While the mechanism of how gut microbiota affect behavior remains to be elucidated, we show here that repletion of the bacterial fermentation products the SCFAs reverses the antibiotic-induced behavioral phenotype (Fig. 5). Interestingly, several recent studies have shown that SCFAs are a key component in the microbiota regulation of brain function2432. While the mechanism of action of the SCFAs on cellular and behavioral function is not fully known there are several possibilities. Of the three main SCFAs produced in the gut (butyrate, propionate, acetate), two are known to be histone deacetylase inhibitors (HDACs)30. Changes in epigenetic histone acetylation are well characterized as playing a role in the behavioral responses to cocaine4546. Studies have shown that chronic administration of HDAC inhibitors reduces behavioral responding for cocaine454748. An important goal for future research will be to study the possibility that knockdown of the gut microbiota reduces production of SCFAs, which act as HDAC inhibitors leading to increased behavioral sensitivity to cocaine49.
