MICROBIOLOGIST/HEALTH RESEARCHERS ONLY: What is the main theory underlying SIBO/MCAS/CIRS etc.?
Brief background: I'm a mathematics researcher, and as a patient I've struggled for as long as I can remember with anxiety, OCD, and panic attacks (treated with escitalopram since I was 18, I'm now 32). For the past few years, however, I've found myself stuck in a cycle of health anxiety, largely driven by a combination of issues that I'm trying to understand in a coherent way: gastrointestinal symptoms, recurrent skin rashes, brain fog, decades of mold exposure in my parents house and so on.
Current state of my understanding (based on reading as many papers as I've been able to):
- SIBO appears to be a fairly controversial diagnosis. The actual "constellation" of bacteria inhabiting the relevant portion of the small intestine is still poorly characterized, current diagnostic tools (such as breath tests) have substantial false-positive rates, and treatments often fail to resolve patients symptoms.
- MCAS seems even more controversial. Biomarkers fluctuate considerably, and the diagnosis itself is largely one of exclusion, somewhat reminiscent of what unfortunately happens with IBS.
- CIRS (Chronic Inflammatory Response Syndrome) is perhaps the most eclectic of the three. It relies on a collection of laboratory findings (MSH, complement C4a, TGF-β1, nasal presence of MARCoNS, ecc.) that are interpreted in the context of indoor mold exposure, and proposes a treatment protocol (e.g., the Shoemaker protocol) that, at least from my perspective, feels closer to an empirically assembled recipe than to a well-established mechanistic framework.
What strikes me is that these three diagnostic categories share an enormous overlap in symptoms. That makes me wonder whether they are all attempting (perhaps imperfectly) to describe different manifestations of the same underlying biological process. Patients across these groups commonly report gastrointestinal symptoms (often associated with food reactions), skin problems, brain fog, fatigue, nutritional deficiencies and a wide variety of other systemic symptoms.
Browsing the various Reddit communities, anecdotal reports are everywhere. Some people claim dramatic improvements from specific diets, others rely heavily on antihistamines while others again follow elaborate protocols aimed at removing mycotoxins from the body.
Taken together, and considering the much more established scientific evidence supporting bidirectional communication between the gut and the brain, help me say it "the gut-brain axis", I can't help wondering whether an important missing piece of the puzzle may not be entirely "organic" in the traditional sense. By that I don't mean "it's all psychological," but rather that higher level regulatory processes (brain-gut interactions, stress responses, autonomic regulation, perception and so on) may play a much larger role than we currently understand. Obviously this opens a much broader discussion about the relationship between mind and body, free will and similar topics, but that's not really my focus here.
So, after this rather long preamble, here's the question I'd really like to ask, ideally to people who actually study these topics professionally and approach them through the scientific method:
What is your current view (whether personal, data-driven or theory-driven) of the biological process that could underlie this remarkably broad yet surprisingly consistent spectrum of symptoms reported by patients across SIBO, MCAS and CIRS communities?
I'm not looking for diagnostic advice or treatment recommendations. Rather, I'm interested in conceptual models. If you use specialized terminology, I'd really appreciate it if you could also explain the underlying biological mechanism in accessible language instead of simply linking to highly technical papers. Given the audience I'm hoping to reach, I don't think there's much risk of oversimplifying the science behind.
Thank you very much in advance.