[Herodotus38]

In your opinion, what is the best study that shows direct evidence that changes in gut flora can change health outcomes (preferably something that is a randomized control study). The only area I feel comfortable that good data exists is in the setting of fecal transplants for refractory clostridioides difficile infection. Thanks.

[wdwvt1]

I think you hit it on the head - the C. diff stuff is good and will meet FDA criteria soon (the phase III data from ECOSPOR was good: https://www.clinicaltrials.gov/ct2/show/NCT03183128).

In general we only have mouse or other animal data for other indications.

There are retrospective analyses of patient cohorts receiving anti-PD1 or anti-CTLA4 therapies which have identified certain microbiome states as supportive of those therapies. I believe that these are probably real effects, though I don't think the particular microbes matter - instead I think it's the metabolites they produce and how those influence resting immune state (https://www.science.org/doi/10.1126/science.abf3363 - but you can find many more).

A paper I really like shows that a specific protein from a common gut microbe (Akkermansia muciniphila) confers resistance to diet induced weight gain, insulin insensitivity, etc. (https://www.nature.com/articles/nm.4236).

In general, I think the majority of microbiome work has been associational and demonstrative of the kind of hypothesis-free science that is prone to all sorts of statistical artifacts and misaligend incentives between truth-finding and paper publishing (garden of forking paths, file-drawer effect, etc. etc.)