Identification of trypsin-degrading commensals in the large intestine
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Abstract
Abstract 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.
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Host proteases such as trypsin are capable of degrading IgA, and microbial commensals such as Paraprevotella can prevent its degradation in the gut.
“Host proteases such as trypsin are capable of degrading IgA, and microbial commensals such as Paraprevotella can prevent its degradation in the gut.9”
From The emerging roles of bacterial proteases in intestinal diseases (2023) · cites this paper as [9]
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The emerging roles of bacterial proteases in intestinal diseases
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- Authors
- Li, Y., Watanabe, E., Kawashima, Y., Plichta, D. R., Wang, Z., Ujike, M., Ang, Q. Y., Wu, R., Furuichi, M., Takeshita, K., Yoshida, K., Nishiyama, K., Kearney, S. M., Suda, W., Hattori, M., Sasajima, S., Matsunaga, T., Zhang, X., Watanabe, K., Fujishiro, J., Norman, J. M., Olle, B., Matsuyama, S., Namkoong, H., Uwamino, Y., Ishii, M., Fukunaga, K., Hasegawa, N., Ohara, O., Xavier, R. J., Atarashi, K., & Honda, K.
- Affiliations
- University of Oslo (NO)
- Keio University (JP)
- Kazusa DNA Research Institute (JP)
- Broad Institute (US)
- Nippon Veterinary and Life Science University (JP)
- RIKEN Center for Integrative Medical Sciences (JP)
- Waseda University (JP)
- The University of Tokyo (JP)
- National Institute of Infectious Diseases (JP)
- Corresponding author
- Xavier, Ramnik J.
- Atarashi, Koji
- Honda, Kenya
- ORCID
- Li, Youxian
- Watanabe, Eiichiro
- Kawashima, Yusuke
- Plichta, Damian R.
- Ujike, Makoto
- Ang, Qi Yan
- Furuichi, Munehiro
- Yoshida, Koji
- Nishiyama, Keita
- Kearney, Sean M.
- Suda, Wataru
- Hattori, Masahira
- Zhang, Xiaoxi
- 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
- Venue
- Nature
- Published
- 2022-09-07
- Volume
- 609
- Issue
- 7927
- Pages
- 582-589
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- PMC
- PMC9477747
- OpenAlex
- W4294904666
- Cited by
- 106
- References
- 75
- Citations by year
- 2026: 25 · 2025: 38 · 2024: 29 · 2023: 14
- FWCI
- 6.61
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature (publishedVersion, cc-by)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- RePEc: Research Papers in Economics (submittedVersion, cc-by)
- NORA - Norwegian Open Research Archives (submittedVersion, cc-by)
- Funders
- Japan Agency for Medical Research and Development (JP21ae0121041, 20fk0108415h0001, JP20nk0101612,, 20gm0010003h0005, 20fk0108452h0001, JP20ek0210154)
- European Commission (HORIZON2020, COVID-19)
- Keio University
- Stand Up To Cancer (Convergence 3.1416, 3.1416)
- Japan Society for the Promotion of Science (JP20fk0108452, 20H05627, JP20fk0108415)
- RIKEN
- National Institute of Diabetes and Digestive and Kidney Diseases (P30DK043351)
- National Center for Complementary and Integrative Health (R01AT009708)
- H2020 Marie Skłodowska-Curie Actions (80113, HORIZON2020)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Endocrinology › Escherichia coli research studies
- Health Sciences › Dentistry › Periodontics › Oral microbiology and periodontitis research
- Keywords
- trypsin degradation, Paraprevotella, gut commensals, type IX secretion system, Citrobacter rodentium, intestinal homeostasis, gut microbiota, protease regulation
- MeSH terms
- Gastrointestinal Microbiome, COVID-19, SARS-CoV-2, Administration, Oral, Animals, Bacterial Vaccines, Diarrhea, Feces, Murine hepatitis virus, Humans, Immunoglobulin A, Intestine, Large, Symbiosis, Trypsin, Bacteroidetes, Citrobacter rodentium, Mice, Virus Internalization, Bacterial Secretion Systems, Proteolysis
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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