Lowering of large bowel butyrate levels in healthy populations is unlikely to be beneficial

We read, with interest, the recent paper by Ferrario et al. (1). In it the authors describe a study that examined the effects of a probiotic supplement on a number of fecal biomarkers, one of which was butyrate, in a group of healthy volunteers. This SCFA is an important end product of large bowel fiber fermentation and is attracting considerable attention for its potential to promote visceral function and protect against serious large bowel disease in the long term, e.g., colorectal cancer. The authors have cited our paper (2) in which we reported the wide variation in fecal butyrate levels that exists in humans. However, what was not pointed out from our study was that the butyrate levels of most individuals were increased through consumption of resistant starch and that for those individuals within the highest quartile of entry butyrate levels, the levels generally fell in response to the treatment. In the study by Ferrario et al., the probiotic treatment increased butyrate levels when entry levels were lowest (but in only 6 individuals) and decreased levels at higher entry levels (the majority of the participants). Meaningful comparisons with our study are confounded by their report of ∼10-fold higher stool SCFA levels than we and most others find. Furthermore, the method for SCFA analysis is not provided in the supplementary material as indicated in the text. A reliable picture of butyrate concentrations would enable an understanding of whether the 2 studies have a common tipping point regarding when levels begin to drop in response to treatments.