Microbes Benefit More Than Just The Gut
IRA FLATOW, HOST:
This is SCIENCE FRIDAY from NPR. I'm Ira Flatow. Now, we know that a thriving colony of bacteria keeps your gut healthy. You might even take probiotics or eat yogurt to keep it that way. But bacteria just don't give you an intestinal boost. They make keep things in check all over and inside your body, including your nose, because a new study suggests that people with chronic sinus problems have a less diverse garden of microbes in their nose than healthy people. And listen to this: Mice who sniffed a dose of friendly lactobacillus bugs up their nose seem to have healthier sinuses than mice who didn't.
The research appears in the journal Science Translational Medicine. So instead of the steroid sprays, the decongestants, the saline rinses, might a bacterial spray be a better option for keeping the sinuses congestion-free? Joining me now to talk about this is Susan Lynch, associate professor of medicine at UC San Francisco. She's also director of the Colitis and Chron's Disease Microbiome Research Core there. She joins us today from KQED. Welcome to SCIENCE FRIDAY, Dr. Lynch.
SUSAN LYNCH: Thank you so much. My pleasure.
FLATOW: You know, we talk a lot about the germs in our bodies and how many there are spread all over the place. But usually they're in our guts that we're talking about it. We haven't talked much about what's going on in our noses. What is happening up there?
LYNCH: That's true, and I think the field of human microbiome research has really, in the last four, five years, really exploded upon the scene and shown us that many niches in the human body are colonized by bacteria, be it our skin, our mucosal surfaces. These are the softer linings that line the nares, the sinuses, the gastrointestinal, the airways and the urogenital tract. And what we're beginning to see is that these linings of the human body are actually home to a diversity of microbes.
And from much of the studies that have come from the gastrointestinal tract, which has been going on a little longer, we've seen certain hallmarks that are associated with health and disease. We know, for example, that when patients have chronic inflammatory disease, one of the characteristics is this loss of diversity. And sinusitis is quite a significant health care issue. And really, to date, much of the microbial studies that have been performed have largely been based on culturing and bacteria, so trying to grow them on agar plates.
LYNCH: But we know that that shows us maybe a very tiny fraction of the bacteria that are truly there. So instead, we wanted to use these culture-independent approaches that have been developed over the last few years to identify the conglomerate of organisms that are present and the true diversity of bacteria that are present and determine whether that's different in states of health and disease, specifically in the sinus niche, because it's an area that really has not had a lot of studies performed in it before this.
FLATOW: And so you've found that people who had less sinus problems had bigger diversity in their...
LYNCH: Yeah, that's true. Yep, exactly. So we applied these methods, which you can think of as kind of scanning for molecular bar codes for bacteria, and each barcode will tell you which bacterium it came from. So you can get a profile of what types of bacteria are present in a given sample. And you also get to find out how much of that type of bacteria is there. So we get kind of like a fingerprint of who's present from a bacterial standpoint in the samples.
And we simply took surgical samples of the sinus lining from patients with chronic sinusitis and healthy individuals who didn't have sinus disease but were in for surgery for different indications. And we simply compared those samples and asked the question, what's different between patients with chronic sinusitis and healthy individuals? And we show that the sinusitis patients had this incredible collapse of the microbial community in their sinus cavity.
And they were characterized by having kind of an outgrowth or an enrichment of this one bacterium called corynebacterium tuberculostearicum - it's quite a mouthful - and we know very little about it. And as it turns out, this organism typically lives on the skin and really doesn't do anything harmful there. But in the context of a loss of the microbial diversity and this organism there in very high numbers, this is what characterized the patients.
So we moved on to look at this in mice and to really see if something that we consider to be not very harmful in one context could, under this depletion of the microbiome, cause hallmarks of disease. And that's indeed what we found in our murine studies, in our mouse studies.
FLATOW: So if you had a healthy population to offset the bad bacteria, that kept you feeling better and not...
LYNCH: Exactly. And the nice thing with the study was that we got to find out what was characteristic of healthy sinus cavities. And what we saw was that there was this enrichment for lactic acid bacteria and many other bacteria. But they're the ones that stood out to us because they were most depleted in the disease stage. And so we moved the...
FLATOW: Is this the bacteria that you find in yogurt and things like that?
LYNCH: Yeah, yeah. It's a relative. It's one of them. There are many, many lactobacillus species. But the one that we focus on is one - actually, we focused on the one that's used in making sake. (Unintelligible).
FLATOW: Making sake?
LYNCH: Yeah. I'm not advocating putting sake up your nose but (unintelligible).
FLATOW: But you did - in the mice, you did try sort of that experiment, did you not?
