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.