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Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracell...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961321/ https://www.ncbi.nlm.nih.gov/pubmed/35360107 http://dx.doi.org/10.3389/fcimb.2022.776996 |
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author | Wu, Leng Shi, Rui Bai, Huimin Wang, Xingtong Wei, Jian Liu, Chengcheng Wu, Yafei |
author_facet | Wu, Leng Shi, Rui Bai, Huimin Wang, Xingtong Wei, Jian Liu, Chengcheng Wu, Yafei |
author_sort | Wu, Leng |
collection | PubMed |
description | Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular P. gingivalis and infected host cells via dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of P. gingivalis livk and livh genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by P. gingivalis, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury via livh/livk. To verify this hypothesis, we constructed P. gingivalis livh/livk-deficient strains (Δlivk, Δlivh) and established a high-fat diet (HFD)-fed murine model infected with P. gingivalis. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and in vivo colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that P. gingivalis infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, livh deletion had no effect on bacterial growth, EPS production, invasion efficiency, and in vivo colonization, whereas the Δlivk strain showed a slight decrease in invasion efficiency and in vivo colonization. More importantly, however, both the Δlivk and Δlivh strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that P. gingivalis possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system. |
format | Online Article Text |
id | pubmed-8961321 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89613212022-03-30 Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk Wu, Leng Shi, Rui Bai, Huimin Wang, Xingtong Wei, Jian Liu, Chengcheng Wu, Yafei Front Cell Infect Microbiol Cellular and Infection Microbiology Porphyromonas gingivalis, a keystone periodontal pathogen, has emerged as a risk factor for systemic chronic diseases, including non-alcoholic fatty liver disease (NAFLD). To clarify the mechanism by which this pathogen induces such diseases, we simultaneously analyzed the transcriptome of intracellular P. gingivalis and infected host cells via dual RNA sequencing. Pathway analysis was also performed to determine the differentially expressed genes in the infected cells. Further, the infection-induced notable expression of P. gingivalis livk and livh genes, which participate in branched-chain amino acid (BCAA) transfer, was also analyzed. Furthermore, given that the results of recent studies have associated NAFLD progression with elevated serum BCAA levels, which reportedly, are upregulated by P. gingivalis, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury via livh/livk. To verify this hypothesis, we constructed P. gingivalis livh/livk-deficient strains (Δlivk, Δlivh) and established a high-fat diet (HFD)-fed murine model infected with P. gingivalis. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and in vivo colonization of the mutant strains were compared with those of the parental strain. The serum BCAA and fasting glucose levels of the mice infected with either the wild-type or mutant strains, as well as their liver function were also further investigated. It was observed that P. gingivalis infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, livh deletion had no effect on bacterial growth, EPS production, invasion efficiency, and in vivo colonization, whereas the Δlivk strain showed a slight decrease in invasion efficiency and in vivo colonization. More importantly, however, both the Δlivk and Δlivh strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that P. gingivalis possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8961321/ /pubmed/35360107 http://dx.doi.org/10.3389/fcimb.2022.776996 Text en Copyright © 2022 Wu, Shi, Bai, Wang, Wei, Liu and Wu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Cellular and Infection Microbiology Wu, Leng Shi, Rui Bai, Huimin Wang, Xingtong Wei, Jian Liu, Chengcheng Wu, Yafei Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk |
title | Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
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title_full | Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
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title_fullStr | Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
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title_full_unstemmed | Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
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title_short | Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk
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title_sort | porphyromonas gingivalis induces increases in branched-chain amino acid levels and exacerbates liver injury through livh/livk |
topic | Cellular and Infection Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8961321/ https://www.ncbi.nlm.nih.gov/pubmed/35360107 http://dx.doi.org/10.3389/fcimb.2022.776996 |
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