LYNCH: That's true. We did, we did.
FLATOW: Tell us about that.
LYNCH: We did. We - what we did with the mice was we gave them antibiotics to deplete their sinus microbiome, and then we had them sniff, basically, the corynebacterium species. And, in that context, we saw all the hallmarks of sinus infection, lots of mucin hypersecretion from the host.
And when we did the same and added the lactobacillus species, we didn't see any hallmarks of pathogenesis or infection. And, in fact, when we did another group of mice where we took out their native microbiome, we instilled the protective species along with this pathogen that we've identified. Again, we saw no signs of infections suggesting that the lactobacillus species protected the surface of the sinus and evaded infection by the corynebacterium species.
FLATOW: Now, you know what all these public radio listeners are going to want to know, now. Right?
FLATOW: We'll have to ask it. Where do you get the stuff to snort up your own lactobacillus sake, you know? I want some of that stuff with my health food store.
LYNCH: You know, there are a number of reporters who've contacted me that have said, what do you we do? I've got sinusitis. What do I do? It clearly is a prevalent problem in the general population. But clearly, we need controlled clinical trials to determine the efficacy of these kinds of interventions. And the FDA has ruled that if we are doing such trials, we need investigational drug status for every species that we want to instill into a patient to treat our disease.
So it maybe a while before we can actually get to a point where we would be instilling these kinds of organisms into the sinuses. But it's certainly another way of thinking about treating chronic inflammatory disease, of the sinuses, at least. There's certainly prostins in the gastrointestinal tract. For example, when there's recalcitrant C. difficile, clostridium difficile infection, which is this thing that outgrows when patients have had, again, a lot of antimicrobials and have depleted diversity. Fecal transplant works very well.
So taking the feces of a spouse or a relative, and basically repopulating the gastrointestinal tract with those species, has a rate of 91 percent efficacy. So I think we could consider this for mucosal services as, perhaps, the general rule that this kind of restoration ecology approach to try to reinstate the healthy protective organisms in this niches, maybe an alternative strategy for treating some of these chronic inflammatory diseases.
FLATOW: Yeah. Did we once all have them and they went away somehow? Or what - why did some of us have the healthy population and some of us don't?
LYNCH: Well, that's all down to exposures. And, you know, one of the things that clearly can deplete a microbiome of diversity is antimicrobial use, which clearly is more prevalent in use and perhaps inappropriately.
FLATOW: Antibiotics, you mean.
LYNCH: Exactly. In the last several decades. That's clearly one obvious approach to deplete the diversity. The other thing is, we think that viral infections, which frequently perceive these kind of chronic outcomes in inflammatory disease, including in the sinuses, they may actually perturb the microbiome and induce, perhaps, inflammation from the host that actually kills some of these protective organisms.
And one of the hypothesis were working off is that we know that pathogens can induce a host inflammatory response. And they do that to, we think, generate an ecosystem in which they're fitter. And perhaps some of these beneficial organisms, if the other side of the coin, they try to modulate that immune response because they're exquisitely - exquisitely sensitive to it and are, you know, they want to, again, generate a niche in which they are fittest in. So this is one of the hypothesis we're working off at the moment.
FLATOW: Mm-hmm. And you...
LYNCH: But certainly we think...
FLATOW: Yeah. Go ahead.
LYNCH: Sorry. Certainly, we think that perhaps not just a single antimicrobial dose but perhaps there may be a cumulative effect over years of antimicrobial doses that cumulatively depletes micro biome diversity from this niches.
FLATOW: You know, as you said before, the biome that's all over our body are - is something we hardly have ever studied before and we keep discovering new things about.
LYNCH: That's true.
FLATOW: How - they were all interacting with our health system.
LYNCH: That's true. And that's just largely because the whole human microbiome research field has only emerged in the last five to seven years. It's kind of interesting that, you know, environmental and microbial ecologists had developed these methods to detect the bacteria without needing to culture them for, you know, 20, 25 years. But it's only in the last five to seven years that we've been applying these really powerful approaches to describe the types of microbe's present in human samples.
And really, that it's been outstanding, what we found even in this short period of time to date. You know, there are so many diseases - obesity, diabetes - that are now being linked to perturbations of these communities of bacteria at different sites in the human host.
FLATOW: You know, we know that there are different bacteria in your stomach, there are different bacteria in your mouth. Do they connect together? I mean, if you wanted to replenish what's going on in your nose, could you eat the lactobacillus sake and it finds its way up to your nose?
