Nishiyama Hiroki, Nagai Tomoyuki, Kudo Masatoshi, Okazaki Yoshihisa, Azuma Yoshinao, Watanabe Tomohiro, Goto Susumu, Ogata Hiroyuki, Sakurai Toshiharu
Institute for Chemical Research, Kyoto University, Gokasho, Uji, Kyoto 611-0011, Japan.
Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, 377-2 Ohno-Higashi, Osaka-Sayama, Osaka 589-8511, Japan.
Biochem Biophys Res Commun. 2018 Jan 1;495(1):273-279. doi: 10.1016/j.bbrc.2017.10.130. Epub 2017 Oct 26.
Although pancreatic enzyme replacement therapy (PERT) is effective in the alleviation of pancreatic exocrine insufficiency (PEI)-related symptoms in patients with chronic pancreatitis, its mechanism of action is poorly understood. Recent studies suggest that the intestinal microbiota is associated with the pathogenesis of chronic pancreatitis. Therefore, we hypothesized that PERT exerts its effect by modifying the intestinal microbiota in addition to its presumed role in promoting fat and protein absorption. To explore the mechanism of action of PERT, we analyzed the intestinal microbiotas of two groups of mice treated with either pancrelipase or tap water by using 16S rRNA amplicon sequencing. The results revealed that the bacterial compositions of the pancrelipase-treated mice were significantly different from those of the control samples. Akkermansia muciniphila, a key beneficial bacterium in the intestinal tract, showed a higher relative abundance in the pancrelipase-treated samples than in the control samples. Lactobacillus reuteri, a widely used probiotic bacterium known to relieve intestinal inflammation, also showed a higher relative abundance in the pancrelipase-treated samples. These results suggested that PERT induces the colonization of beneficial bacteria, thereby contributing to the attenuation of PEI-associated symptoms in addition to improvement of the nutritional state.
尽管胰酶替代疗法（PERT）可有效缓解慢性胰腺炎患者的胰腺外分泌功能不全（PEI）相关症状，但其作用机制仍知之甚少。最近的研究表明，肠道微生物群与慢性胰腺炎的发病机制有关。因此，我们推测PERT除了在促进脂肪和蛋白质吸收方面的假定作用外，还通过改变肠道微生物群发挥其作用。为了探究PERT的作用机制，我们通过16S rRNA扩增子测序分析了两组分别用胰酶或自来水处理的小鼠的肠道微生物群。结果显示，胰酶处理组小鼠的细菌组成与对照样本有显著差异。肠道中的关键有益菌嗜黏蛋白阿克曼氏菌在胰酶处理组样本中的相对丰度高于对照样本。罗伊氏乳杆菌是一种广泛使用的已知可缓解肠道炎症的益生菌，在胰酶处理组样本中也显示出较高的相对丰度。这些结果表明，PERT可诱导有益菌的定殖，从而除改善营养状态外，还有助于减轻PEI相关症状。
