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Preprints, Working Papers, ... Year : 2023

A gut meta-interactome map reveals modulation of human immunity by microbiome effectors

Veronika Young
Bushra Dohai
Thomas Hitch
Patrick Hyden
  • Function : Author
Benjamin Weller
Niels van Heusden
  • Function : Author
Deeya Saha
  • Function : Author
Jaime Fernandez Macgregor
  • Function : Author
Sibusiso Maseko
Chung-Wen Lin
Mégane Boujeant
  • Function : Author
Sébastien Choteau
  • Function : Author
Franziska Ober
  • Function : Author
Patrick Schwehn
  • Function : Author
Simin Rothballer
  • Function : Author
Melina Altmann
  • Function : Author
Stefan Altmann
Alexandra Strobel
  • Function : Author
Michael Rothballer
Marie Tofaute
Matthias Heinig
Thomas Clavel
Jean-Claude Twizere
Marianne Boes
Daniel Krappmann
Claudia Falter
Thomas Rattei
Pascal Falter-Braun

Abstract

SUMMARY The molecular mechanisms by which the gut microbiome influences human health remain largely unknown. Pseudomonadota is the third most abundant phylum in normal gut microbiomes. Several pathogens in this phylum can inject so-called virulence effector proteins into host cells. We report the identification of intact type 3 secretion systems (T3SS) in 5 - 20% of commensal Pseudomonadota in normal human gut microbiomes. To understand their functions, we experimentally generated a high-quality protein-protein meta-interactome map consisting of 1,263 interactions between 289 bacterial effectors and 430 human proteins. Effector targets are enriched for metabolic and immune functions and for genetic variation of microbiome-influenced traits including autoimmune diseases. We demonstrate that effectors modulate NF-κB signaling, cytokine secretion, and adhesion molecule expression. Finally, effectors are enriched in metagenomes of Crohn’s disease, but not ulcerative colitis patients pointing toward complex contributions to the etiology of inflammatory bowel diseases. Our results suggest that effector-host protein interactions are an important regulatory layer by which the microbiome impacts human health.
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hal-04240263 , version 1 (13-10-2023)

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Attribution - NonCommercial - NoDerivatives

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Veronika Young, Bushra Dohai, Thomas Hitch, Patrick Hyden, Benjamin Weller, et al.. A gut meta-interactome map reveals modulation of human immunity by microbiome effectors. 2023. ⟨hal-04240263⟩
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