Tracking the Daily Rhythms of the Microbiome

IRA FLATOW: This is “Science Friday.” I’m Ira Flatow. Almost every week, there is some discovery about the microbiome. What do you imagine a day in the life of one of your gut bacteria might look like?

Dear, diary, today, woke up to the sound of the stomach grumble alarm. Made it on time to roll call with the other actinobacteria. Had to battle a few hostile Clostridium to make it to my spot.

Had a hard time meeting my metabolite quota for the day. Must have been that late high fat burger bomb we received yesterday. There’s whispers of a possible penicillin push. We’ll wait and see. Well, time to hit the sack– the intestinal sac, that is.

Of course, we have no idea what your microbiome might actually be thinking. But one researcher did keep daily diary of his microbiome. He tracked his own microbes for an entire year, sampling them every day. He’s here to tell us what he learned from tracking his own bacteria. Lawrence David, assistant professor of Molecular Genetics and Microbiology at Duke University in Durham, North Carolina, welcome to “Science Friday.”

LAWRENCE DAVID: Hello.

IRA FLATOW: So tell us, you actually took samples every day of your microbiome and kept track of the bacteria in them?

LAWRENCE DAVID: That’s right.

IRA FLATOW: And how– Wow. I’m speechless. And you did it from your mouth and your gut, right, two different places?

LAWRENCE DAVID: Yes, those are two of the easier places to get to.

IRA FLATOW: And what was the hardest part of that process?

LAWRENCE DAVID: Well, there were at least two. One was, as you might expect, sampling your stool every day for a year, it took a little while for that to start becoming a normal habit and not feel too gross. And the second was– that was I’d say even harder– was one of the things we were interested in– and I’ll say I was doing this actually with my graduate advisor at the time– what we wanted to do is figure out, not just how bacteria were changing over time, but figure out what parts of our daily lives might be affecting those dynamics.

And so what we spent a lot of time and effort in doing was tracking how we were also just living our lives and where we were going, what we were eating, how we were feeling, and seeing if we could link that to the bacteria. But all of that tracking took a lot of time, actually a lot more time than I had initially expected. And so I’d say that was one of the harder parts.

IRA FLATOW: Were you able to find a correlation between what you were doing– traveling, eating, going abroad? I understand you traveled out of the country. Did you notice changes?

LAWRENCE DAVID: Oh, sure, yeah. I saw changes in just the gross abundances of different kinds of bacteria that were in my gut when I traveled abroad. But what was really interesting was that initially I thought, well, I’d be going abroad and exposed to all kinds of new bacteria and I’d end up with new kinds of microbes inside my gut. That wasn’t really the case.

And instead, what it turned out happened was about– if you look at the bacteria that I sampled in my gut while I was abroad, about 90% of them were already there before I left. And vice versa, most of the bacteria that I had with me before I left managed to hang around while I was overseas.

IRA FLATOW: So you didn’t really get any new ones coming in? Just the size of the ones inside of you just shrank and expanded?

LAWRENCE DAVID: That’s exactly right. And that, to me, was one of the most interesting observations in this study, was that it looks like it’s really hard to pick up new bacteria, that the ones that are inside of you at any given time really are going to persist for a while. And getting new ones in there, I think, is not easy.

IRA FLATOW: Did you try to eat any probiotics, either in pill form or whatever, to see if you could change the bacteria in there?

LAWRENCE DAVID: Yes. So when I looked back over the course of the year, one of the things that I tried to do, or a goal of this study, was not to change my regular lifestyle and just see what kind of normal variation or normal day-to-day life did to the microbiome. So when I looked back, it turned out that occasionally I’d eat yogurt. And you could see those bacteria in stool samples that I collected, maybe the day after I ate them. But they didn’t really hang around actually much longer after that.

IRA FLATOW: So that was very surprising to you, I imagine.

LAWRENCE DAVID: Oh, yeah, of course. Although looking back, I think others had noticed that too when looking at how long bacteria that are found in fermented foods or dairy products stay in the gut.

IRA FLATOW: You had a collaborator who also collected his microbiome. And he got sick during the project. Did you see a pattern for why he got sick?

