Our microbiome and how it keeps us healthy

00:00:00: Digestive problems are on the rise and they are directly linked to our modern way of life.

00:00:08: What makes life easier for us is ruining our bodies.

00:00:11: Fast food, sitting at work, in the car, on the couch.

00:00:16: The need for exercise is diminishing and all of this is harming our tiny little housemates.

00:00:23: After all, we are not alone in our bodies.

00:00:27: The huge community of microorganisms in our guts keeps us healthy.

00:00:31: And when things go wrong, we get sick.

00:00:35: And not just a little.

00:00:37: Disruptions to our microbiome could trigger morbid obesity, diabetes, inflammatory bowel

00:00:43: disease and even depression and cancer.

00:00:47: Lisa Osbelt-Block knows this.

00:00:49: She's a researcher at the HZI and is fascinated by our little coin habitants.

00:00:55: Our host, Julia Damon, talks to her about how our microbiome keeps our bodies healthy

00:01:01: and what happens when it's out of whack.

00:01:04: She also talks about her latest research into the microbiome and how it could be used to

00:01:09: treat diseases.

00:01:13: I'm here in the library of the HZI in Braunschweig with microbiome researcher Lisa Osbelt-Block.

00:01:19: Hi, Lisa.

00:01:20: First of all, let's talk about some basics regarding our microbiome.

00:01:24: So what exactly is the microbiome?

00:01:27: Like, what does it consist of?

00:01:29: Why is it important for us?

00:01:31: And when do we get our first microbiome?

00:01:34: First of all, it's important to say we are not alone.

00:01:37: So we are colonized by billions and billions of microorganisms throughout our whole body.

00:01:44: So our skin, for example, but most importantly, the gut is densely colonized with various

00:01:49: microorganisms.

00:01:50: And this is not only bacteria.

00:01:52: So we are focusing on bacteria here, specifically in our research group.

00:01:57: But the microbiome is more than that.

00:02:01: Also our here or fungi, for example, protozoa, so very simple eukaryotic microorganisms are

00:02:09: part of these complex ecosystems.

00:02:11: And this is what the term microbiome actually means.

00:02:14: So it's an ecosystem of various microorganisms.

00:02:19: And also they are produced substrates, for example, building a kind of organ, actually.

00:02:26: This is very important for our health.

00:02:28: So the microbiome helps us to digest food, which is otherwise indigestible.

00:02:34: So the microorganisms split fiber into smaller particles, for example.

00:02:40: They produce vitamins, vitamin B, vitamin K.

00:02:44: They are important for the intestinal bowel movement.

00:02:48: They are important to really get the energy out of the food.

00:02:52: So very basic digestible function is only possible with these microorganisms inside

00:03:00: our bodies.

00:03:01: And most importantly, these bacteria confer resistance against infections.

00:03:07: What does that mean?

00:03:08: It means that the bacteria inhabit the intestine and thereby block actually the space for external

00:03:15: invaders, so-called pathogens, that can otherwise just grow out and infect us.

00:03:22: So they are really, really important for our health.

00:03:26: And on top of that, they are also in close contact with our immune system.

00:03:30: So they are training our immune system what is harmful, what is harmless, for example.

00:03:36: So they are very basic microorganisms, but also a variety of mechanisms that are conferred

00:03:42: by these microbes.

00:03:44: And to answer the question whether it's already there from the beginning, it's not.

00:03:48: It's developing over time.

00:03:50: So we are born completely sterile, but then get in contact during birth with the vaginal

00:03:56: microbiome of the mother.

00:03:59: And this is then the very initial colonization of the newborn.

00:04:03: On the other hand, if you are born via cesarean section, for example, the situation is a bit

00:04:09: different and actually also unfavorable for our development.

00:04:12: So we get in contact more with the skin microbiome of the mother and also with germs in the,

00:04:17: let's say, general environment of the hospital.

00:04:21: And this actually has like long and lasting impact on the development of the microbiome.

00:04:27: So starting from this very simple communities, the microbiome actually develops over time

00:04:34: into more complex and complex communities and those stabilize at the age of three, so

00:04:40: to say.

00:04:41: So a three year old has a comparable microbiome to an adult, but this is not, let's say,

00:04:48: always fixed.

00:04:49: It's really like changing over time.

00:04:53: There's different environmental factors that influence the microbiome composition.

00:04:58: And yeah, this is how it goes.

00:05:02: Actually which bacteria and viruses cause infections and which ones are beneficial for

00:05:07: us or even help us to cure.

00:05:10: And is it even possible to generalize this?

00:05:13: It's not really possible to generalize it even though there is some basic principles

00:05:18: I can elaborate on.

