Identification of trypsin-degrading commensals in the large intestine

• Published in: Nature (London) Vol. 609; no. 7927; pp. 582 - 589
• Main Authors: 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 15.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 101/28; 13/1; 42/41; 631/250/347; 631/326/2565/2134; 64/60; 82/16; 82/29; 82/58; 82/83; Antibiotics; Autolysis; Citrobacter; Colonization; Commensals; Coronaviruses; Degradation; Diarrhea; Enzymes; Hepatitis; Homeostasis; Humanities and Social Sciences; Immunoglobulin A; Infections; Intestinal microflora; Intestine; Large intestine; Microbiomes; Microbiota; multidisciplinary; Pathogens; Polysaccharides; Proteins; Science; Science (multidisciplinary); Severe acute respiratory syndrome coronavirus 2; Trypsin; Viral diseases
• ISSN: 0028-0836; 1476-4687; 1476-4687
• DOI: 10.1038/s41586-022-05181-3

Increased levels of proteases, such as trypsin, in the distal intestine have been implicated in intestinal pathological conditions 1 – 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 cells 4 , 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. Colonization of trypsin-degrading commensal bacteria may contribute to the maintenance of intestinal homeostasis and protection against pathogen infection in humans and mice.