechanism as the nature that these bacteria use for these proteins to make their biofilms.

Based on this common similarity, if they can somehow see each other, or if those gut bacteria can send those proteins or aggregate of those proteins across the brain through using those highways. They can induce the aggregation of those normal, naive, working, innocent proteins, which we have in our brain that have nothing to do with the bacteria. But if they can be accessed by those bacterial proteins, they go haywire and, and they trigger the onset of the disease, or if there is already going on, that they can actually accelerate that whole process. And this is a concept, actually, we have seen that concept before in prion disease, whereby eating infected food that have those prion particles, they can actually go from gut to the brain, and they can induce the normal prion protein in the brain to start making aggregates in a similar way.

Are there interventions that can stop the pathogenic bacteria from in the gut that might in turn affect the brain?

We should focus more on preventive measures. We can focus on maintaining a good diversity within the gut of having or supporting those good bacteria in that fight and keeping them healthy and alive as we age. Because as we age over the period of life, we keep losing those good bacteria. If we can have all those good things of exercise, balanced sleep, and more importantly, good food and a balanced variety of food. Then we have a lot of different varieties to support that variety of gut bacteria in the gut.

So that's, I think, the most important preventive measure to keep that balance intact. But of course, in the future as a therapeutic intervention, we are moving towards developing microbiome therapies where we can modulate those compositions. If that composition is not in a very good situation, we can actually modulate that by using probiotics and prebiotic dietary factors or some microbial compositions like yogurt and a lot of other foods. We can modulate that to inoculate those bacteria which are missing in the gut and, and try to achieve that balance and, and that balance will accelerate the effectiveness of the medicine which we are taking for any other disease.

The advice we've heard from some of our other guests is to eat a diet rich in fruits and vegetables. You know, consume things, you mentioned yogurt, kefir, kombucha, sauerkraut, and things like that. Sound like they're very good for enhancing the health of the microbiome. Is there anything else beyond that that might be relevant for the brain in particular?

For brain health, there are some antioxidant foods. For example, we have Curcumin, and some senolytic compounds. We cannot call them drugs because they are kind of like a food supplements. They are available in any pharmacy and super stores by a lot of different names. Mostly these are polyphenolic compounds. They are usually available in green tea and in green tea extracts. They are quite well known for their healthy and antioxidant and anti-inflammatory effects. Research around the globe has shown that there are good effects directly on the brain by these polyphenolic compounds. So, these are green tea extracts, quercetin and, and some other galectin compounds.

BIO

Dr Ibrahim Javed is currently an Enterprise Fellow (Senior Lecturer) and NHMRC Emerging Leadership Fellow at the Clinical and Health Sciences, University of South Australia. He is also an adjunct Senior Research Fellow at the Australian Institute for Bioengineering and Nanotechnology (AIBN), The University of Queensland. He completed his doctoral studies at the Monash Institute of Pharmaceutical Sciences in 2020 and postdoctoral research at AIBN, The University of Queensland. He joined the University of South Australia in 2023 where he is now directing the laboratory of Gut-Brain Axis, Aging and Therapeutics. Research in Javed’s lab focuses on the gut-brain axis and its implications for aging and Dementia. His research team is working to unfold the specific role of bad/pathogenic gut bacteria in the aging paradigms and Dementia associated with Alzheimer’s and Parkinson’s diseases. His team has discovered and published the molecular details of how bad bacteria in the gut can trigger a younger onset (aged under 65) and accelerate Dementia and how the brain can develop Dementia when fighting with microbial biofilms in the gut – the infectious etiology of Dementia. With this research trajectory, his vision is to develop a multifaceted therapeutic intervention for aging-associated diseases and Dementia.