B. Brett Finlay studies microbes in our poop. He started with diarrhea-inducing bacteria like Salmonella and E. coli, which inject proteins known as virulence factors into our cells to make us sick. Now he looks at the “good bugs” that live in our intestines: our gut microbiota. These microbes consist of thousands of bacteria and fungi species, and they help us digest our food. They also jumpstart our immune systems by training a kind of white blood cell, called a regulatory T cell, to recognize what good microbes look like.
But we inadvertently wage a war against our good bugs every time we take antibiotics or use antibacterial soap. Finlay worries that we now have a “hygiene hangover,” and children aren’t getting access to the good bugs they need to be healthy.
Finlay, a microbiologist at the University of British Columbia in Vancouver, found that three-month-old Canadian children who were missing four particular gut bacteria were more likely than children who had the bacteria to develop asthma when they were five years old. He and microbiologist Marie-Claire Arrieta further discuss the link between gut microbiota and asthma in their book Let Them Eat Dirt, a guide for young parents about good and bad bugs and how a healthy microbiota is crucial in the early days of a baby’s life.
At the February 2017 American Association for the Advancement of Science meeting in Boston, Finlay announced that his team had found that Ecuadorian children with a fungus, a yeast called Pichia, in their guts were more likely to get asthma than children who did not harbor the fungus. This discovery is the first time a yeast has been linked to asthma. What are these yeast and bacteria doing in our guts? Finlay sat down with SciCom’s Sarah McQuate to digest the latest ideas about our gut microbiota and our health.
How did your lab start looking at asthma?
I got in the asthma world because my wife is a pediatrician. She said that if you treated kids with antibiotics in the first year of life, they got more asthma. So I convinced a grad student to do a simple experiment to just treat mice with antibiotics to see, does that affect mouse asthma? It worked beautifully.
These results are from your 2012 paper showing that antibiotics in baby mice increased their likelihood of getting asthma, but antibiotics didn’t affect adult mice. Your book talks about how antibiotics in human babies are linked with increased risk of asthma as well. Is it because the antibiotics affect the microbiota?
Yeah, antibiotics don’t care. They kill good and bad [bacteria].
In your book, you talk about how Canadian children missing four specific kinds of bacteria were more likely to get asthma later in life.
So when we did the Canadian cohort, we were a bit disappointed [at first] because you didn’t see any gross differences between kids that were at risk for asthma vs. not. But then when we dug deeper, we narrowed down these four bacteria. We call them FLVR, based on the first names of their species names.
So what’s going on here? Are you saying these four bacteria actually prevent asthma?
They seem to be protective. The best experiment we could do to prove they’re causative, not correlative, was to take human kid feces from a three-month-old that we knew actually went on to get asthma and had very low levels of these [bacteria]. We grew these four bugs up, put them in the kid feces, and then put that into germ free mice. If you spike in the four, you then protect against mouse asthma. So that’s as close as we’ve come. We have hints how they’re actually doing it, but we don’t know all the details yet.
"I believe the reason kids puts everything in their mouth is to antigen-sample the world as we know it."
Is there something special about these bacteria?
No. They’re just the four that came out on the big study, so they were pretty nondescript. No one knows very much about them at all. They’re just normal fecal microbes.
Do you know if it has to be all four of them?
Those experiments are under way. Each experiment takes six months to do, so it takes a long time.
Now that you found the FLVR bacteria seem to be important in keeping kids from getting asthma, what’s the next step?
Ultimately the hope would be to determine if young babies are lacking critical microbes, and if they are, add them back to the baby as a probiotic-type agent to prevent asthma risk later in life. We’re working with a company [Commense] to get those four microbes into kids. We have to start with 20-year-olds, and then 15, 10, and 5, to prove they’re safe. So it’s a long haul to put FLVR into kids as a preventative to asthma.
Now you just found that yeast also plays a role in Ecuadorian children getting asthma.
Yes, Pichia yeast marker was the strongest indicator of all, including [the FLVR] bacteria. It came up stronger than the bacterial correlation as a detriment. I can’t speak to the Canadian [study] yet. We should know this summer for that one.