LYNCH: Yeah. It's quite interesting. There was a study, and we actually quoted it in the paper, of 300 children who were fed either a lactobacillus species or a bifidobacterium species, or a combination of the two. And this is an oral ingestion of these bugs. And those children showed significant benefit in symptoms of rhinorrhea and things associated with kind of upper airway problems, upper airway infection. And so, trying to think about how that might work, certainly it's a system. It's not - these niches are not isolators. And there was a very nice study by quantum(ph) colleagues some years ago that showed if you fed animals a mixture of probiotic species, that they primed these specific types of immune cells that dampen inflammatory responses.
And not only did they do it in the gastrointestinal tract, these anti- inflammatory cells would actually traffic to sites remote from the gastrointestinal tract, for example, the skin in a model atopic dermatitis and the joints in a model of arthritis. So clearly, the gastrointestinal tract is a prime target for, perhaps, altering immune responses at sites remote from the - that niche. Although I still think that installation in the sinus, as well, a direct installation certainly would also be an alternative approach as well, if not in combination with oral consumption of these organisms.
FLATOW: Talking with Susan Lynch, associate professor of medicine at UC San Francisco on SCIENCE FRIDAY from NPR. So you're saying, let's go right to the source. Let's not, you know, let's try this experiment in...
FLATOW: Right up your nose.
LYNCH: Assuming we know some it.
LYNCH: And that's it. And, you know, we know some of it a little at this stage. These are very early studies that are just almost like proof of principle, that clearly we're seeing the same trends across different mucosal surfaces in body. So perhaps there could be a unifying theory in this idea of restoring appropriate colonization patterns to those sites.
FLATOW: Well, let me ask you a wild question that just struck me. If you overly - if you're a mouthwash user and it kills everything in your mouth or any bacteria, 99 percent of the germs, it says, are you doing yourself a disservice?
LYNCH: I - we - nobody has looked at that. And it's - again, anything that perturbes these communities, you know, there's the potential for pathogenic organisms to outgrow in that kind of depleted diversity community. So it would be wonderful study. We don't study oral micro biota, but it would be wonderful study.
LYNCH: And certainly it has all the hallmarks for the possibility of increasing proliferation of some of these detrimental organisms.
FLATOW: Let me look closer to your nasal cavities and ask you this.
FLATOW: What about, you know, when - they always tell you we have a cold, you should gargle with saltwater or, you know, inject saltwater up your nasal passages. Clean it out, they say.
FLATOW: Now, from what I hear you saying, you don't want to clean it out. You want to get more stuff in there. You're going to be cleaning out the good bacteria, would you not?
LYNCH: Well, that is a possibility. Although if you have problems, you clearly have some bad bacteria there that would be - that you could possibly clear out as well. What we're thinking is that perhaps something like a nasal clear out with saline are indeed anti-microbial, coupled with these rehabilitation approaches. So when you it clear it out, that you reinstate the appropriate organisms at that site, that that might be the best approach we could take for treatment.
And that, you know, 15 percent of chronic rhinosinusitis sufferers are - have good outcomes and resolved their disease symptoms with anti-microbials. So clearly, we're missing a part of the picture. We're currently - there's something missing that we need to add, and we think it's restoration of these organisms that may actually maintain a balanced immune response of these site and protect these mucosal surfaces. We actually think that something kind of an equivalent of a microbial shield at these sites (unintelligible).
FLATOW: Do we each have our own biome that we could sample and figure out what's in there for later, putting it back if we lose it?
LYNCH: Yes, we do. Yes, we do. We each have a unique micro biome, and it's unique at very different sites in the human body. So it's - you've got a fingerprint in the sinuses, a very different set of organisms in the gastrointestinal tract because of the conditions there, the ecosystem there. You know, that hasn't been considered for sinus disease, but it's certainly been considered. There's been talk of fecal banking from maybe childhood or early adulthood, when individuals are healthy, for downstream use when things go awry and chronic inflammatory disease, for example, occurs.
FLATOW: Mm-hmm. Sounds like it sounds very interesting, you know? This whole topic is just fascinating, and we all wonder how they all interact with each, a topic for another SCIENCE FRIDAY because we have talked a lot about the micro biome. Thank you very much, Dr. Lynch.
LYNCH: Thank you.
FLATOW: Fascinating stuff. Susan Lynch is associate professor of medicine at UC San Francisco. She's also director of the Colitis and Crohn's Disease Micro biome Research Core there. Thanks again for joining us, and have a good weekend.
LYNCH: Great. Thank you.
FLATOW: That's about all the time we have for today. Don't forget the SCIENCE FRIDAY book club is going to meet next week and we are reading "Flatland" by Edwin Abbott. You can get your copy and get it downloaded free on the Internet. That's the book we'll be talking about next week.
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