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Sci Rep. 2017 Jul 31;7(1):6955. doi: 10.1038/s41598-017-07196-7.

Aggravation of collagen-induced arthritis by orally administered Porphyromonas gingivalis through modulation of the gut microbiota and gut immune system.

Author information

1
Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
2
Division of Periodontology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
3
Research Centre for Advanced Oral Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
4
Laboratory for Intestinal Ecosystem, RIKEN Centre for Integrative Medical Sciences (IMS), Yokohama, Japan.
5
Division of Dental Educational Research Development, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
6
Division of Orthopedic Surgery, Department of Regenerative and Transplant Medicine, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
7
Institute for Integrated Cell-Materials Science (WPI-iCeMS), Kyoto University, Sakyo, Kyoto, Japan.
8
Laboratory for Integrative Omics, RIKEN Quantitative Biology Center (QBiC), Osaka, Japan.
9
Division of Cariology, Operative Dentistry and Endodontics, Department of Oral Health Science, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
10
Research Unit for Oral-Systemic Connection, Division of Oral Science for Health Promotion, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan. kaz@dent.niigata-u.ac.jp.

Abstract

Porhyromonas gingivalis, a causative bacterium of periodontitis, is implicated in the etiology of rheumatoid arthritis (RA), mainly because of expressing peptidyl arginine deiminase (PAD) that generates RA-related autoantigens. However, compared with other periodontopathic bacteria, the precise role of P. gingivalis in RA is largely unknown. We found that orally administered P. gingivalis changed the gut microbiome with concomitant elevation of serum endotoxin and inflammatory markers, and impairment of the gut barrier function. Based on findings showing a relationship between gut microbiota and RA, we investigated whether the change of gut microbiota induced by P. gingivalis and Prevotella intermedia, another periodontopathic bacterium without PAD, is associated with collagen-induced arthritis (CIA). DBA/1J mice were orally administered with or without bacteria followed by induction of CIA. P. gingivalis, but not P. intermedia, administration significantly aggravated arthritis with increased interleukin-17 levels in sera and culture supernatants, increased Th17 cell proportions among mesenteric lymphocytes, and a significant change in the gut microbiome. However, P. gingivalis administration did not elevate the level of anti-citrullinated protein antibody. These results suggest a unique role of P. gingivalis in the link between periodontitis and RA by affecting the gut immune system and the gut microbiota composition.

PMID:
28761156
PMCID:
PMC5537233
DOI:
10.1038/s41598-017-07196-7
[Indexed for MEDLINE]
Free PMC Article

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