Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.

<h4>Objectives</h4>The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to...

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Main Authors: Shunya Motosugi, Naoki Takahashi, Shuhei Mineo, Keisuke Sato, Takahiro Tsuzuno, Yukari Aoki-Nonaka, Nao Nakajima, Kazuya Takahashi, Hiroki Sato, Haruna Miyazawa, Koji Taniguchi, Shuji Terai, Koichi Tabeta
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2025-01-01
Series:PLoS ONE
Online Access:https://doi.org/10.1371/journal.pone.0320383
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author Shunya Motosugi
Naoki Takahashi
Shuhei Mineo
Keisuke Sato
Takahiro Tsuzuno
Yukari Aoki-Nonaka
Nao Nakajima
Kazuya Takahashi
Hiroki Sato
Haruna Miyazawa
Koji Taniguchi
Shuji Terai
Koichi Tabeta
author_facet Shunya Motosugi
Naoki Takahashi
Shuhei Mineo
Keisuke Sato
Takahiro Tsuzuno
Yukari Aoki-Nonaka
Nao Nakajima
Kazuya Takahashi
Hiroki Sato
Haruna Miyazawa
Koji Taniguchi
Shuji Terai
Koichi Tabeta
author_sort Shunya Motosugi
collection DOAJ
description <h4>Objectives</h4>The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms.<h4>Methods</h4>In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development.<h4>Results</h4>The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity.<h4>Conclusion</h4>P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.
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spelling doaj-art-556312aa8fb249f0ae4fc230060aeb482025-08-20T03:07:21ZengPublic Library of Science (PLoS)PLoS ONE1932-62032025-01-01203e032038310.1371/journal.pone.0320383Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.Shunya MotosugiNaoki TakahashiShuhei MineoKeisuke SatoTakahiro TsuzunoYukari Aoki-NonakaNao NakajimaKazuya TakahashiHiroki SatoHaruna MiyazawaKoji TaniguchiShuji TeraiKoichi Tabeta<h4>Objectives</h4>The oral-gut axis is believed to play a role in the pathogenesis of colorectal cancer (CRC). Previous studies have demonstrated the transmission of oral microbiota to the gut, disrupting gut microbial balance and creating a protumorigenic microenvironment conducive to CRC progression. Fusobacterium nucleatum is a putative periodontal pathogen recognized as a specific bacterium that promotes CRC development. However, the possible involvement of other periodontal pathogens in CRC is poorly understood. This study aimed to explore the effects of ingested periodontal pathogens on experimental CRC in mice and elucidate the underlying mechanisms.<h4>Methods</h4>In this study, experimental colitis-induced CRC mouse models were used. The mice were orally administered periodontal pathogens (Porphyromonas gingivalis and Prevotella intermedia) three times a week during the experimental period. The CRC severity between the P. gingivalis-treated and P. intermedia-treated groups was compared. Lumen-associated microbiota (LAM) and mucosa-associated microbiota (MAM) were analyzed in both mouse and human samples. In vitro studies were conducted using intestinal epithelial cells to explore the possible mechanisms by which the periodontal pathogens affect the CRC development.<h4>Results</h4>The P. gingivalis-treated group exhibited significantly increased CRC severity compared to the other groups among azoxymethane/dextran sodium sulfate (AOM/DSS)-induced mouse models. The LAM and MAM exhibited distinct bacterial compositions, and P. gingivalis was enriched more in MAM than in LAM. In vitro adhesion assays revealed that P. gingivalis had higher adhesive capacity to intestinal epithelial cells than P. intermedia and indicated the possible involvement of gingipains in such a capacity.<h4>Conclusion</h4>P. gingivalis is enriched in MAM, and its subsequent adhesion to intestinal epithelial cells is potentially involved in the progression of CRC.https://doi.org/10.1371/journal.pone.0320383
spellingShingle Shunya Motosugi
Naoki Takahashi
Shuhei Mineo
Keisuke Sato
Takahiro Tsuzuno
Yukari Aoki-Nonaka
Nao Nakajima
Kazuya Takahashi
Hiroki Sato
Haruna Miyazawa
Koji Taniguchi
Shuji Terai
Koichi Tabeta
Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
PLoS ONE
title Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
title_full Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
title_fullStr Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
title_full_unstemmed Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
title_short Enrichment of Porphyromonas gingivalis in colonic mucosa-associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis: Insights from in vivo and clinical studies.
title_sort enrichment of porphyromonas gingivalis in colonic mucosa associated microbiota and its enhanced adhesion to epithelium in colorectal carcinogenesis insights from in vivo and clinical studies
url https://doi.org/10.1371/journal.pone.0320383
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