A Study of Short-Chain Fatty Acids During the Canalicular and Early Saccular Phases of Fetal Lung Development and Childhood Asthma

Background: Emerging literature indicates that the microbiome and its byproducts, such as short-chain fatty acids (SCFAs), play an important role in childhood diseases such as allergies and asthma. Specifically, there is evidence suggesting that SCFAs play a critical role in fetal immunoprogramming during the late saccular phase of fetal lung development. An increase in acetate during the late saccular phase is known to play a critical role in inhibiting histone deacetylases (HDACs), resulting in a cascade of events, including Treg immune regulation, involved in fetal immunoprogramming, and reduction in the asthma phenotype. However, it is not known whether changes in SCFA levels, especially acetate, occurred during the canalicular or early saccular phase among pregnant women whose children did not develop asthma.

Methods: In this research, we investigated this question using plasma samples obtained from mothers during the 20th and 28th weeks of pregnancy. Mothers whose children developed asthma were categorized as cases, while those whose children did not were categorized as controls. The specimens were assayed for a panel of SCFAs consisting of acetate, propionate, butyrate, valerate, isobutyrate, and isovalerate.

Results: The resulting data indicated no significant differences between the cases and controls, either at week 20 or week 28, in any of the SCFAs measured, despite the vascularization during these phases.

Conclusions: We did not find differences in measured SCFAs at week 20 or at week 28. A larger prospective study covering multiple time points is necessary to confirm the findings of this preliminary study. Such a study, together with the published literature regarding later time points, may help discover critical windows during pregnancy when simple manipulation of diet will result in healthier outcomes for infants.