The Biome of the Lung

  Of bugs and horses    A couple of weeks ago, I was on an emergency call to a training stable. Half of the horses had started coughing overnight, some had fever, and, as you’d expect when bad karma decides to make a point, the two stars of the premises, due to face their greatest challenge to date the following week, were dull and depressed. A thick and yellow discharge was oozing from their noses. It was not long before the barn became the typical scene of a bad strangles nightmare. The bacteria involved in strangles outbreaks are Streptococcus equi equi, highly aggressive and contagious germs that spread fast and cause disruption in days of training and mayhem in tight racing schedules.      So what inevitably comes to mind when you hear the words “germs” or “bacteria”? Certainly no nice and friendly terms. As veterinarians, we have been taught that microorganisms are responsible for an endless list of gruesome diseases and conditions: abscesses, pneumonia, septicemia ... you name it. All of these need to be identified and eradicated. Thank heavens we still have an arsenal of antibiotics to get rid of the damn bugs. But recent research in human “microbiome” is making us think twice, especially as we aim to hit hard and large with antibiotics.      Never alone    Your healthy and thriving self, and likewise your horse, hosts millions and trillions of bacteria. The “microbiota” is that incredibly large collection of microorganisms that have elected you and your horse as their permanent home. The microbiota is constituted not only by an extremely diverse variety of resident bacteria, but also by viruses, fungi, and yeasts that multiply in every part of your external and internal anatomy. The discovery of this prosperous microbial community has triggered fascinating new research. It has unveiled the unsuspected links that exist between health, disease, and the microbiota. In simple words, these microorganisms are vital to your strength and healthiness.      The microbes that compose the microbiota outnumber our own cells by 10 to one to the extent that the genetic information (or “genome”) you carry is over 99% microbial! And that is what researchers call the “microbiome” or “biome”: the collection of genetic information carried by your microbiota. Fortunately, the very large majority of bacteria is either beneficial or harmless, with only a very tiny fringe represented by potentially pathogenic strains. These microorganisms have evolved with us over thousands of years and the stability of this symbiotic ecosystem has important implications on our health status.       A gut feeling for biome    Research on the biome started with the study of the digestive ecosystem of mice. Researchers from Washington University showed that when they transplanted feces of obese mice in the gut of lean mice, these became obese, and vice versa. In other words, the composition of the gut biome could be said to influence morbid weight gain. Similar studies recently conducted in humans in the Netherlands came to the same conclusions. We do not yet have all the keys to understanding the underlying processes, but we definitely know that gut microbes influence, amongst many other things, our metabolism, which is to say our capacity to process energy. This opened up tremendous possibilities to improving fitness and treating diseases. The research on the biome has since grown at an exponential rate, covering much larger areas. It was further discovered that problems in the gut biome leading to the proliferation of the wrong microorganisms were responsible for a very wide range of disorders or even chronic conditions that were far from the gut, such as arthritis, depression, and asthma. The biome also seems to be critical in regulating our immune system to raise the alarm when enemies are identified and to modulate its response. The dramatic rise in autoimmune diseases could be a consequence of dietary changes that have disrupted our healthy microbiota.      The lung biome    Each organ, from the gut to the skin, hosts a specific biome; even the respiratory tract has its own “biomic” population. It was initially believed that healthy lungs were sterile, as samples taken from the lower airways did not yield any bacterial or fungal colony growth and cultures would only come back positive in cases of infection, such as pneumonia. With the development of culture-independent techniques, which have become cheaper and more readily available, research is now showing that the lower respiratory tract entertains a rich microbial community: the lung biome. It is increasingly clear that the biome present in a healthy lung can be very different from that of diseased lungs. It would be logical of course in cases of infection, but it also seems to appear in more chronic ailments such as cystic fibrosis and asthma. The healthy biome can be significantly disrupted by smoking, pollution, or the use/abuse of antibiotics.      In humans, the lungs of a fetus are allegedly sterile, meaning free from any microbe. Immediately after birth, the lung microbiota is seeded through contact with the mother’s microbes. The microbes rapidly colonize all mucosal surfaces of the infant. The colonization is first identical across the different body sites and organs, but within days, the microbiota quickly differentiates into site-specific communities. In the lungs, the quality of the environment plays a pivotal role in selecting the biome. Similar processes would occur in other mammalian species, such as horses.      Who’s who    To characterize the lung biome, it is necessary to sample the airways. The biome is usually harvested and studied from BAL samples (broncho-alveolar lavage). Because of the variety and complexity of the microorganisms present in the airways, these are grouped into categories which scientists call phylae. They carry strange names such as Firmicutes, Bacteroides, or Proteobacteria, with the most common genera being Streptococcus and Pseudomonas.      