| Microbiome researcher here. Like many microbiome results - this paper has tantalizing evidence of a powerful and systemic effect, but extremely limited direct evidence. The primary experiment in the paper is the transfer of stool contents from old mice to young mice (and vice versa). The chemical complexity of stool is hard to overstate - it's one of the most chemically diverse environments known. While the microbes are ~75% of the weight of feces (and thus of the fecal transplant) there is a huge complement of other things including host-derived effector molecules, fungal, and viral components. Three things that I think are important to think about: 1) A critical experiment to determine that it is bacteria (or fungal/virus) per se and not a host effector would be the transfer of contents from aged germ-free control mice (mice without microbes of any type). The authors mention a transfer protocol that could be optimized for fungal commensals, but don't address the more important germ-free control. 2) It is hard to characterize individual immune metabolites/signals (e.g. IL-10, IL-6, etc.) as either good or bad. The context determines the effect and they show changes in at least 20 cytokines in Fig 3E. While they focus on IL-6 and TNF, it's not immediately clear those are necessarily a part of pathogenic inflammageing. LBP conversely, seems pretty hard to interpret as anything but evidence of barrier permeability and this result seems strong. 3) It's not clear how much of this effect would sustain over the long term. The amount of time between fecal transplant and mouse sacrifice/result generation was only 18 days. Experiments with such a short duration seem like they might capture an unrelated effect due to some other coincident factor. Overall, a well done paper with a lot of interesting things, but also reasons to be very skeptical of the magnitude of this effect. As usual, I will end with: you can dramatically improve your microbiome health (whatever that term actually means) by eating a high fiber diet like most humans did for most of evolutionary time. |