LAUSR

We appreciate the comment and interests in our recent report. Citing a reference on renal clearance of radioactively labeled acetate, the authors questioned whether the acetate can be incorporated inside the cells as epigenetic markers due to its rapid metabolism. Aside from the different experimental settings in that reference and in our report, it is reasonable to believe that a continuous intake of acetate will likely increase body's acetate and its biochemical derivatives as absorption of even aminor quantitywill shift the equilibrium towards a higher cellular acetate over a long period of time [1,2]. Indeed, our experimental observations provide concrete evidence to support an increase of histone acetylation with consequent transcriptional regulation of miRNAs. Our report does not exclude other mechanistic processes regarding vinegar's anti-nephrolithiasis effect, although we have provided multitude experimental evidence to support epigenetic regulations as an underlyingmechanism for vinegar's efficacy. Beforewe explore a potential role of gut microbiome inmediating vinegar's impact for the kidney, we need to clarify several points raised by the authors. Although mature vinegar is the result of fermentation, there is undetectable living microbiome in the final vinegar due to sterilization at the end of manufacturing process [3]. Therefore, there is no rich microbiome in the vinegar, just the complex mixture of fermentation product, the identity of which is likely varied and undetermined with one component in common, acetic acid. This further suggests that this component is likely the cause of kidney stone reduction associated with vinegar consumption, indeed confirmed by our animal studies using acetic acid. As such, the oxalate degradation effect in semi-finished vinegar can not be transmitted to humans in the form of microbiome bymature