Meconium Influences Pulmonary Short-Chain Fatty Acid Concentration in Porcine Meconium Aspiration Model

The factors influencing meconium aspiration syndrome (MAS) severity remain poorly understood. In a piglet model of MAS, we hypothesized the respiratory microbiome would reflect the bacterial signature of meconium with short-chain fatty acid (SCFA) accumulation as a byproduct of bacterial fermentation. Cesarean section at approximately 115-day term was performed on two sows. Male (9) and female (3) piglets were delivered, instrumented, anesthetized, and randomized into a Control ( = 6) or MAS group ( = 6). MAS received a meconium slurry (3 mL/kg) aspiration injury. Experimental animals were monitored continuously, ventilated, and resuscitated for 24 h. BALF was collected for 16S microbiome sequencing and SCFA analysis by gas chromatography. Effects of SCFAs on A549 alveolar pulmonary epithelial in vitro cell viability and inflammation were assessed. The MAS group had significantly higher fluid and vasopressor requirements than the Control group ( < 0.05) though both groups developed lung injury. The meconium microbiome demonstrated a difference in genus proportions as compared with the BALF of the Control and MAS groups. The MAS group had a relative increase in propionic acid-forming bacteria and higher BALF concentrations of propionic acid (0.6 ± 0.2 mmol/kg) than the Control group (0.2 ± 0.2 mmol/kg; > 0.05). Propionic acid was associated with decreased pulmonary epithelial cell viability and an upregulated pro-inflammatory response. Meconium may host a microbiome with byproducts that interact with the pulmonary epithelium and influence lung injury severity in MAS.