15-07 Story 1: The Gut Microbiome

 

Synopsis: Scientists are learning that the bacteria living inside us, most notably in the intestines, influence our bodies far more than previously suspected. Our microbiome influences many other organs, particularly the liver, brain, and immune system. Different mixes of these bacteria may account for a great deal of the variability among people, particularly in our weight.

Host: Reed Pence. Guests: Dr. Jack Gilbert, Group Leader, Microbial Ecology, Argonne National Laboratory; Dr. Rob Knight, Professor of Pediatrics and Computer Science & Engineering, University of California, San Diego


 The Gut Microbiome

Reed Pence: We’re all familiar with some of the most important organs of the body. The heart, the lungs, the brain, kidneys, liver and so on. But one of the important components of the body isn’t really you. It’s not your own cells. It’s the millions of bacterial cells living in all of us. Collectively, they’re known as our gut microbiome.

Jack Gilbert: You have about two pounds of bacteria living inside you, and if you think about it, that’s actually the weight of your brain. So, you have a brain’s worth of bacteria living in your gut and on your skin and in your mouth, and in fact pretty much every mucosal surface, every soft surface they can find their way into.

Reed Pence: That’s Dr. Jack Gilbert, Group Leader in Microbial Ecology at Argonne National Laboratory near Chicago.

Jack Gilbert: We’ve intricately evolved, um, our associations with these bacteria over the last 5 million years or 8 million so that we are now heavily dependent upon them not just for digesting our food but also for forming our body. So, our physiology (the makeup of our cells and our organs) and our neurology (the neuro-connections in our brain) only develop properly when they’re challenged by specific types of bacteria during your development.

Rob Knight: Your microbiome weighs about as much as your brain, but it has more cells than your brain does. It has far more connections and far more genes, and by any of those measures the complexity is just immense. And we’re just beginning to scratch the surface of that complexity.

Reed Pence: Dr. Rob Knight is Professor of Pediatrics and Computer Science and Engineering at the University of California San Diego. He says that differences in the bacteria living in us can explain many of the differences in people. Medicine is taking notice.

Rob Knight: Different people respond completely differently even to the same treatments, and we’re starting to think that a lot of these differences the reason for them might be not in our human genome but in our microbiomes. When you think about it we’re all 99.99% identical in terms of our human genomes, but our microbiomes can be only 10% the same between different people.

Jack Gilbert: Every interaction you have with your environment, everything you put in your mouth, every aunt that gives you a kiss, everybody that hugs you, that changes your microbiome. It introduces you to new bacteria. So, if you grew up on a farm surrounded by animals, you’re gonna get a different set of bacteria than growing up in a building. But what’s interesting is that even identical twins growing up in exactly the same house develop different bacterial communities. So, no individual person has exactly the same microbial signature. They’re all unique.

Reed Pence: One of the differences in those bacteria living in our intestines is their efficiency. If someone’s bacteria are good at breaking down food, they’ll get more calories out of the same meal than someone with less efficient bacteria and be much, much more likely to gain weight. And by now we know the mixes of bacteria that correspond with obesity.

Rob Knight: We can tell that there’s differences in different populations. So, for example, we can probably tell whether you’re lean or obese with 90% accuracy looking solely at your microbes, not knowing anything else about you. However, when we do that kind of study, mostly what we have is correlation data. So it’s difficult to get from that to cause and effect, figuring out does the microbiome cause the change, or is the microbiome merely responding to the change.

Reed Pence: However, scientists are beginning to collect some pretty good evidence that cause and effect is what’s going on.

Rob Knight: We have in fact seen that in some pairs of identical twins who have genetically the same but have very different weight. The amazing thing, this is in studies that I have collaborated on with Jeff Gordon’s lab at Washington University in St. Louis, the amazing thing is you can actually take the microbes from those people — so those twins who are very different in their body mass– and you can put those microbes into a germ free mouse that’s been raised with no microbes of its own, basically raised in a bubble with none of its own microbes. And the mouse that gets microbes from the fatter twin itself becomes a lot fatter than the mouse that gets microbes from the lean twin.

