Anti‐inflammatory actions of acetate, propionate, and butyrate in fetal mouse jejunum cultures ex vivo and immature small intestinal cells in vitro

Necrotizing enterocolitis (NEC) is an intestinal disease that frequently occurs in premature infants. Presently, there is no effective therapy for NEC. Therefore, the key to reduce the incidence rate of NEC is to take effective intervention measures as early as possible. Short‐chain fatty acids (SCFAs) (acetate, propionate, and butyrate), the principal terminal products of enterobacteria fermentation, play anti‐inflammatory actions in mature intestinal cells. However, few studies focus on their roles in immature intestine. Here, we evaluated the anti‐inflammatory actions of SCFAs ex vivo with ICR fetal mouse jejunum cultures and explored the potential anti‐inflammatory regulators through RNA‐seq and then verified them in vitro with human fetal small intestinal epithelial FHs 74 Int cells. In this study, we found that acetate, propionate, and butyrate decreased IL‐1β‐induced production of CXCL2 ex vivo and IL‐8 and IL‐6 in vitro significantly (p < .05). Furthermore, the inhibitors of NF‐κB p65, JNK1/2, and ERK1/2 pathways, which were selected from RNA‐seq and depressed by SCFAs, also significantly decreased IL‐8 and IL‐6 productions induced by IL‐1β (p < .05). Therefore, our results showed that acetate, propionate, and butyrate ameliorated the fetal small intestine inflammatory response induced by IL‐1β through inhibiting ERK1/2 pathway; NF‐κB p65, JNK1/2, and ERK1/2 pathways; or NF‐κB p65 and ERK1/2 pathways, respectively. These findings suggested that SCFAs may be a new therapy agent for NEC.