University of Oulu

Ottman N, Reunanen J, Meijerink M, Pietilä TE, Kainulainen V, Klievink J, et al. (2017) Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function. PLoS ONE 12(3): e0173004.

Pili-like proteins of Akkermansia muciniphila modulate host immune responses and gut barrier function

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Author: Ottman, Noora1,2,3; Reunanen, Justus4; Meijerink, Marjolein5,6;
Organizations: 1Laboratory of Microbiology, Wageningen University, Wageningen, The Netherlands
2Department of Biosciences, University of Helsinki, Helsinki, Finland
3Institute of Environmental Medicine, Karolinska Institutet, Stockholm, Sweden
4Cancer and Translational Medicine Research Unit, Biocenter Oulu and Faculty of Medicine, University of Oulu, Oulu, Finland
5Host-Microbe Interactomics, Animal Sciences, Wageningen University, Wageningen, The Netherlands
6Department Risk Analysis for Products in Development, TNO, Zeist, the Netherlands
7Department of Veterinary Biosciences, Faculty of Veterinary Medicine, University of Helsinki, Helsinki, Finland
8Pharmacology, Faculty of Medicine, University of Helsinki, Helsinki, Finland
9Department of Bacteriology and Immunology, and Research Programs Unit, Immunobiology, University of Helsinki, Helsinki, Finland
10Hematology Research Unit Helsinki, University of Helsinki and Department of Hematology, Helsinki University Hospital Comprehensive Cancer Center, Helsinki, Finland
11Helsinki University Central Hospital Laboratory Diagnostics, Helsinki, Finland
12 Laboratory of Biochemistry, Wageningen University, Wageningen, The Netherlands
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 1.2 MB)
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Language: English
Published: Public Library of Science, 2017
Publish Date: 2017-04-13


Gut barrier function is key in maintaining a balanced response between the host and its microbiome. The microbiota can modulate changes in gut barrier as well as metabolic and inflammatory responses. This highly complex system involves numerous microbiota-derived factors. The gut symbiont Akkermansia muciniphila is positively correlated with a lean phenotype, reduced body weight gain, amelioration of metabolic responses and restoration of gut barrier function by modulation of mucus layer thickness. However, the molecular mechanisms behind its metabolic and immunological regulatory properties are unexplored. Herein, we identify a highly abundant outer membrane pili-like protein of A. muciniphila MucT that is directly involved in immune regulation and enhancement of trans-epithelial resistance. The purified Amuc_1100 protein and enrichments containing all its associated proteins induced production of specific cytokines through activation of Toll-like receptor (TLR) 2 and TLR4. This mainly leads to high levels of IL-10 similar to those induced by the other beneficial immune suppressive microorganisms such as Faecalibacterium prausnitzii A2-165 and Lactobacillus plantarum WCFS1. Together these results indicate that outer membrane protein composition and particularly the newly identified highly abundant pili-like protein Amuc_1100 of A. muciniphila are involved in host immunological homeostasis at the gut mucosa, and improvement of gut barrier function.

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Series: PLoS one
ISSN: 1932-6203
ISSN-E: 1932-6203
ISSN-L: 1932-6203
Volume: 12
Issue: 3
Article number: e0173004
DOI: 10.1371/journal.pone.0173004
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by Advanced Research Grant 250172 (MicrobesInside) of the European Research Council ( to WMdV, the Gravity (SIAM) and Spinoza grants of the Netherlands Organization for Scientific Research (NWO, to WMdV, the European Community's Seventh Framework Programme (FP7/2007-2013, under grant agreement n°215553-2 to NO, and the Finland Academy of Sciences ( (138902 & 258439 to RS, 252803 to JR, 141130 to WMdV). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
Dataset Reference: All relevant data are within the paper and its Supporting Information files.
Copyright information: © 2017 Ottman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.