Restoring Microbial Balance Key to Keeping Sinuses Healthy

Dangerous intestinal bacteria such as Clostridium difficile have taught doctors that the failure to reconstitute a normal microbial community can increase the risk that pathogens will fill the vacuum, a concept that Dr. Goldberg said is likely also at work in the sinuses. “The real take-home message of this paper is that you can’t just get rid of what’s there,” he said. “What you’re really working toward is putting back what used to be there.”

Dr. Lynch called that concept “restoration ecology,” which she believes could be aided by new technology that provides a more complete view of what should or shouldn’t be present in a healthy microbiome. “For us, we think it’s the bright horizon,” she said.

Traditional nasal swabs and bacterial cultures grown in agar, for example, provide only a partial census of the microbial inhabitants—both pathogenic and benign—within a sinus. “It’s a completely different environment,” Dr. Goldberg said. He, Dr. Lynch and co-author Steven Pletcher, MD, associate professor of otolaryngology-head and neck surgery at the UCSF Medical Center, instead used a microarray chip spotted with the DNA of 8,500 bacterial species to survey the presence and abundance of the microbes in diseased and healthy sinuses. In CRS patients, the collaborators detected an increased abundance in Corynebacterium tuberculostearicum, which is linked to opportunistic infections in other parts of the body but wouldn’t have been apparent in an agar culture.

To get a better idea of the pathogen’s potential role, the researchers studied it in a mouse model of sinusitis. After first perturbing the sinus microbiome with antibiotics—likely disrupting the normal flora—they added the Corynebacterium microbe, generating a sinusitis-like infection. When the researchers added Lactobacillus sakei, a bacterium better known for its role in the production of Japanese sake, they prevented the infection. “So it was kind of proof of concept that the Lactobacilli were beneficial in maintaining sinus health,” Dr. Goldberg said.

Andrew Lane, MD, professor of otolaryngology-head and neck surgery and director of the Johns Hopkins Sinus Center in Baltimore, accepts the idea that the sinus ecosystem can get out of whack and that antibiotics can create unintended consequences by leading to an imbalance. But Dr. Lane said the new study hasn’t resolved whether the observed bacterial shift is the cause or the effect of CRS. He also objects to the implied simplicity that the addition of one bacterial species can worsen the condition, while the addition of another can improve it. “As more studies are done, I think this is going to be refined,” he said. “I think the general concept—that there are shifts in bacteria—is true and needs to be put in this context of inflammation and host factors and different types of disease.”

Experimental Therapies

How might the inflammation versus infection debate be resolved? “Boy, that’s the million-dollar question,” Dr. Lane said. Studying patients longitudinally to examine potential microbiome shifts might provide better insights, though he cautioned that clinicians might need to keep those patients off antibiotics or steroid sprays to avoid skewing comparisons between a normal and abnormal bacterial profile. Narrowing the focus to patients with chronic, recalcitrant sinusitis that isn’t due to a blockage may also help. Dr. Lane’s lab is now collecting microbiome data on patients whose sinus problems continue even after a surgical intervention. Other groups are examining the sinus microbiome of patients at the time of surgery.