Reed Pence: Alteration of the microbiome can occur when we take antibiotics, selectively cleaning out some of the bacteria inside. That’s apparently what happened to Knight after he suffered digestive distress while vacationing in Peru. He needed two rounds of antibiotics to get rid of the intestinal infection and then started losing weight he’d been trying to lose for years.

Rob Knight: So I was doing more or less the same things with diet and exercise that I had been doing previously with an effect on fitness, but no effect on weight loss. But after coming back from Peru, I wound up losing about 60 pounds so fully substantial weight loss.

 Reed Pence: However, there’s no way to predict the result of such a microbial disruption. You could just as easily gain weight as lose it.

Jack Gilbert: It’s entirely possible. I mean you have some circumstantial evidence to support that. But it’s very much more complicated than we would like it to be. Certain types of bacteria seem to cause this response, so you can introduce one bacterium into a person one species and that one species can change the fundamental ecology of the gut and cause an obesity. So taking an antibiotic may or may not induce that kind of response. It’s not like every time you take an antibiotic your gonna put on weight, but if you do take an antibiotic there is a propensity towards changing that microbiome, and if it changes, you can never be 100% sure what the consequences might be.

Rob Knight: The effects of antibiotics over a large population are more that they promote obesity than that they reduce obesity. And you’ve probably heard about the controversy with farm animals being fed antibiotics. What’s going on there is that low doses of antibiotics so far below the therapeutic dose are routinely used in pigs and chickens and other livestock to help them gain weight. So, it’s perhaps not very surprising that they help humans gain weight on average as well. However, if your microbiome is already at a configuration where you’re gaining weight, then it’s possible that destabilizing that microbiome in combination with diet and exercise could have a much larger effect than diet and exercise alone. However, at this stage we don’t have compelling scientific evidence on a large population to make any clinical recommendations. Although that’s exactly the direction we would like to go in in the future.

Reed pence: Gilbert says the efficiency of your gut bacteria are far from the only way they can affect your weight. Scientists are finding that the microbiome also influences other organs. For example, the liver.

Jack Gilbert: Certain bacteria in the gut appear to cause localized inflammation in your intestine and this leads to one of two problems. One: they release lots of chemicals, which get into our bloodstream (we call them metabolites,) they get into our bloodstream and they interact with the cells in your liver and make your liver function in different ways. Now your liver controls how much fat you put on. It doesn’t matter if you eat 2000 calories or 5000 calories, if your liver doesn’t want you to put on weight, you won’t put on weight. And some of these chemicals can trick the liver into thinking it needs to put on more weight. So even if you’re eating, um, you know, the same as somebody else eating apples and pears, if you tricked your liver into putting on more weight with that same food stuff, it would, and some of these bacteria do that.

Reed Pence: That could be why studies are showing antibiotics can be much more disruptive to the body than we previously suspected. New research suggests that antibiotics very early in life may predispose children to become obese, presumably by changing the composition of the bacteria living inside.

Jack Gilbert: We treated mice with penicillin as pups, and it disrupted their microbial development. So, the microbiome they got led to an obese-causing phenotype. So, these bacteria made the mice obese. Using the same mechanisms we just described, but using the mechanisms of controlling the hormones in the gut, and the liver– make the liver make more fat tissue and controlling appetite in the brain. You know if you take those antibiotics it could have a significant effect. But maybe even effect neurological development. So if you kill off certain types of bacteria, it could change the way your brain develops. This could lead to autism, this could lead to neurological misdevelopment, and change people’s personalities and behaviors in ways were only just starting to understand.

Reed Pence: That’s right. The bacteria living in your gut influence the brain. They send signals to the brain that change our behavior… starting with our diets.

