Plenty. For starters, whether the human brain even harbors commensals, i.e., healthy people’s brains containing microbes in the absence of overt or discernible sickness. If this were the case, we’d need to change what’s written in textbooks. In fact this would be a foundational change for immunology. Many if not most of our solid organs are considered microbe-free, i.e., that microbes colonize our GI tract, mucosal surfaces and skin, nothing else. If this weren’t true, if in fact solid organs also harbored their suite of commensals, albeit in much more restricted numbers compared to the GI tract, it would fundamentally alter our understanding of basic physiology, especially immunology. Immunology in particular rests on the notion that microbes are restricted to barriers and that leukocytes patrol all over our body to ensure they stay restricted to those barrier sites. This foundational piece would need to go out the window if solid organs like the brain harbored their share of commensal microbes.

In the case of the brain, we’d also have to reconsider our understanding of the Blood–brain barrier. One of the principal notions to explain the BBB is as a structural barrier for blood-borne infections. Need for such a barrier was invoked by the fact that our brain is encased inside the bony skull, i.e., a priori limited capacity for tolerating Inflammation. After all, heavy influx of cells and fluid is the essential hallmark of inflammation. Tissues swell as a result. Being encased by the skull, brain obviously has limited swelling capacity. Microbes residing in the brain as a matter of course? How’s that possible without triggering inflammation? And if it is, what’s different about such microbes and/or how they interact with the local tissues and immune system to preclude classic inflammation? These would be burning questions needing answers. And of course, changing what’s written in textbooks about the BBB’s function would also be on the agenda.

Theoretical considerations aside, what does the data say? Turns out not nothing and isn’t that grand! At least one study found that regardless of immune status, Alphaproteobacteria appear to be major commensals present in human brain (Branton, William G., et al. “Brain microbial populations in HIV/AIDS: α-proteobacteria predominate independent of host immune status.” PloS one 8.1 (2013): e54673. Brain Microbial Populations in HIV/AIDS: α-Proteobacteria Predominate Independent of Host Immune Status). This is just one study. One small study of 4 controls and 4 HIV-infected individuals. Though well controlled to rule out trivial explanations such as blood cell contamination of sampled brain tissue or lab contamination, one small study is far from anything to perturb textbooks or their authors/editors. If other, larger studies found similar findings, a big if, then we’d really have something to talk about, in fact talk until the cows come home.