How the microbiome affects blood pressure

Inside each of us is a thriving family of microbes that outnumber our own 37 trillion human cells at least twofold. Together they weigh in at over a kilo, and some scientists now regard this microbiome, as it’s known, as an organ in its own right, and also one of our greatest medical oversights, dismissed for decades as mere colonising microbes. But in recent years we’ve begun to realise that the suite of thousands of biochemicals released by these bacteria and fungi, and the metabolic knives and forks they bring to our digestive systems, are crucial to health and disease, determining even our blood pressure, as the University of Toledo’s Bina Joe explains to Chris Smith…

Bina - We are working on the microbiome and we are looking at how this microbiome influences blood pressure hypertension, which is the number one risk factor for cardiovascular diseases. And our lab was the first to discover that the tiny bugs that live in our guts actually tweak our blood pressure.

Chris - What's the evidence for that association before we think about how they might be doing that, what's the pure evidence that they are even doing that?

Bina - I will go back to my first publication where we did this experiment. We took a rat with normal blood pressure and asked, if its microbiome is perfect, then can we then take its slurry of bugs in its gut and add it to animals that have high blood pressure. But to our astonishment, what happened was it did not lower blood pressure, but it further increased its hypertension, which was the first piece of evidence that these bugs are doing something to the blood pressure of these animals.

Chris - Is there wider evidence that this is not just a laboratory phenomenon though If we look in humans, can we see signs that what lives in us may be influencing our blood pressure?

Bina - Absolutely. So following our animal experiments, human geneticists started exploring this idea and find associations of gut microbiota, which is the bugs in our bodies with people's blood pressures. So there are considerable studies now showing this as conclusive association in humans. The point association is it's difficult to prove causation, and therefore we go back to the animals and then show that when there are animals which don't have any bugs in them and then you introduce germs into them, blood pressure increased. So that was the causative evidence that we went after for what is the next mechanisms question, right?

Chris - Indeed. So if something causes something to happen, there must be a plausible biochemical mechanisms. So what do you think they might be doing that would manipulate the blood pressure in a host animal?

Bina - That's the million dollar question. I wish I could answer that. These microbes generate thousands of biochemicals and they secrete them into our bodies. So we are looking into which one of these chemicals that they make affect our blood pressure. We don't have answers yet. We have a few indications of some metabolites, but not all of them. And that's where the research space is currently.

Chris - Over the years when we've learned then that diet has a really important role to play in cardiovascular disease. Mm-Hmm. <Affirmative>, do you think a contribution of our diet is that the microbes digest our dinner and they make biomolecules, which then in turn affect our disease risk?

Bina - Absolutely. That was how we started this research. Think of salt, it's the number one dietary factor that increases blood pressure and salt is used for ages to make pickles. So salt kills bacteria. Think of consuming salt and that rearranging your, the population of the bugs in your body. That's exactly what it does and that's where it got fascinating for beyond diet. What else are we eating to kill bacteria? Classic example, antibiotics. Are we consuming antibiotics and changing our physiology? Yes we do. In our animal models three different antibiotics that we tried actually raised blood pressure in our animals and that's alarming before they went and asked, is it all the antibiotics or only some we tried amoxicillin because it's used in children so often and at least in our animal model, amoxicillin was the only one that did not increase blood pressure. So we are saying that might be the safe one, but other antibiotics did raise blood pressure. Then you can expand it to what are the environmental agents? There are so many herbicides we decides that we use, they are to kill plants, but they also kill microbes. So are we exposed to agents that destroy our microbiome? The answer is yes.

Chris - And to what extent might these effects be permanent? Because we use a lot of antibiotics and we almost certainly are demolishing people's microbiomes for a while when we do that. Does that leave holes in the microbiome when it comes back, which are going to set people up to develop some of these conditions, or do they fill in those holes and reacquire the missing microbes again, so antibiotics are a short term curse, but it's only a major problem if you're on them for a long time?

Bina - I referred you to a paper that came out in Nature a few years back where they compared paleo faeces, which is 7,000 year old poop samples and compared the microbiome in that sample to modern day industrialised world with some European countries represented and with underdeveloped nations and developing nations microbiomes of humans. And they found that the ancient microbiome aligned with the underdeveloped and developing nations develop microbiomes better. Which means clearly that the industrialised nation, which there is maximum exposure to all the environmental agents that I was talking about, including antibiotics usage, we have probably changed our microbiome drastically...

Chris - Do you foresee then a time coming where when we assess a patient rather than just give them another anti-hypertensive to try, we will be looking at their microbiome and asking what can I add or what can I subtract microbe-wise - through probably giving different food stuffs to manipulate the microbiome - and that will have as much efficacy as some of the pills we give people?

Bina - Absolutely. Chris, I'm a believer in this for hypertension, we have been focused on genetics for too long to look at genes in our bodies that are different variations of which are associated with human hypertensives. Right? But that's only 30% that can explain the incidence of hypertension. So what is this other 70%? We have been looking at the environment and we bring in microbiome as a new less appreciated in the past discovery piece for, to look at or what I'm trying to say is it's not just treatment with pills. Another thing we have done is we have inserted an antihypertensive gene called ACE II - angiotensin converting enzyme II - to bacteria lactobacilli and gave it as a probiotic to our animals and it's able to lower blood pressure. So there are opportunities for manipulating microbiota and using them as pills if you may want to before you develop hypertension.