Infants born under 1500 grams have an increased incidence of necrotizing enterocolitis in the ileum and the colon which is a life-threatening intestinal necrosis. This is in part due to excessive inflammation in the immature intestine to colonizing bacteria because of an immature innate immune response. Breastmilk complex carbohydrates create metabolites of colonizing bacteria in the form of short-chain fatty acids (SCFAs). We studied the effect of breastmilk metabolites, SCFAs, on immature intestine with regard to anti-inflammatory effects. This showed that acetate, propionate and butyrate were all anti-inflammatory to an IL-1β inflammatory stimulus. In this study, to further define the mechanism of anti-inflammation, we created transcription profiles of RNA from immature human enterocytes after exposure to butyrate with and without an IL-1β inflammatory stimulus. We demonstrated that butyrate stimulates an increase in tight-junction and mucus genes and if we inhibit these genes the anti-inflammatory effect is partially lost. SCFAs, products of microbial metabolism of complex carbohydrates of breastmilk oligosaccharides, have been found with this study to induce an anti-IL-1β response that is associated with an upregulation of tight junctions and mucus genes in epithelial cells (H4 cells). These studies suggest that breastmilk in conjunction with probiotics can reduce excessive inflammation with metabolites that are anti-inflammatory and stimulate an increase in the mucosal barrier.

中文翻译：

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短链脂肪酸丁酸酯是一种母乳代谢物，可增强未成熟的肠道屏障功能基因对体外和体内炎症的反应


出生体重在 1500 克以下的婴儿回肠和结肠坏死性小肠结肠炎的发病率较高，这是一种危及生命的肠坏死。这部分是由于不成熟的先天免疫反应导致未成熟的肠道内细菌过度炎症所致。母乳复合碳水化合物以短链脂肪酸 (SCFA) 的形式产生定植细菌的代谢产物。我们研究了母乳代谢物 SCFA 对未成熟肠道的抗炎作用。这表明乙酸盐、丙酸盐和丁酸盐均对 IL-1β 炎症刺激物具有抗炎作用。在这项研究中，为了进一步明确抗炎机制，我们创建了未成熟人肠细胞暴露于丁酸盐（有或没有 IL-1β 炎症刺激物）后的 RNA 转录谱。我们证明丁酸盐会刺激紧密连接和粘液基因的增加，如果我们抑制这些基因，抗炎作用就会部分丧失。这项研究发现，SCFA 是母乳寡糖复合碳水化合物的微生物代谢产物，可诱导抗 IL-1β 反应，该反应与上皮细胞（H4 细胞）中紧密连接和粘液基因的上调有关。这些研究表明，母乳与益生菌结合可以通过抗炎代谢物减少过度炎症，并刺激粘膜屏障的增加。