00:05:19: So there is some bacteria that are for sure beneficial.

00:05:23: These are called symbionts.

00:05:25: There are ones that are, let's say, rather neutral.

00:05:28: They do not harm us.

00:05:29: Those are called commensals.

00:05:31: There are some that are sometimes a little bit harmful and at certain circumstances, those

00:05:36: are the patobionts, but they are part of the natural microbiome still.

00:05:39: And then there's external troublemakers, invaders that actually harm us and make us

00:05:44: ill and those are the pathogens.

00:05:47: Overall, the community should consist, of course, of the more beneficial ones or let's

00:05:52: say the harmless ones rather than the potential harmful ones.

00:05:56: And usually most of them are oxygen-sensitive bacteria, so called anaerobic bacteria.

00:06:03: But the overall community structure is very, very individual.

00:06:07: So you have a different microbiome than I have and actually it's more like a microbiophingerprint.

00:06:13: It's really difficult to generally apply broad mechanisms that apply for everyone.

00:06:17: It's rather personalized and very individual.

00:06:20: But even within myself or in one person, it's very diverse biodiversity in the microbiome

00:06:27: so important.

00:06:29: Biodiversity is also in the usual life, is very important in that regard that microbes

00:06:34: have different functions.

00:06:36: If we just think of ourselves, we are not good at everything.

00:06:39: So there is one person that has like favorite painting skills, there is another one who

00:06:46: can like run very fast.

00:06:49: There are really like generalists that can do everything but not very good.

00:06:54: And they are highly specialized people that are like really outstanding in one particular

00:07:00: field and this also applies to the bacteria.

00:07:03: So it's rather a team sport.

00:07:05: We need bacteria with different functionalities that can complement each other and thereby

00:07:10: they really block efficiently all the available nutrients and spaces and create kind of a

00:07:17: barrier that makes it difficult for external invaders to really find their space and establish

00:07:23: in this community.

00:07:24: Wow, okay.

00:07:25: And how does the microbiome react to prebiotics and probiotics that we actually eat?

00:07:32: So maybe to just give a brief definition of these both terms.

00:07:37: So prebiotics are actually substances like fiber for example that actually favor the

00:07:46: outgrowth of more beneficial bacteria.

00:07:48: So we try to feed the good ones only.

00:07:51: And probiotics are living bacteria actually that we try to apply directly to really supply

00:07:57: the good ones that eventually then invade our body and establish there and gives us

00:08:04: health benefits.

00:08:06: But we have to say that probiotics in itself come maybe like from yogurt something like

00:08:12: this and they can not really establish in our microbiome.

00:08:16: So they only give like temporarily benefits to us and that we got during the intake so

00:08:22: to say.

00:08:23: So we have to eat it every day.

00:08:25: Exactly on a regular basis.

00:08:27: And for prebiotics it's actually the case that there is actually clinical hints that

00:08:32: constant supplementation and also here it's important to like really continuously eat

00:08:37: it that you can really have impact on the beneficial one and give them a fitness advantage

00:08:44: over the bad ones.

00:08:45: So I would say you can do it.

00:08:47: It does not harm but I doubt that all the marketing let's say effects that are promoted

00:08:55: there are really helpful.

00:08:59: So I think I now can understand why this topic fascinates you but how did you get into microbiome

00:09:05: research what actually fascinates you about it.

00:09:09: I think microbiome is one of the most exciting fields in basic research because nevertheless

00:09:17: we have a lot of advanced techniques.

00:09:21: We cannot really understand this immense complexity and unravel all the underlying mechanism how

00:09:28: the microbes talk to each other.

00:09:30: Why are ones important.

00:09:32: Why is another important another circumstance.

00:09:36: So it's really like immensely complex and this fascinates me because I also like to

00:09:42: do some riddles and sources.

00:09:44: So this is why microbiome is really fascinating in itself and also the fact that we are colonized

00:09:51: by trillions of little tiny microorganisms that actually can change our health and actually

00:09:56: can even change our feelings.

00:09:58: This is a really exciting fact that actually microbes can influence our behavior.

00:10:05: Since that depression is actually driven by changes in our microbiome I think.

00:10:10: And what exactly are you currently researching.

00:10:13: So we are currently trying to understand which particular bacteria do confer colonization

00:10:20: resistance which means which are important to be protected against infection because

00:10:26: we have to imagine not every one of us gets infected just imagine sitting in a train where

00:10:32: all the coughing people are around us some of us will get infected the other not and

00:10:37: why is that.

00:10:38: So to really understand which are the important ones and then to understand if we have identified

00:10:44: promising candidates to understand how they interact with others because the microbes are

00:10:49: not really like sole players they are team players so they actually only confer the

00:10:54: good properties if they are in close contact with the team so to speak.