The lung biome, which is believed to be stable (or at least temporarily) in healthy subjects, is now being considered as an evolving microbial population, which may, in given circumstances, evolve to cause disease. Initially, the research studies on the respiratory microbiome focused on bacteria and the impact they could have on lung health. But it has become apparent that the bacteria represents only part of the entire biome and that other non-bacterial organisms, including viruses and fungi, are as likely to play a role in the regulation of health and disease. Fungi have always been tricky to culture and identify: they are modest and bashful little microbes and will only grow when asked nicely, given the right conditions. Thanks to advances in next-generation sequencing, a number of fungi which had not been previously detected by culture methods have been identified in the lungs. As a result, the fungal lung biome has been under keener scrutiny. There is more and more evidence that it has a significant clinical effect in cases of chronic respiratory diseases such as asthma or chronic obstructive pulmonary disease.      To thicken the plot further, the fungal and bacterial biomes interact and team up and develop the capacity to fiddle with their host’s immune response, causing inflammation and disrupting lung function, thus essentially actively participating to the progress of disease. There is a highly complex network at stake: despite geographical distance it now seems that the lung biome and the gut biome are in constant communication and interaction: like the political leaders of two superpowers, they sometimes ally and sometimes declare war (to each other or to their host).      Asthma and the lung biome    Asthma is one of the most studied diseases in human medicine. It is a particularly unpleasant condition in which the airways swell, tighten, and produce extra mucus, making the simple act of breathing difficult and sometimes anxious. Horses also suffer from asthma: inflammatory airway disease, heaves, and “COPD” have now been recognized as being various forms of equine asthma. Any form of asthma, even milder forms, can markedly reduce a horse’s performance and, in more acute forms, be debilitating. Here is the respiratory system overreacting for you, often in the face of a dusty and contaminated environment.    Even if the symptoms of asthma can be controlled, the underlying condition itself can never be definitively cured.      Studies on the human lung biome have reported major differences in the microbiota of asthmatic patients in comparison to healthy controls. There appears to be a greater bacterial diversity and burden in asthmatics, with the severity of the disease and degree of airway “hyperreactivity” correlating to the amount and diversity of certain biome warlords. Another study carried out on infants demonstrated that those with lungs contaminated by harmful bacteria after birth were at an increased risk of developing asthma compared with infants who were not born with the harmful bacteria in their lungs. The battle between good and evil takes place at the microscopic level, deep within the remotest dead-end airways.      The science of lung biome in the equine species is still in its baby years. A Canadian group of researchers has very recently been looking at the effect of environmental conditions on the biome of the entire equine airways, from nose to lungs, and has compared the biome of healthy horses with that of asthmatic subjects. The study reveals that horses kept at pasture had very different biomes in comparison to horses kept indoors. Besides, the lung biome of the asthmatics differed considerably to that of horses free from asthma when they were housed together indoors. However when all horses were out at pasture, the differences were far less perceptible. The first steps have been taken to describe what happens when the disease occurs in horses. We now have to make sense of the meaning of these findings, how we can keep the biome in good shape and avoid going down the slippery slope of disease.      Keeping the biome happy    One thing that scientists working in this field agree upon is that it is paramount to nurture a healthy biome. Dysbiosis -- the disruption of the biome -- is a cause of disease. For horses and their caretakers, keeping a healthy lung biome means keeping an overall healthy environment: the higher the burden in dust, particles, noxious gases, or contaminants, the higher the chance of messing up the biome.    Other stressful factors to the biome may be dehydration, transportation, and mingling with other horses, who are carrying different and potentially problematic germs. Anything that affects the balance of the airway’s microbial ecosystem will inevitably open the door to infection, inflammation, or immune disorders.      Truly potent and deadly enemies of the biome are antibiotics. Giving antibiotics kills bacteria, both good and bad, without distinction. The un-circumspect administration of antibiotics or antiseptic solutions can upset a healthy microbiome for years and predispose the horse to developing chronic infections or even possibly asthma, as it has been demonstrated in humans. Let’s hope that continued research in the field of lung biome will provide us with new insights both into our understanding of the mechanisms causing respiratory diseases as well as in the role the lung biome plays in respiratory health.      This research could even pave the way to new treatment approaches! If we look at treatment options for gut “dysbiosis” in patients that harbor antibiotic-resistant harmful bacteria in their intestines, we now have “fecal transplants.” Radical but highly effective, fecal transplants consist of installing a healthy person’s microbiota into a sick person’s gut. I’ll let you imagine how it can be done. As disgusting as it may seem, it has been a lifesaver for patients in highly critical conditions. That’s the power of a healthy biome. Perhaps there will soon be new ways of treating and controlling lung diseases in our horses through modulating their lung biome.