Jack Gilbert: They send nerve impulses into your brain, which actually interestingly we believe change the foods you crave. And they can change your food cravings in general. They can make you have a larger appetite, so you actually start eating more, and you get this positive feedback mechanism. They control your liver making your liver put on more weight, and they control your brain making your brain want to eat more. By doing this, they create this perfect environment for themselves. But some of the bacteria appear to actually control exactly what you want to eat. So they may be able to control “Oh I crave fatty foods,” or “I crave salty foods.” And they appear to trigger those cravings based on the exact ecosystem they want to see inside you, the ecosystem that will be best for them.

Reed Pence: And the brain, in turn, looks for bacteria that it prefers. The entire body has an ongoing give-and-take with your bacteria. We couldn’t live without them.

 Jack Gilbert: Bacteria in your gut actually interact with your immune system. I mean your immune system is there for a few reasons. One, it actually attracts a microbiome. It attracts certain bacteria and it captures them, creating environments which they like living in, and it recruits those bacteria to defend the body against bad bacteria, pathogens and viruses and funguses. We need those bacteria in there. Our body actually recruits them. So, that interaction with our immune system actually leads to signals being sent into our brain, which releases chemicals into our brain and changes the way our brain develops.

Reed Pence: Scientists have grown germ-free mice, preventing them from forming a gut microbiome, and found that their brains and bodies don’t develop correctly.

Jack Gilbert: They have, um, missing connections in the brain, and some of its organs are also very misshapen and under-developed. We think this is a precedent for some of the neurological conditions we see in our modern day society that’s becoming more prevalent like autism and Alzheimer’s, like Parkinson’s Disease. These central nervous system conditions appear to be predicated or developed from the wrong kinds of bacterial co-associations going on inside our bodies. Were missing certain microbes in our body, which lead to proper development. So, in some individuals, this is causing neurological failure or developmental problems, and leading to these conditions being more prevalent in our society.

Reed Pence: All of this has scientists thinking about how our environment has changed. For example it might increase the incidence of diseases such as autism and Alzheimer’s disease. It might be one more result of the Hygiene Hypothesis: that our environment is “too clean” to expose people to the natural germs and bacteria we need to be healthy. Gilbert has sampled the bacteria in many home and office environments.

Jack Gilbert: The majority of the bacteria I’d be able to capture in that environment would be from your skin. We’ve known this for a very long time, but we’re now starting to understand what this could mean to human health. If your only source of bacteria when you’re growing up, when you’re developing as a human being, are skin bacteria, you’re missing the myriad of literally hundreds to thousands of other species which you would normally be exposed to if you were living say a hunter-gatherer lifestyle. Obviously we can’t make everybody in the world become a hunter-gatherer. That might be awesome, but it’s not gonna happen. But what we could do is make those homes, make those offices more microbiologically diverse, more appropriate to the development of our body.

Reed Pence: In the future, scientists hope to figure out what bacteria need to be added back into our environments or introduced to people to help them stay healthy. Or it may require removing some factors. For example, scientists have learned that artificial sweeteners in diet soda change the microbiome in a way that tilts toward obesity. But it may take only the addition of a few bacteria to our bodies to cut the risk of many chronic diseases. Researchers have already found a few of them.

Jack Gilbert: We now know that if we add clostridia back into our mouse model in fact into even infant children with food allergies we can alleviate those food allergies. Certain species of clostridia bacteria are there to simulate the immune system to act in an appropriate way to things like peanuts. So it reduces the likelihood that you’ll have an allergic response to peanuts. But I don’t necessarily know if I want to be in a world where we just constantly pump children full of probiotics in order to try to solve the problem, which has arisen from a fundamental change in our lifestyle.

Reed Pence: Gilbert would prefer changing our environment to make a healthy microbiome part of the natural process of living. One thing he’s done, for example, is to get a dog. Having a dog in the home has been shown to rapidly increase the movement of bacteria and increase their diversity. If we find more simple ways to develop a healthy microbiome, we may not have to give people pills to do it, and so have a lasting impact on human health.

You can find out more information on a project exploring what’s in your own microbiome at americangut.org. You can find out more about all of our guests on our website: Radiohealthjournal.net. I’m Reed Pence.

 

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