00:10:59: And to develop and advance this further to eventually get a microbiome based therapy

00:11:05: for certain type of diseases that would be the overall goal.

00:11:09: And which model systems do you use are you working with.

00:11:13: There is different model system we are currently using so we have very simplified models where

00:11:19: we just use one good bacteria versus one bad bacteria put them put them together in like

00:11:25: a nutrient solution and see who wins basically.

00:11:29: Then we can scale it up to simple communities of like around 20 different microbes we put

00:11:35: together into this nutrient solution again and see what happens over time. If they grow,

00:11:41: who establish first, who is the fastest, what happens if we take out one bacterium or adenazer

00:11:48: bacterium, how actually they are interacting. What we also do is that we really receive

00:11:55: feces from healthy volunteers or also from deceased people and put in bacteria which are

00:12:02: example antibiotic resistance or otherwise pathogenic and see whether these bacteria can

00:12:06: establish in the feces or whether they are inhibited or whether they can grow out very easily.

00:12:12: And those microbiomes then that are protected are of particular interest and those are then

00:12:17: tested further in a more complex model system which is a mouse because in the simplified

00:12:24: systems we have not the impact of the diet, we have not the immune system and this is also very

00:12:30: important because as I just said it's very complex, very complex community that interacts

00:12:36: with the host and in this case the human. But in a mouse we have at least the whole organism to

00:12:43: study and there we use mice with let's say very simple communities so they are

00:12:48: bred with only 12 bacteria that represent the major bacteria that are let's say in a healthy

00:12:54: mouse microbiome and there we can then add particular candidate bacteria and see whether

00:13:00: they really confer the resistance against an infectious pathogens and one step further what

00:13:05: we also have and what I think is pretty amazing. We have mice that are bred completely sterile so

00:13:12: they are a void of any bacteria and there we can like transfer the interesting let's say poop

00:13:19: samples that we identified in the other screening essays and transfer them into the jump free mice

00:13:25: and then see how the microbiome established there in a mouse and what happens if we challenge

00:13:30: then these humanized mice with a human pathogen whether they are protected or not and this helps

00:13:36: us to really unravel the underlying mechanism. How can the balance between the host and for example

00:13:43: the mice or humans and the microbiome how can this be disturbed? Yeah I mean this is a

00:13:48: question where I cannot really give a simple solution so there's tons of factors that can

00:13:56: influence and also actually disturb this very let's say sensitive ecosystem so imagine if you

00:14:04: take an antibiotic I think it's already kind of known that this antibiotic will not only kill the

00:14:10: bad one but it also has a massive impact on good ones actually and this really then leads to a shift

00:14:18: of the community so that the good ones that actually should be most microbes are then

00:14:25: decreased and give then space for for example for pathogenic bacteria that they can outgrow and

00:14:31: outcompete the good ones under these conditions. Besides antibiotics also other type of medication

00:14:38: can actually influence our microbiome so actually one fourth I think of all non-antibiotic drugs

00:14:45: have been demonstrated to actually have an impact on at least one species or one let's say

00:14:52: type of bacteria in the gut so there is really like massive changes due to the medications that you

00:14:59: have to actually take on a daily basis for example painkillers. Beside of that also our

00:15:06: diet has a big influence so in the modern let's say kind of industrialized world we have highly

00:15:11: processed food, high sugar, high fat diets that actually are not good for our microbes so there

00:15:19: are ones that are starving that really don't get the required food anymore. There are ones that

00:15:25: really rely on fibers for example and if we do not feed them with fibers they just die out.

00:15:30: It's like mass extinction in our microbiome yeah it's really it's really bad and also the

00:15:37: hygienic conditions for example we just talked about the caesarean section babies for example but

00:15:42: all of that will lead that our microbiomes are really less diverse in comparison to other

00:15:48: populations of people that really live more in a rural kind of world like in Africa for example

00:15:54: or in South America so yeah there is a lot of factors that can actually bring it out of balance.