By Dr. Emmanuelle van Erck-Westergren, DVM, PhD, ECEIM

Of bugs and horses

A couple of weeks ago, I was on an emergency call to a training stable. Half of the horses had started coughing overnight, some had fever, and, as you’d expect when bad karma decides to make a point, the two stars of the premises, due to face their greatest challenge to date the following week, were dull and depressed. A thick and yellow discharge was oozing from their noses. It was not long before the barn became the typical scene of a bad strangles nightmare. The bacteria involved in strangles outbreaks are Streptococcus equi equi, highly aggressive and contagious germs that spread fast and cause disruption in days of training and mayhem in tight racing schedules.

So what inevitably comes to mind when you hear the words “germs” or “bacteria”? Certainly no nice and friendly terms. As veterinarians, we have been taught that microorganisms are responsible for an endless list of gruesome diseases and conditions: abscesses, pneumonia, septicemia ... you name it. All of these need to be identified and eradicated. Thank heavens we still have an arsenal of antibiotics to get rid of the damn bugs. But recent research in human “microbiome” is making us think twice, especially as we aim to hit hard and large with antibiotics.

Never alone

Your healthy and thriving self, and likewise your horse, hosts millions and trillions of bacteria. The “microbiota” is that incredibly large collection of microorganisms that have elected you and your horse as their permanent home. The microbiota is constituted not only by an extremely diverse variety of resident bacteria, but also by viruses, fungi, and yeasts that multiply in every part of your external and internal anatomy. The discovery of this prosperous microbial community has triggered fascinating new research. It has unveiled the unsuspected links that exist between health, disease, and the microbiota. In simple words, these microorganisms are vital to your strength and healthiness.

 

The microbes that compose the microbiota outnumber our own cells by 10 to one to the extent that the genetic information (or “genome”) you carry is over 99% microbial! And that is what researchers call the “microbiome” or “biome”: the collection of genetic information carried by your microbiota. Fortunately, the very large majority of bacteria is either beneficial or harmless, with only a very tiny fringe represented by potentially pathogenic strains. These microorganisms have evolved with us over thousands of years and the stability of this symbiotic ecosystem has important implications on our health status.

A gut feeling for biome

Research on the biome started with the study of the digestive ecosystem of mice. Researchers from Washington University showed that when they transplanted feces of obese mice in the gut of lean mice, these became obese, and vice versa. In other words, the composition of the gut biome could be said to influence morbid weight gain. Similar studies recently conducted in humans in the Netherlands came to the same conclusions.

We do not yet have all the keys to understanding the underlying processes, but we definitely know that gut microbes influence, amongst many other things, our metabolism, which is to say our capacity to process energy. This opened up tremendous possibilities to improving fitness and treating diseases. The research on the biome has since grown at an exponential rate, covering much larger areas. It was further discovered that problems in the gut biome leading to the proliferation of the wrong microorganisms were responsible for a very wide range of disorders or even chronic conditions that were far from the gut, such as arthritis, depression, and asthma.  The biome also seems to be critical in regulating our immune system to raise the alarm when enemies are identified and to modulate its response. The dramatic rise in autoimmune diseases could be a consequence of dietary changes that have disrupted our healthy microbiota.

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Noah Abramson

Trainer of the Quarter - Kellyn Gorder

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