Refractory diet-dependent changes in neural microstructure: Implications for microstructural endophenotypes of neurologic and psychiatric disease.

Alterations in gut microbiome populations via dietary manipulation have been shown to induce diet-dependent changes in white matter microstructure. The purpose of this study is to examine the durability of these diet-induced microstructural alterations. We implemented a crossover experimental design where post-weaned male rats were assigned to one of four experimental diets. Following the administration of experimental diets and again following crossover and resumption of a normal diet, brains were imaged ex-vivo with diffusion tensor imaging. Following standard image preprocessing, tract-based spatial statistics and region-of-interest measurements were then calculated for all diffusion tensor indices. Voxel-wise differences in FA were identified in the high fat diet group when compared to animals receiving a control diet. Following crossover, there were new voxel-wise changes in both FA and TR that do not correspond to the regions previously identified. Animals crossed over from the high fiber diet demonstrate widespread and global changes in the diffusion tensor that stand in stark contrast to the minimal changes identified before crossover. While no significant differences between any of the diffusion metrics were identified in the high protein group before crossover, statistically significant decreased RD values were observed following resumption of a normal diet. Diet-induced changes in neural microstructure are durable changes that are unrecoverable following the resumption of a normal diet. We further show that in certain experimental diets, resumption of a normal diet can lead to further marked and unanticipated changes in white matter microstructure.