What We Know about the Microbiome

Not that long ago, physicians believed that healthy sinuses were sterile environments. Scientific advances have since revealed that the sinuses, like other parts of the body, are home to vast numbers of microbes. These microbes live in distinct communities, called microbiomes, which may be the key to understanding and developing effective treatments for chronic rhinosinusitis and other ailments.

“We have some evidence that the population of the microbiome does contribute to disease and inflammation within the nose and sinuses,” said Eugene Chang, MD, vice chair of the department of otolaryngology and director of rhinology and skull base surgery at the University of Arizona in Tucson. However, Dr. Chang and others say it will probably be years before microbiome research alters treatment paradigms.

“We’re still a long way from knowing if we can manipulate the microbiome and if it truly presents opportunity as a new therapy,” said Vijay Ramakrishnan, MD, associate professor of otolaryngology at the University of Colorado in Denver. “There’s a phenomenon that happens whenever new major discoveries happen in science and new tools are available to researchers. Take genomics, for instance. Everyone gets excited. We thought genes were going to be the answer to everything.”

In reality, there are still many questions to be answered about the microbiome and its role in otolaryngology. Here’s what we know so far.

Dysbiosis Associated with Chronic Rhinosinusitis

The sinus microbiome varies widely among individuals. “If you look at 10 different people, the difference between one person and the next would be so large that it’s hard to know if differences are the cause of disease or if they are related to symptoms or past treatment,” Dr. Ramakrishnan said.

However, a number of research studies to date have linked decreased microbial diversity with chronic rhinosinusitis (CRS). A 2017 study that compared 59 CRS patients with 10 healthy participants found that the bacterial burden was similar for both groups. The patients with CRS, however, “exhibited significantly lower microbiota richness, evenness, and diversity.” Researchers also noted that alpha diversity in CRS patients was more pronounced in those with concomitant lower airway disease (Microbiome. 2017; 5:53).

“One overall theme we see is dysbiosis in the community,” said Emily Cope, PhD, co-author of the study and assistant director at The Pathogen and Microbiome Institute at Northern Arizona University in Flagstaff. Dysbiosis can take different forms, Dr. Cope said. Sometimes, there is overrepresentation of certain pathogenic bacteria. Other times, there’s an overall decrease in microbial diversity. Still other studies have shown fragmentation of ecological networks.

Interestingly, studies done so far have not revealed any consistent differences in the microbiomes of people with CRS with polyps vs. CRS without polyps. “We expected to see a difference, but two studies now have shown that’s not the case,” Dr. Ramakrishnan said.  Given that clinicians typically treat CRS with polyps differently than CRS without polyps, the lack of significant differences in the microbiome may mean that these two presentations of CRS have more in common than not and should perhaps be handled similarly. Or, Dr. Ramakrishnan said, “it could mean that the microbial differences we’re observing are kind of irrelevant.”

The key question that has not yet been answered is, “Do alterations in the microbiome cause disease, or are they a side effect of the disease process?” Dr. Chang said that, “ideally, if you wanted to look at that question, you would wipe a subject clean of their microbiome and then insert a microbiome that’s dominated by pathogens to see if that causes diseases. You’d also want to find somebody with chronic sinus disease, completely deplete the microbiome, and observe what repopulates over a period of time.”

A 2012 animal study by Susan Lynch, PhD, director of the Colitis and Crohn’s Disease Microbiome Research Core at the University of California–San Francisco, demonstrated that altering the sinus microbiome may indeed contribute to the presence or absence of disease. Her team used antibiotics to deplete the sinus microbiome of mice. Corynebacterium tuberculostearicum, a bacterium that has been noted in abundance in the microbiome of CRS patients, was instilled into the sinus cavities of some mice; Lactobacillus sakei, a bacterium that’s abundant in the healthy sinus mucosal samples, was instilled into the sinuses of other mice. Mice who received C. tuberculostearicum developed evidence of sinus infection, including mucin hypersecretion. The mice who received L. sakei remained healthy. (Sci Transl Med. 2012; 4:151ra124).

At present, though, it’s not possible to do such studies with human participants.