AUTHOR=Wu Leng , Shi Rui , Bai Huimin , Wang Xingtong , Wei Jian , Liu Chengcheng , Wu Yafei 

TITLE=Porphyromonas gingivalis Induces Increases in Branched-Chain Amino Acid Levels and Exacerbates Liver Injury Through livh/livk

JOURNAL=Frontiers in Cellular and Infection Microbiology

VOLUME=12

YEAR=2022

URL=https://www.frontiersin.org/journals/cellular-and-infection-microbiology/articles/10.3389/fcimb.2022.776996

DOI=10.3389/fcimb.2022.776996

ISSN=2235-2988

ABSTRACT=<p><italic>Porphyromonas gingivalis</italic>, 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 <italic>P. gingivalis</italic> and infected host cells <italic>via</italic> 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 <italic>P. gingivalis livk</italic> and <italic>livh</italic> 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 <italic>P. gingivalis</italic>, we hypothesized that this pathogen may induce increases in serum BCAA levels and exacerbate liver injury <italic>via livh/livk</italic>. To verify this hypothesis, we constructed <italic>P. gingivalis livh/livk</italic>-deficient strains (<italic>Δlivk</italic>, <italic>Δlivh</italic>) and established a high-fat diet (HFD)-fed murine model infected with <italic>P. gingivalis</italic>. Thereafter, the kinetic growth and exopolysaccharide (EPS) production rates as well as the invasion efficiency and <italic>in vivo</italic> 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 <italic>P. gingivalis</italic> infection enhanced serum BCAA levels and aggravated liver injury in the HFD-fed mice. Additionally, <italic>livh</italic> deletion had no effect on bacterial growth, EPS production, invasion efficiency, and <italic>in vivo</italic> colonization, whereas the <italic>Δlivk</italic> strain showed a slight decrease in invasion efficiency and <italic>in vivo</italic> colonization. More importantly, however, both the <italic>Δlivk</italic> and <italic>Δliv</italic>h strains showed impaired ability to upregulate serum BCAA levels or exacerbate liver injury in HFD-fed mice. Overall, these results suggested that <italic>P. gingivalis</italic> possibly aggravates NAFLD progression in HFD-fed mice by increasing serum BCAA levels, and this effect showed dependency on the bacterial BCAA transport system.</p>