So it’s bad if you have Pichia in your gut.
If you have it, you have a much higher increased risk of getting asthma.
Is Pichia normally in the gut?
We really know very little about their role as normal microbiota.
Can you tell me a little bit about these studies? So somehow you have poop samples from these kids that end up getting asthma when they’re five. How do you do that?
Feces are sampled at three months, one year of age, two, three, four, five, and frozen. Then you take chunks out and analyze them, and you can go back and correlate: this five-year-old really did get asthma.
Oh wow. This is an epic study. In your book, you mention that the gut microbiota trains a baby’s immune system.
That seems to be what happens. We know there’s specific clades of Clostridia [a gut bacterium] that affect regulatory T cells.
OK, so your T cells can interact with gut microbe products to learn what a good bug looks like. But how do they then go, “You’re a Salmonella, you don’t belong here?”
Part of Salmonella is it goes places that most microbiota don’t. That sets off the alarm system.
But I believe strongly the reason kids puts everything in their mouth is to antigen-sample the world as we know it.
So putting everything in your mouth is just giving you a variety of friends?
Yeah: “So this is the world I live in…”
Is there some cause and effect too? Like, “I ate this bug and nothing happened to me, so I’m going to label this a good bug?” or “I ate this bug and now I don’t know what’s wrong!”
Yeah. I would argue it’s both identity and location. Has the immune system seen it or not? Is this getting to a privileged niche [where] bugs aren’t supposed to be?
In your book, you also talk about how the microbiota helps with brain development.
I think they do have a big influence on that. [The microbes] make neurotransmitters and affect the immune system, which affects neural development.
You know, my brain is up here and my gut is down here. I don’t think about them talking very much.
That chapter probably surprised me the most when I wrote it. I was just stunned. I don’t think anyone realized there was such a two-way conversation going on.
In that chapter, you mentioned that the gut microbiota is linked to conditions like stress, depression, and anxiety. How could that work? Do you think the bacteria are purposely doing something to make us sick or are they like, “Oh I’m just living my life here. Sorry these byproducts are making you get sick?”
I really don’t know. I don’t know that triggering anxiety would be beneficial for a gut microbe.
Me neither. So we’ve been talking a lot about correlations or links between the gut microbiota and various health disorders. But I think it’s confusing to compare a likelihood of something happening with personal experience.
Well, they’re correlates. C section: That will give you a 20% higher chance of getting asthma. It doesn’t say you’re going to get asthma. It’s a correlate. This is what epidemiology is all about.
How do we marry personal experience with these findings?
I think the public understands risk factors. If you don’t wear a seat belt, you stand a higher chance of getting killed. It doesn’t mean you will. If you get in an accident, a seat belt will help. And so, if you believe your immune system is useful in life, then you really should believe that you should be trying to help it with these microbes.
Does trying to help my microbes mean I should never take antibiotics?
Of course not! Antibiotics are incredibly effective at controlling life-threatening bacterial infections and have saved millions of lives. They should be used for serious bacterial infections, but not those caused by viruses or fungi—they don't work. For more minor infections, say ear infections, doctors may want to watch and wait a day to see if they are warranted.
So the hygiene hypothesis is basically saying we need to make sure our hygienic measures—clean water, antibiotics, etc.—don’t ruin our chances of being exposed to the good bugs in our environment?
Balance is the key.
You end your book with this rosy view of personalized medicine helping a kid go from being in the womb all the way to first grade. You show a doctor testing the child and her mom’s microbiota to make sure they are healthy during the pregnancy, after birth, and at routine checkups. What do you think it would take to get us to this “near future,” as you call it?
It’s coming fast. I think there will be a whole new generation of "smart" probiotics that can be used to correct microbiota defects. There will also be routine sampling of microbiota in kids and adults, and then tweaking based on probiotics, prebiotics, and nutrition.
____________________
© 2017 Sarah E. McQuate. Sarah’s stories form a community at sarahmcquate.com.