LAWRENCE DAVID: Yeah, so that was, I’d say, one of the other really surprising and notable observations in our study. What happened was, in this subject, he got Salmonella. And what ended up happening is that, in that week that he was ill, about half the bacteria that were present in his intestine– it looked like in a pretty stable way for months before that illness– about half those bacteria just sort of dropped out and fell to about the detection limit for our methods for identifying bacteria. And they stayed down for the remaining, I’d say, three months that we were observing him. So that to me spoke to potentially things like illness or infection potentially having a really profound impact on bacteria in the gut.

IRA FLATOW: I want to bring on another guest, because our gut bacteria, as we’re learning, has as an order– our microbes have a circadian rhythm. Our body’s clock that keeps things internally on schedule has that rhythm. But it turns out, the microbiome has its own circadian rhythm too.

In research published this week in the journal Cell, scientists looked at this clock inside of our gut. And here to tell us why that is important and what they found is Eran Elinav. He’s an author on that paper. He’s also a senior researcher at the Department of Immunology at the Weizmann Institute of Science in Rehovot, Israel. Welcome to “Science Friday.”

ERAN ELINAV: Hi there.

IRA FLATOW: Dr. Elinav, you had a study out a few years ago that saw our circadian rhythm can affect microbiomes. And this recent paper was a mouse study. And you saw that it’s a two-way street, that the microbiome has its own clock.

ERAN ELINAV: Absolutely. The scientific community has realized in the last few years that we have millions of different clocks in our body. Actually, we have a clock in every one of our cells in our body. And in a very interesting and fascinating way, they are coordinated in their functions.

And since we regard our guts microbes as an integral part of our body, we wanted to test whether they too have a circadian activity. So we measured them at different times of the day using many different techniques. And we were amazed to find that our gut microbes in many different aspects behave differently at different times of the day.

IRA FLATOW: Do they sync up with other clocks in our body? Or are they on their own clock?

ERAN ELINAV: Yeah, so they are actually very well coordinated with our own, our human, or mouse host circadian clocks. And in fact, what we were amazed to see that the two clocks behave like, if you may, like a tango, in which they greatly influence one another. For example, if we disrupt the microbes, our host clock goes crazy, and hundreds of different genes either lose or gain a circadian activity that was not present before.

IRA FLATOW: Were you surprised by this?

ERAN ELINAV: We were highly surprised. The microbiome field is a very young field and is gathering information that points to the possibility that, in fact, our human body, or our human machine is a compound machine that is composed of the host part and the microbial part. But this behavior, which is so well coordinated, just gave us a classical example that basically confirms these observations. So if we disturb one of the partners, the other partner is very dramatically affected.

IRA FLATOW: Yeah, I wanted to ask about that. If it loses the synchronization, if the microbiome starts losing that synchronization, what happens to the body?

ERAN ELINAV: So in this study, we’ve tested this effect in two different body sites. The first one was the gastrointestinal tract itself, which is located just where the microbes were. And there, we saw that if we disrupted microbes– for example, by administrating a wide-spectrum antibiotics– immediately, the normal circadian rhythm of the host gastrointestinal cell was completely disrupted and changes its behavior to a very new behavior.

But what was even more fascinating for us occurred when we tested the liver, which is located, if you may, miles away from where the gut microbes live. And when we tested the liver circadian rhythmicity, we said that it too was greatly affected by the clock activity of the microbes. So if we disrupted the gut microbes by killing them by antibiotics or by even performing a study in mice that do not have any gut microbes of themselves– these are sterile, germ-free mice– the liver circadian rhythmicity was very dramatically changing as well.

IRA FLATOW: And so do we disrupt them? Do we unknowingly in our daily lives by what we do and what we eat and things like that, do we disrupt the cycle of our microbiome and possibly cause ill effects on our bodies?

ERAN ELINAV: Absolutely. So an integral part of modern life involves many unintentional interventions that potentially could disturb the normal rhythmicity of our microbes. In our studies, both in mice and in humans, we induced a severe state of, if you may, jet lag or a state that imitates shift work, in which the day and night cycles are disrupted over a long period of time. And one of the first and most pronounced changes that we saw was a change in this normal microbial rhythmic activity.

And this resulted in a change of the microbe towards a configuration that predispose both the mice or the humans to develop obesity, diabetes, and their complications. And actually, if you look in the medical literature– and now, I’m talking as a physician– for the past 50 or 70 years, there has been a lot of literature pointing towards a possible connection between chronic disruption of normal sleep-wake cycles, such as the shift workers, and a propensity to develop obesity and diabetes. And our study suggests that at least one potential important, previously unknown explanation for this association lies in the normal cyclic behavior of our microbes, which is so easily disturbed when we disrupt our daily routines.

