Identification of trypsin-degrading commensals in the large intestine

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

Research output: Contribution to journalArticlepeer-review

Abstract

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions1–3. 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.

Original languageEnglish
JournalNature
DOIs
Publication statusAccepted/In press - 2022

ASJC Scopus subject areas

  • General

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