[Epistemic status: I am not a doctor and this is not medical advice, but there are two RCTs supporting this. Also I talk about poop.]
Like many others, I've been excitedly reading about semaglutide over the last few days. For someone like Stephan Guyenet, author or The Hungry Brain, it seems like a vindication of the weight regulation model via the brain and signaling hormones (what he calls the lipostat) and he seems excited about it.
But let me tell you a quick story. I got a stomach bug, probably something like traveler's diarrhea, a few months ago. I tried several things to help fix it, and at one point was at Whole Foods starring down the wall of probiotics.
I Googled "probiotics by level of evidence" and one of the first page results was the Clinical Guide to Probiotic Products Available in USA. No one else was in the aisle, so I took some time to skim it. It has a table of probiotic supplements showing the level of evidence for each (the familiar Level I, Level II and Level III) related to what they're intended to treat and the strains of probiotics in the supplement.
That whole list was surprising and worth reading in terms of evidence for probiotics to support mood and affect, lower LDL-C, etc. But looking specifically at weight management, all of the probiotics for it contain some form of B. animalis ssp. lactis in the dose around 10 billion per capsule per day or higher. There's two Level I (RCT-level studies) showing it's effectiveness for that purpose. It's also in Activia yoghurt but the dose is much smaller.
I was and remain skeptical, but nothing sets off my evidence evaluation alarm bells. The first of the two, a 2016 study, was published in EBioMedicine and is in the 89th percentile in General Biochemistry, Genetics and Molecular Biology. The second is from 2020 and is in Scientific Reports which is in the 93rd percentile under the category Multidisciplinary. Neither of them are on Beall's List. The results aren't as spectacular as semaglutide where people saw a 17.4% reduction in weight over 68 weeks. But they are pretty good. In the 2016 study here was a 4.5% reduction over 6 months (in the best case where it was given with additional dietary fiber).
From the 2020 study.
In the 2020 study, this amounts to a 1.5% weight reduction in 6 months. Neither of these are completely fair as the semaglutide trial was over 15 months.
There is perhaps an advantage to the probiotic approach in the sense of the precautionary principle. Semaglutide is new. B. animalis subsp. lactis is "the world’s most documented probiotic Bifidobacterium" and was found in dairy cultures. People have been eating Activia for a long time now without weird side-effects. So we have more of a history with it and reason to believe it's safer.
So... all of this has just left me wondering why it hasn't been as much of a part of the weight loss discussion? Maybe there's something I'm missing?