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Identification of trypsin-degrading commensals in the large intestine.
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.
  • Li Y; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Watanabe E; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Kawashima Y; Institute for Cancer Research, Faculty of Medicine, University of Oslo, Oslo, Norway.
  • Plichta DR; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Wang Z; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Ujike M; Department of Pediatric Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
  • Ang QY; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Wu R; Department of Applied Genomics, Kazusa DNA Research Institute, Kisarazu, Japan.
  • Furuichi M; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Takeshita K; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Yoshida K; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Nishiyama K; Faculty of Veterinary Medicine, Nippon Veterinary and Life Science University, Tokyo, Japan.
  • Kearney SM; Infectious Disease and Microbiome Program, Broad Institute of MIT and Harvard, Cambridge, MA, USA.
  • Suda W; Interdisciplinary Life Science-PULSe, Purdue University, West Lafayette, IN, USA.
  • Hattori M; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Sasajima S; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Matsunaga T; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Zhang X; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Watanabe K; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Fujishiro J; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Norman JM; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Olle B; Cooperative Major in Advanced Health Science, Graduate School of Advanced Science and Engineering, Waseda University, Tokyo, Japan.
  • Matsuyama S; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Namkoong H; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Uwamino Y; RIKEN Center for Integrative Medical Sciences, Yokohama, Japan.
  • Ishii M; Department of Microbiology and Immunology, Keio University School of Medicine, Tokyo, Japan.
  • Fukunaga K; JSR-Keio University Medical and Chemical Innovation Center, Keio University School of Medicine, Tokyo, Japan.
  • Hasegawa N; Department of Pediatric Surgery, Faculty of Medicine, The University of Tokyo, Tokyo, Japan.
  • Ohara O; Vedanta Biosciences, Cambridge, MA, USA.
  • Xavier RJ; Vedanta Biosciences, Cambridge, MA, USA.
  • Atarashi K; Department of Virology III, National Institute of Infectious Diseases, Tokyo, Japan.
  • Honda K; Department of Infectious Diseases, Keio University School of Medicine, Tokyo, Japan.
Nature ; 609(7927): 582-589, 2022 09.
Article in English | MEDLINE | ID: covidwho-2016756
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Symbiosis / Trypsin / Gastrointestinal Microbiome / Intestine, Large Type of study: Prognostic study Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Journal: Nature Year: 2022 Document Type: Article Affiliation country: S41586-022-05181-3

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Symbiosis / Trypsin / Gastrointestinal Microbiome / Intestine, Large Type of study: Prognostic study Topics: Long Covid / Vaccines Limits: Animals / Humans Language: English Journal: Nature Year: 2022 Document Type: Article Affiliation country: S41586-022-05181-3