I found the description of the many interventions applied to the mice a bit confronting, but setting that aside:
I thought this was an interesting paper and the authors had thought about possible issues with their studies. They did a lot, and it would take me more time than I think I could be bothered to devote to it to get even a reasonable understanding of it all. My biggest concern is that, in doing so much, it was perhaps easy for the researchers to discard the things tried that didn't show an effect and just highlight the things that did.
They noted that the doses of mould exposure applied were higher than what a human would typically be exposed to, but also noted that in real life situations there would be nanoparticles of mould debris that might be inhaled deeper, as well as a mixture of contaminants.
They concluded that both toxic mould and non-toxic parts of mould (of one particular mould species) do have an effect on the innate immune system. And while of course more replications are needed and some of their conclusions, especially about behavioural impacts, are a bit questionable, that seems a reasonable overall conclusion to draw.
But lots of everyday things can potentially have a negative impact on the innate immune system; perhaps the innate immune system actually needs some challenges. So I guess the question is, how big of a problem is mould exposure in real life situations at real life dosages? Is it just the black mould species, or are other moulds a problem?
The authors note this:
Furthermore, roughly 25% of Americans carry major histocompatibility complex gene variants that make them susceptible to long-term inflammation following mold exposure, including the initiation of autoimmune problems and changes in brain structure/function (see Table 3 in Shoemaker et al., 2017).
I'd be interested to know more about this genetic susceptibility idea - does it have much to support it?
However, mold exposure, both toxic and nontoxic, must be considered another factor, like pesticide exposure or smoking, that can add to an individual’s burden of inflammation with possible serious consequences for health and behavior.
That way of thinking about it makes sense to me - mould exposure typically being just another factor influencing an immune response. So it might fit with the idea of multiple small hits, mould exposure together with a viral or bacterial exposure at a time when the body is vulnerable perhaps because of physical exertion (or a single major hit like Ebola), that result in a level of immune response sufficiently high to trigger ME/CFS.