IRA FLATOW: I’m Ira Flatow. And this is “Science Friday” from PRI, Public Radio International, talking with Dr. Eran Elinav and Dr. Lawrence David about our microbiome. Dr. David, did you notice in collecting your own samples at different times of day different microbiome?

LAWRENCE DAVID: No, I didn’t. And one of the really interesting things that really impresses me about Dr. Elinav’s work is that, it didn’t really occur to us to actually look at changes within a single day. We were taking advantage of just sort of natural human circadian rhythms. And myself and my collaborator didn’t really tend to produce stool more than once a day. And so I think that’s the real power and really exciting thing about, again, what Dr. Elinav is doing, is showing that within a single day, we see these kinds of dynamics.

IRA FLATOW: Yeah. What’s also interesting. There doesn’t seem to be a day that goes by or a week that goes by without a continuing stream of new research about the microbiome. There was even research out this week about in mice that got microbiome affecting possibly Parkinson’s disease. Are you as amazed as I am as I read about all these, Dr. Elinav, about all these new things we’re learning?

ERAN ELINAV: Yeah, we are quite amazed and fascinated but the amount of new data. We need to remember that we’re talking about a field that was just reborn just eight or nine years ago following the technological breakthroughs that were part of the Human Genome Project. So this is a very young field. But in a very short period of time, we discovered that we have a second genome, which is 150-fold larger than our human genome, and lives right with us throughout our life. So, of course, it is not surprising that this affects our physiology or our tendency to develop disease in very fascinating new ways that we haven’t imagined before.

IRA FLATOW: Dr. David, where do you go now? Are you going to continue with your diary collecting? Or do you modify it? Or what would you do next?

LAWRENCE DAVID: Oh, no, not at all. And in fact, I totally stopped doing that kind of diary collection. One of the other impetuses for this project was to get a sense for– engineers call this, eating your own dog food, as meaning as someone designing these studies, what could we ask subjects and participants to do reasonably that wouldn’t be too onerous? And one of the things that I took away from this is that it’s a lot of work to track a lot of different variables in one’s life and try connect them to the microbiome.

So what we’ve done since then is focus in on specific components of daily life. And one of the things that we looked at in the past are things like just changing diet. And speaking to your earlier question, we have seen that a big change in diet within a single day can change the microbiome. And something else that we’ve been looking at now are probiotics and trying to figure out, well, how could we design them better, so that they do persist longer in the gut?

IRA FLATOW: And what does that microbiome like to eat? What makes it healthy?

LAWRENCE DAVID: It eats both some of the different kinds of sugars that come in from the plant matter that we eat, all the– but also actually, we feed it as well. And I think that Dr. Elinav’s work speaks to this too, how our bodies actually also secrete different kinds of sugars that feed the bacteria inside of us.

IRA FLATOW: So what kind of diet, Dr. Elinav, should we eat to make our microbiome healthy?

ERAN ELINAV: Well it’s a billion dollar question. And actually, in one of our other works performed in over 1,000 human individuals, we actually discovered that there is not one good or bad diet for all individuals. And actually, diet, just like our microbiome, is very individualized. And we actually offered some new ways to collect a lot of data from each individual and to design diets that are personally good for that individual.

IRA FLATOW: This is great stuff. We have a lot more to talk about in the future. I want to thank you both for taking time to be with us today. Dr. Eran Elinav, senior researcher at the Department of Immunology at the Weizmann Institute of Science in Rehovot, Israel, Lawrence David, assistant professor of Molecular Genetics and Microbiology at Duke University, thank you both for taking time to be with us today.

One last thing before we go– calling all teachers, applications for our 2017 Science Friday Educator Collaborative, well, it’s now alive. We’ll work with you to develop free classroom resources for educators nationwide. You can apply now at sciencefriday.com/educator. That’s sciencefriday.com/educator. 2017 Science Friday Educator Collaborative is now alive.

BJ Leiderman composed our theme music. And our thanks as always to our production partners at the studios of the City University of New York. Have a great weekend. We’ll see you next week. I’m Ira Flatow in New York.

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