小柯机器人

日本庆应大学医学院Kenya Honda等研究人员合作鉴定出大肠中胰蛋白酶降解的共生菌。该项研究成果于2022年9月7日在线发表在《自然》杂志上。

研究人员表明，从健康人的粪便微生物组中分离出来的帕拉普氏菌菌株是强有力的胰蛋白酶降解共生菌。从机制上讲，帕拉普氏菌通过依赖IX型分泌系统的多糖锚定蛋白将胰蛋白酶招募到细菌表面，从而促进胰蛋白酶自溶。帕拉普氏菌定植可以保护IgA不被胰蛋白酶降解，并增强口服疫苗对鼠柠檬杆菌的有效性。此外，帕拉普氏菌定植抑制了小鼠肝炎病毒-2的致命感染，这种小鼠冠状病毒依赖胰蛋白酶和胰蛋白酶样蛋白酶进入宿主细胞。一致的是，肠道微生物组中参与胰蛋白酶降解潜在基因的携带与SARS-CoV-2感染患者的腹泻严重程度降低有关。因此，胰蛋白酶降解的共生菌定植可能有助于维持肠道的平衡和保护病原体感染。

据介绍，肠道远端蛋白酶（如胰蛋白酶）水平的增加与肠道病理状况有关联。然而，肠腔内蛋白酶调节的参与者和机制仍不清楚。

附：英文原文

Title: Identification of trypsin-degrading commensals in the large intestine

Author: Li, Youxian, Watanabe, Eiichiro, Kawashima, Yusuke, Plichta, Damian R., Wang, Zhujun, Ujike, Makoto, Ang, Qi Yan, Wu, Runrun, Furuichi, Munehiro, Takeshita, Kozue, Yoshida, Koji, Nishiyama, Keita, Kearney, Sean M., Suda, Wataru, Hattori, Masahira, Sasajima, Satoshi, Matsunaga, Takahiro, Zhang, Xiaoxi, Watanabe, Kazuto, Fujishiro, Jun, Norman, Jason M., Olle, Bernat, Matsuyama, Shutoku, Namkoong, Ho, Uwamino, Yoshifumi, Ishii, Makoto, Fukunaga, Koichi, Hasegawa, Naoki, Ohara, Osamu, Xavier, Ramnik J., Atarashi, Koji, Honda, Kenya

Issue&Volume: 2022-09-07

Abstract: Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1,2,3. However, the players and mechanisms that underlie protease regulation in the intestinal lumen have remained unclear. Here we show that Paraprevotella strains isolated from the faecal microbiome of healthy human donors are potent trypsin-degrading commensals. Mechanistically, Paraprevotella recruit trypsin to the bacterial surface through type IX secretion system-dependent polysaccharide-anchoring proteins to promote trypsin autolysis. Paraprevotella colonization protects IgA from trypsin degradation and enhances the effectiveness of oral vaccines against Citrobacter rodentium. Moreover, Paraprevotella colonization inhibits lethal infection with murine hepatitis virus-2, a mouse coronavirus that is dependent on trypsin and trypsin-like proteases for entry into host cells4,5. Consistently, carriage of putative genes involved in trypsin degradation in the gut microbiome was associated with reduced severity of diarrhoea in patients with SARS-CoV-2 infection. Thus, trypsin-degrading commensal colonization may contribute to the maintenance of intestinal homeostasis and protection from pathogen infection.

DOI: 10.1038/s41586-022-05181-3

Source: https://www.nature.com/articles/s41586-022-05181-3

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