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Ashley's Biggest Takeaways

• Babies are essentially sterile at the moment of birth, but in the first moments of life, when they pass through the birth canal, they start acquiring microbes from their mothers.
• Those microorganisms partner with human cells and play an important role in the biology of development.
• There is increasing evidence that the microbiome is involved in immune, metabolic and cognitive development.
• Across urbanization gradients, scientists are observing a decrease in diversity of the gut microbiota, while simultaneously observing an increase in inflammatory diseases. Researchers think these observations may be connected.
• Microbial diversity is decreasing due to environmental factors and the loss of ancestral microorganisms.
• Perturbations to the microbiome through environmental factors and/or antibiotic use are being linked to a variety of diseases, including type 1 diabetes, asthma, obesity, allergies and other inflammatory disease.
• This diversity in the microbiome among people in the world is not defined by diet, geography or ethnicity.
• The critical factor contributing to microbiome diversity among people around the globe is their level of urbanization and modern lifestyle.
• Understanding our relationship with microbes will be crucial for optimizing human health during development and for prolonging life.

Featured Quotes:

Gloria: My focus is to study good microbes, the microbiome and how the microbiome is assembled in early life. What are the factors that alter this assembly and the maturation as the host develops? Also, I'm interested in studying the effects of stressors on the microbiome stressors that are related to modern lifestyle, and very much in particular C section and breastfeeding. So early life stressors that may alter the transmission of human microbes between generations.

Martin: And my origins in the microbiome are a little different. Almost 40 years ago, I began studying a bacteria that lives in the human stomach called Helicobacter pylori. It was discovered as a pathogen causing ulcers. We, and others, did work showing it was a pathogen causing a stomach cancer, and everybody in the world wanted to get rid of it. But it became clear to me, and to others, that this is an ancient organism that has been disappearing gradually from people. And I thought, well, if one organism is disappearing, maybe there are others.

Martin: Then I thought maybe that's what's fueling all of our modern plagues, the plagues of asthma and obesity and food allergies—the list goes on. So I got involved in the microbiome to really test the hypothesis that our modern diseases have something to do with this loss of microbes and microbial diversity.

Martin: We were very interested in the organisms in early life that babies are acquiring now, compared to what they used to acquire a bit are babies and other societies, and how this may have a bearing on how they develop important physiology, their metabolism, their immunity, and their cognition.

Gloria: Across urbanization gradients, we observe that people decrease their gut microbiota diversity. And concomitantly they increase the risks of metabolic and immune diseases that have a common denominator, and that is inflammation. We think these two observations are correlated—that microbes are involved in the genesis of these diseases.

Gloria: We know that the humans develop until they're 18 years of age. We know that the microbiota develops very fast during the first 3 years. It doesn't mean that [the microbiome] doesn't continue assembling and developing and maturing. But the very important process is during early life.

Martin: It has become clear for many people's work, that the microbes that children acquire are not random. There is a choreography. Some microbes come first, and then others. It's a succession. It's an ecological succession. And both Gloria and I have been interested in how that succession can be disrupted.

Gloria: Pioneer microbes that babies see at birth, are maternal, because the first microbes that each one of us saw were our mother's vaginal microbes. So we can track back the pioneer exposure on the maternal line. And I think that's very awesome. It's kind of mitochondrial Eve, parallel, and those microbes are adapted in humans to be boosted by breast milk.

Gloria: During birth, there are factors that alter transmission, such as antibiotics during birth, C-sections—being born sterile into the air of the operating room—and lack of breast feeding. And then later in life, highly processed foods and lack of natural and processed vegetables fibrous sources, drinking chlorinated water and excessive sanitation, lack of exposure to nature. So we think it's a compounded effect of many stressors that may be affecting a very complex process.

Martin: There are 2 factors here that we're concerned about. One is about the loss of ancestral human organisms. And the other is about those environmental organisms.