00:16:00: Wow and which role do commensal bacteria, you mentioned them before, play in microbiome infections

00:16:08: and in the interplay between hosts and microbiome? So commensal bacteria kind of have like double

00:16:14: role I would say so they of course produce some substances so they have like different kind of

00:16:21: metabolism and then they produce yeah different sort of substance that can then be utilized

00:16:27: in turn by pathogens and they then can grow out for example but I think the most important part

00:16:33: is that they actually block niches that are otherwise taken by pathogens. Just one example if

00:16:41: you have this buffet for example and there is two pieces of cheese left and we have a cheese loving

00:16:48: bacteria it will go there and eat it all I mean they are not altruistic bacteria I mean they don't

00:16:52: leave for the next one and if they have just taken it all the pathogens do not have any cheese

00:17:00: to grow there and this is why they can be wiped out and they cannot establish so really this space

00:17:07: competition is a very basic but important concept how commensals actually compete with

00:17:16: pathogenic bacteria. Yes very interesting and regarding your research and the future what new

00:17:23: microbiota associated therapies are potentially imaginable? Maybe coming from the past what is

00:17:30: actually known for a very long time is that you can transfer a whole microbiome from a

00:17:34: from a healthy person into a deceased person and cure for example diarrheal diseases and this is

00:17:41: actually done already in individualized healing attempts also in Germany where you just transfer

00:17:48: the whole poop from a healthy donor into a deceased person then can cure recurrent clostridiodis

00:17:56: difficile infections so you just have to imagine these people suffering from diarrhea over and

00:18:03: over they have to take antibiotics over and over and nothing is working because the microbiome is

00:18:08: really like depleted like completely out of balance but then it's really like an organ transplant

00:18:14: kind of say you put the whole microbiome into this deceased person and in 80 to 90 percent

00:18:20: this person is cured and does not have problems anymore and this concept if you understand better

00:18:26: which bacteria actually the important ones could be applied to various other diseases for example

00:18:32: chronic inflammatory bowel disease for example maybe even the diabetes maybe even cancer I mean

00:18:39: you could envision like a tons of diseases that are associated with the microbiome if you just

00:18:44: understand which bacteria are really the important ones and which mechanisms are maybe out of place

00:18:50: in this deceased people you can try to reestablish by refeeding specific bacteria with a specific

00:18:56: functionality do you think it's possible to maybe one time live without antibiotics rather not

00:19:04: I have to disappoint you I would like to say that I mean I'm not against antibiotics antibiotics

00:19:11: are super important and will be super important to treat life-threatening infections but we have

00:19:17: we have to reduce antibiotics in that cases where they are not urgently required for example

00:19:23: in farm in the middle or if you feel a little unwell go to your position and he just prescribes

00:19:32: a broad spectrum antibiotic but without even knowing whether you have a bacterial infection but

00:19:38: but rather a viral infection maybe and then it's not even working so there we have really room

00:19:42: for improvements but I have to say in Germany we are doing quite well I would say in the clinics

00:19:48: there is like methods like antibiotics stewardship or screening of patients that you really diagnose

00:19:54: which bacteria are colonizing a patient and then eventually lead to an infection to really

00:20:00: have antibiotics in a more targeted way but in other countries there you can just get your

00:20:06: antibiotics in a drugstore just without even a receipt so I think there there is room for

00:20:13: improvements still in these countries but we won't have our lives without antibiotics that for

00:20:18: sure so we still need them but maybe we can try to reduce them and also counteract this rising

00:20:25: problem of antibiotic resistances. Okay thank you this was about research and before about the

00:20:31: microbiome the basics so now let's talk about our daily life can you give us some like recommendations

00:20:39: for maintaining a healthy microbiome based on current science? I don't know it's it I just

00:20:45: I told you that it's very individual so it's difficult to really give general broad concepts

00:20:52: but what I can say of course is that you should eat healthy so whole grain products maybe fiber

00:20:59: rich diet so really come back from these let's say fast food driven kind of diet do not eat so

00:21:08: much sweets for example maybe eat like more fermented food this is really good and I mean

00:21:16: also yogurt yogurt is also good but then also try to reduce stress maybe in your daily life I know

00:21:22: it's difficult I mean with your daily work life balance and then also like do exercises not just

00:21:29: sitting around doing nothing so in your free time trying to have a nice walk in the outside area.

00:21:36: And how do you manage this to implant all this in your certainly stressful everyday research life?

00:21:42: I wouldn't say I'm a role model in that regard so there's definitely room for improvement also on

00:21:49: my side I mean I love sweets for example even though I know it's not good for my microbiome

00:21:54: but I think it always has to be in balance I mean you can eat also unhealthy one day but the next

00:21:59: day maybe try to eat more healthy eat fruit vegetable and whole grain products again and also

00:22:06: really I try to find space for other hobbies in my free time which really countered this

00:22:13: that thing at the PC behavior so I go out for a ride for example I have horses or I go running or

00:22:20: swimming and this really helps to keep your microbiome also in balance. Thank you very much

00:22:26: for all the information about our microbiome and especially for the insights into your research

00:22:33: on this subject. Yeah you're welcome what's the pleasure. Lisa Osbergblog is researching

00:22:38: how our microbiome keeps us healthy what disrupts the microbiome and what consequences this has

00:22:45: for our health and also how these findings can be used to better treat diseases in the future.

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