Role of the Lower and Upper Intestine in the Production and Absorption of Gut Microbiota-Derived PUFA Metabolites

In vitro studies have suggested that isolated gut bacteria are able to metabolize PUFA into CLA (conjugated linoleic acids) and CLnA (conjugated linolenic acids). However, the bioavailability of fatty acid metabolites produced in vivo by the gut microbes remains to be studied. Therefore, we measured intestinal concentration and plasma accumulation of bacterial metabolites produced from dietary PUFA in mice, first injected with a lipoprotein lipase inhibitor, then force-fed with either sunflower oil (200 µl) rich in n-6 PUFA or linseed oil (200 µl) rich in n-3 PUFA. The greatest production of bacterial metabolites was observed in the caecum and colon, and at a much lesser extent in the jejunum and ileum. In the caecal content, CLA proportions were higher in sunflower oil force-fed mice whereas CLnA proportions were higher in linseed oil force-fed mice. The accumulation of the main metabolites (CLA cis-9,trans-11-18:2 and CLnA cis-9,trans-11,cis-15-18:3) in the caecal tissue was not associated with their increase in the plasma, therefore suggesting that, if endogenously produced CLA and CLnA have any biological role in host metabolism regulation, their effect would be confined at the intestinal level, where the microbiota is abundant.

体外实验研究表明，分离得到的肠道细菌可将多不饱和脂肪酸（Polyunsaturated Fatty Acids, PUFA）代谢为共轭亚油酸（conjugated linoleic acids, CLA）与共轭亚麻酸（conjugated linolenic acids, CLnA）。然而，肠道微生物在体内生成的脂肪酸代谢物的生物利用度仍有待研究。为此，本研究以小鼠为模型，测定了膳食来源多不饱和脂肪酸经肠道细菌生成的代谢物的肠道浓度与血浆蓄积量；实验小鼠先被注射脂蛋白脂酶抑制剂（lipoprotein lipase inhibitor），随后分别强饲富含n-6多不饱和脂肪酸的葵花籽油（200 µl）或富含n-3多不饱和脂肪酸的亚麻籽油（200 µl）。研究发现，肠道细菌代谢物的生成量在盲肠与结肠中最高，在空肠与回肠中则显著较低。在盲肠内容物中，经葵花籽油强饲的小鼠体内共轭亚油酸占比更高，而经亚麻籽油强饲的小鼠体内共轭亚麻酸占比更高。盲肠组织中主要代谢物（即共轭亚油酸cis-9,trans-11-18:2与共轭亚麻酸cis-9,trans-11,cis-15-18:3）的蓄积量与其血浆水平的升高并无关联，这提示：若内源性生成的共轭亚油酸与共轭亚麻酸对宿主代谢调控具有生物学功能，则其作用位点应局限于微生物群富集的肠道局部。