Martin: Even before the microbiome was essentially discovered, there were observations that kids born by C-section were more likely to develop juvenile diabetes and more likely to develop obesity. In recent years, there have been studies of kids getting a lot of antibiotics being more likely to develop asthma and be overweight and develop obesity and neurodevelopmental abnormalities. So the epidemiologic data points us toward a perturbed microbiome being the cause, where the proximal cause is C-section birth, or antibiotics—or both.

Gloria: The effects of antibiotics on obesity are very clear in farm animals. Farmers were using antibiotics because they are growth promoters, and animals gained fat and were ready to be sold earlier. So it's not surprising that we may be doing the same thing to our kids by perturbing transmission of the human microbes in early life.

Gloria: The diversity of diseases is big, you know, we find increased risks of asthma, allergies, type 1 diabetes, inflammatory diseases of interest in obesity—but they all have 1 common factor, and that is higher inflammation than normal.

Martin: Another way to look at it is that we humans, like other animals, have evolved in relationship to our microbiota. And our normal microbiota has selected our innate and adaptive immune responses. Let's just say it has been stable, you know, for the last 100,000 years, or last million years, by and large. And now all of a sudden, in half a century or a century, we very much change that early life microbiota. It's like, if we think about a lock and a key, well, now it doesn't fit quite as well. And now there are consequences in that there's derangement of normal immunological development. And some of that can be pro inflammatory.

Gloria: When you look at all the microbiomes sequences have been deposited in public databases, they cluster, not by location, geography, or ethnicity. They cluster by lifestyle.

Martin: One hypothesis is that there was an ancestral lifestyle that protected against asthma, and obesity and neurodevelopmental problems. And now, we have been impairing it. It's like the parallel process to climate change. The new functions have a cost. There was there was a hidden costs to all the modernization.

Gloria: What we think may be happening is that all these redundancies in function that the human microbiome has (so high diversity is high redundancy, and high resilience)—means you can eliminate some of the populations and still have the function. But that has a limit. There is a point in which losing functional redundancy will have consequences. And we may have hit that point.

Gloria: We need to understand our relation with microbes and when to restore.

Martin: I would like to introduce another concept to stop the damage, which is to minimize the injury as a medical doctor. I know, like many medical doctors, that we are using too many antibiotics. We've known that for a long time, but how do we stop? In some ways we've become addicted because we are over-valuing the benefits and under estimating the costs.

Martin: And that's one of the reasons we wanted to work with filmmakers to make the film The Invisible Extinction, because it's not just professionals who need to know this. The general public has to know this too. Because we're all in love with technology, we're in love with antibiotics, we're in love with C-sections. In the United States, by the time the average child is 2, they've had 3 courses of antibiotics. By the time they're 10, they've had 10 courses. And it's too much. We have to use them much more knowingly.

Gloria: We are still on time to try to understand what lifestyle factors we should maintain in populations that haven't lost them yet. Wo one thing is how to preserve cultural good practices—diet habits, exercising, exposing to the sun, etc.—but the other is how to preserve microbes before they disappear.

Gloria: We created the Microbial Vault Initiative, which is an initiative to help create local collections of specimens with microbes, starting with humans, but we plan to expand to fermented foods, soils, waters—all microbial ecosystems.

Martin: I think probiotics are going to be extremely important in the future. But it will be probiotics based on science, not based on marketing. We will have to figure out for which condition, for which person, which organism it is going to work. And then the doctor of the future is going to take that that organism off the shelf, just like we give medicines. But it’s going to take a lot of science to get there.

Martin: We're looking for a one-size-fits-all model, and that may that may not be correct. It may be that in a condition like IBD, there are 10 different variants of IBD. If you use the same treatment for all them combined, the results wouldn't be that good, because you'd be over treating some, and under treating the other. So it's really important to be able to classify much better, and then we will get to better treatments.

Links for the Episode:

• (documentary).
• (book).
• Missing Microbes: (article).
•  (YouTube).

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• Host-Microbe Biology

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