Have you looked at any fungal diversity? I had a Candida overgrowth issue pre-sema and anecdotally it seems better. Wondering if ITS sequencing would show anything interesting.
I haven't done ITS sequencing — it's on my list though. The mycobiome is chronically understudied in metabolic disease. There IS some evidence that GLP-1 signaling modulates intestinal Candida colonization via effects on mucosal immunity, but it's very preliminary (mostly in vitro). If I do run ITS panels I'll absolutely post the results here.
One thing I'd love to see studied: do probiotics during the initial titration phase reduce GI side effects by buffering that diversity dip you saw at month 3? Like, could we pre-load with specific strains to smooth the transition?
I started taking Seed DS-01 about 2 months before sema and my GI side effects were extremely mild. Obviously anecdotal and I have no baseline comparison, but it's an interesting thought.
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That's actually a fantastic hypothesis. You could design a simple RCT: semaglutide + multi-strain probiotic vs. semaglutide + placebo, primary endpoint being GI symptom severity (maybe using the GSRS questionnaire) during the first 16 weeks of titration, with 16S at baseline/week 8/week 16 as a secondary endpoint.
If any pharma or supplement companies are lurking here, you're welcome for the free study design 😂
Seriously though, I think the microbiome story with GLP-1 agonists is going to be one of the big research areas in the next 5 years. The gut-brain axis, the gut-metabolic axis — semaglutide is sitting right at the intersection of all of it.