3.4. Butyrate-induced changes in the integrity of gut and BBB
We studied the effect of sodium butyrate (NaB) on the gut epithelium and BBB (Fig. 7). When NaB was applied to the gut barrier module, the integrity of both gut barrier and BBB was improved, judging from the increase in the measured TEER values. hBMECs mono-cultured in transwell was directly exposed to NaB and showed increased TEER value. Given these results, we speculate that NaB treated in the gut exerted a positive effect on the brain endothelium. Butyrate is known to enhance barrier function of gut epithelium and thought to be important in maintaining the gut health (Bedford & Gong, 2018; L. Peng, He, Chen, Holzman, & Lin, 2007). Also, it has been reported that butyrate affect BBB permeability and exerts neuroprotective effect by restoring the BBB (Braniste et al., 2014; Li et al., 2016). Preserving and restoring BBB integrity presents a primary target for developing neuroprotective strategies (Parker et al., 2020), suggesting this short-chain fatty acids (SCFA) can be a drug candidate targeting GBA. Our study has demonstrated that the modular GBA chip can recapitulate the beneficial effect of NaB via interaction with gut epithelium and BBB.