Microbes on a diet
Sara DiRienzi explains to Chris Smith what happens when mice are fed on a diet enriched with linoleic acid, an essential fatty acid that we eat an awful lot of these days…
Sara - So I got to thinking about what we do in our daily life and that's that we eat a lot of food, but what we eat from day to day frequently changes quite a bit. And that food that we consume, this is exactly what our microbes get to feed off of. So if we're changing everyday with they get to see, you would think that we would be changing what microbes live in our intestine every day. But that's not true. Over time, we actually see that our gut microbiome is reasonably stable and so the big broader question is how do we maintain a stable gut microbiome? Either the gut microbes themselves have mechanisms in order to deal with a rapidly changing diet or there's the host gut environment is somehow buffering that direct interface between the diet and the gut microbe, and changing how that interaction occurs.
Chris - Indeed, microbiologists often reassure people, even lonely people, that thanks to your microbiome you never dine alone! But the point is that this is really hard to test isn't it, because the microbiome is very diverse, diets are very diverse, people are very diverse? So how have you sought to control this and try and turn those enormous numbers of variables into something tractable?
Sara - Well, I also just want to bring up that this question is actually even more complicated when you're really talking about the diet that we eat. This is really a question for the small intestine and not a question of the large intestine. Less than 10 percent, sometimes even only 1 percent, ever really reaches the large intestine.
Chris - Okay. So just talk us through the experiment then and essentially what you did.
Sara - So if you follow with the very simple hypothesis that when we consume dietary fat it's broken down into its individual fatty acids, and those individual fatty acids are what interact with gut microbes. So what we can do is to simply take those individual fatty acids and directly put them on gut microbes that are found in the small intestine - these fatty acids. So, for instance, like linooleic acid directly inhibits gut microbes that are found in the small intestine.
Chris - That's rather strange isn't it because linoleic acid is one of the essential fatty acids? We can't make that in the body through our own metabolism, we're absolutely dependent on our diet as a source of that, so it seems rather counterintuitive that something were obliged to eat is going to poison our microbiome?
Sara - Exactly. Moreover linoleic acid is also the fatty acid that we consume the most of. It's highly abundant in vegetables and nuts so it's found in all of your vegetable oils. You know these are food you eat every single day.
Chris - And that being the case then if it's that toxic we shouldn't have any of these microbes left in our microbiome should we? We should have driven them all out of existence, so something's going on?
Sara - Exactly. So then we get to; well let's see what actually occurs in the small intestine. So to do this what we set up was a long term diet study. In this study we designed diets that were very carefully controlled and just differed in their percentage of fat versus carbohydrate. And the specific fat that we use in this diet was soybean oil rich in the linoleoic acid. So by putting put mice on these different diets we can see what happens to their gut microbiome. So when we do that, really kind of surprisingly, is you don't actually see very big changes at all, which is not what you would expect based off of what we see that happens in a test tube.
Chris - One of the perils of extrapolating to the in vivro situation; what goes on in vitro isn't it this? It suggests then that something must be endowing the microbiome when it's in vivo with more resiliency; that there's some protecting factor or something else is going on?
Sara - Yeah. So we also took this study a step further. We used a compound called propidium monoazide. And what it does is that it allows us to identify microbes that have been affected by the inhibitory effects of linoleic acid. So what we see is that those gut microbes that were inhibited in the test tube, they're not showing that inhibition in the gut. In fact, they're actually doing better than some other got microbes. So, in fact, what we're seeing is that some of these gut microbes are not directly seeing linoleic acid in the gut the way that they directly see them in a test tube.
Chris - So that would suggest then that something is getting in the way of the access of that chemical into those microbes or, the microbes themselves are doing something different when they're in situ in the gut where they're supposed to be?
Sara - Absolutely.
Chris - But you don't know what, or do you?
Sara - No. Well we have some hypotheses. These gut microbes that we're talking about, they are known to live deep within the mucus. And so it might be that these specific microbes we're looking at have gone and just hidden within this mucus layer and so they essentially have a protective shield.
Chris - And can you get at that?
Sara - Yes. So we have some ways to move forward, and one of our approaches that we can use is a technique called experimental evolution. And what this technique allows us to do is to look at the genetic changes that gut microbes acquire as they're routinely exposed to a stressor. So in this case our linoleic acid is the stressor. When we do this experiment in a test tube, we see that gut microbes change the way that they metabolise fatty acids and they change their membranes. So then we can ask are the gut microbes that have survived this exposure, do they have those same changes in fatty acid metabolism and in their memory? And the answer is no they don't. And so this, again, is highlighting that these got microbes are not directly interacting with linoleic acid.