 This research article is titled, Sinus Microbiome Diversity Depletion and Corinebacterium Tuberculosis Stericum Enrichment mediates Rhino Sinusitis. It was published by Susan Lynch's group at the University of California in San Francisco in September of 2012 in Science Translational Medicine. It made me surprising for some of you to hear that we are in fact made up of more bacterial cells than human cells. The collection of bacteria that live in our bodies, on our skin, in our intestinal tract, lungs, mouth, et cetera, are termed the human microbiome. Although some bacteria can cause disease, the bacteria that compose our microbiome are for the most part harmless. So what is our purpose? Why have we evolved to act as a host to so many bacteria? Well, the role that this microbiome is playing with regards to our health is only now starting to emerge thanks to new technological breakthroughs that I will come back to. In the microbiome, there are very many different species of bacteria and its composition is ever-changing and can be influenced by many factors. For example, what we eat, viral infections, our immune state, our general health, genetics, et cetera. So as you can see, it's often very difficult to analyze the changes in the microbiome because its composition can vary a lot from person to person and from time to time. So the Lynch Lab aimed to study the microbiome composition in the sinuses of patients with chronic sinusitis. Chronic sinusitis affects more than 30 million Americans and is defined as a state of chronic inflammation of the sinuses. We are not exactly sure what causes sinusitis, but some people have speculated that it may be caused by allergies, nasal polyps, bacterial, viral, or fungal infections, which as you can see is not very specific and for the most part we are not very sure of the exact cause. So how do we treat sinusitis in the clinic? Treatment include steroids, antibiotics, or surgery. But this is often not effective in the long term and symptoms tend to reappear. So as you can see, we still have a lot to learn about the cause and mechanism of disease to provide more targeted and effective therapies. So in this study, the scientists isolated bacteria from the sinuses of patients that happen to be undergoing sinus surgery. They collected samples from 10 patients with chronic sinusitis and 10 patients without chronic sinusitis and they looked at the types and the abundance of the bacteria that were present in each patient using an advanced method that is able to measure the abundance of over 8,500 different bacterial species. So what did the scientists find? The scientists found the sinus microbiome of healthy patients had a wide variety of different bacterial species and the distribution of the bacteria was very even throughout all of the different species. This is typical of what is thought to represent a healthy microbiome. In contrast, the sinus microbiome of chronic sinusitis patients had fewer types of bacteria and the distribution of the bacteria in the different species was very uneven. It was dominated by a few organisms. Overall, this microbiome was much less diverse. What was most surprising though was the overabundance of a specific type of bacteria, carinobacterium. Healthy patients also had carinobacteria in their sinuses but it was not as abundant as in chronic sinusitis patients. In fact, carinobacterium is very abundant on normal human skin as part of the skin microbiome. And prior to this study, carinobacterium had never been thought of as a pathogen but merely as a harmless resident bacteria of the skin. So next, the scientists were interested in seeing if the abundance of carinobacterium in the sinuses could potentially be causing sinusitis symptoms. So to do this, they used the mouse as a disease model and they treated mice a few different ways. Group one consisted of untreated mice. Group two consisted of mice that had received antibiotics since most chronic sinusitis patients received antibiotics. Group three consisted of mice that were treated with carinobacterium alone. Group four consisted of mice treated with carinobacterium and antibiotics. So what did they find? Well, the mice in groups one and two did not develop sinusitis-like symptoms. However, mice in group three developed more mucus secretions which is a hallmark of chronic sinusitis. And surprisingly, mice in group four had even more mucus secretion in their sinus cavities. So what does this mean? First of all, this means that carinobacterium is able to induce sinusitis symptoms when present in overabundance. This would explain why antibiotic treatment can temporarily alleviate symptoms in chronic sinusitis patients by killing off all of the bacteria, including the carinobacteria. But how could the presence of the antibiotics in combination with carinobacterium actually worsen the sinusitis symptoms? Well, the scientists postulated that the antibiotics are able to clear the microbiome from the sinuses and that this provides an opportunity for the added carinobacteria to take over and grow better. This suggests that something in the sinus microbiome may actually be preventing carinobacterium from growing too much and producing very severe symptoms. And in fact, there was one bacterial species that was greatly reduced in abundance in chronic sinusitis patients. Lactobacillus sacchiii. So the scientists tried adding both L-sacchiii and carinobacterium in the sinuses of antibiotic-treated mice. They found no sinusitis symptoms. So this proved that L-sacchiii prevents carinobacterium from growing too much and blocks sinusitis symptoms from appearing. This highlights the incredible level of competition that occurs in the microbiome to maintain a healthy, balanced state and to prevent the ag growth of single species, which may affect the health of the patient. So what did the study show? Overall, this study provides both a model for the development of sinusitis and a potential treatment. According to the study, chronic sinusitis may be caused by the overabundance of carinobacterium in the sinuses, which somehow activates the immune system, skewing the body towards an inflammatory state. Carinobacterium is found in normal, healthy people, so its presence is not pathogenic. What's pathogenic is its overabundance. It's still unknown exactly how carinobacterium ends up being so abundant, but it could be due to infection, weakened immune state, some other underlying disease or antibiotics. According to the study, treatment with antibiotics, although it works in the short term, could be detrimental in the long term because it could clear away some of the bacterial species that are trying to keep carinobacterium in check and may, in the long term, allow for an even greater opportunity for carinobacterium to grow and induce more inflammation and stronger sinusitis symptoms. And lastly, this study provides a potential treatment for chronic sinusitis by supplementing the sinusitis microbiome by adding more L-sacchi-i to try to return the microbiome to a healthy balance state. What was also very impressive in this study is that despite the amazing diversity of everyone's microbiome, the scientists were still able to find one single species that was overabundant that seemed to cause chronic sinusitis and one single species that was depleted that seemed to protect from chronic sinusitis in patients. So what does this mean to you? This all sounds great as a model for the cause and treatment of sinusitis and it certainly worked in their mouse system. However, the scientists induced sinusitis solely by providing carinobacteria in the mouse sinuses. This may not be the only cause of sinusitis in humans and it's definitely possible that viruses or fungi could also contribute to causing sinusitis. In which case, the addition of L-sacchi-i may not be all that effective. Also, carinobacteria may be providing some benefits when present at normal levels as part of a healthy microbiome. So its elimination may actually be harmful. And lastly, it's important to be cautious in our use of antibiotics because we may be killing off some good bacteria and allowing a few species to outgrow. And this decreases the diversity of our microbiome and could be detrimental to our health. So altogether, this study does provide overwhelming evidence that the search for a greater understanding of the role of microbiome communities in our health could lead to some very interesting discoveries related to the cause of disease, especially those involving inflammation. These discoveries then provide a basis for the design of targeted therapies for a disease microbiome. Thinking ahead, it may even be possible to profile an individual patient's microbiome and determine which species are depleted or overabundant in that individual patient that may be causing their disease, providing a step forward for personalized medicine.