Correlation Analysis of Gut Microbiota and Serum Metabolome With Porphyromonas gingivalis-Induced Metabolic Disorders

Abstract

Periodontitis has been demonstrated to increase the risk of metabolic syndrome (MetS), but the underlying mechanism remains unclear. Recent studies have indicated periodontopathic bacteria such as Porphyromonas gingivalis could induce gut microbiota (GM) dysbiosis and aggravate metabolic disorders. However, the effects of microbial metabolites have barely been evaluated. Here, we investigated the alteration of serum metabolome with P. gingivalis-induced metabolic disorders, and explored the correlations of GM and serum metabolites. In this study, we orally administered P. gingivalis ATCC33277 to C57BL/6 mice and performed metagenomic sequencing and untargeted metabolomics with fecal samples and serum collection. In vivo experiments showed a higher proportion of fat mass and worse glucose tolerance in P. gingivalis-administered mice, accompanied with an increase of adipose inflammation and gut permeability, which was similar to HFD-induced obese mice. Metagenomic sequencing indicated a compositional and functional alteration of GM. Untargeted metabolomics revealed an alteration of metabolites in P. gingivalis-administered mice, and most of them were engaged in metabolic pathways, such as tryptophan metabolism and choline metabolism. Correlation analysis between GM and serum metabolome indicated strong relativity with P. gingivalis administration. These results demonstrated some specific microbiota-derived metabolites in the pathogenesis of P. gingivalis-induced metabolic disorders, providing promising targets for the development of novel treatment strategies for MetS.

Multi-omics insights reveal the remodeling of gut mycobiome with P. gingivalis

“…Microbial metabolites are key factors in host–microbiota crosstalk. Our previous analysis confirmed 39 metabolism-related metabolites with P. gingivalis administration with untargeted metabolomics profiling ( Dong et al., 2022 ). To further identify correlations between the fungi species and metabolic features that differed between the two groups, we integrated the two datasets using supervised analysis, and a strong correlation was concluded ( r = 0.83) ( Figure 6A ).…”

“…Broad associations between the gut mycobiome and the gut bacteriome and intestinal metabolites have been illustrated in recent studies ( Shah et al., 2021 ; Shuai et al., 2022 ). Our previous research concerning the function of gut bacteria revealed that the “tryptophan metabolism pathway” was significantly altered with P. gingivalis administration and that indole and its derivatives were downregulated ( Dong et al., 2022 ). Here, P. pennisetigena was shown to positively correlate with lipid metabolism-related metabolites, such as LysoPC, and negatively correlate with indole-3-acetamide, 5-hydroxy-tryptophan, and indoleacetaldehyde, which might be a potential reason for its correlation with the metabolic pathway.…”

“…The serum samples were collected for untargeted metabolomics at Majorbio. The detailed information was demonstrated in our previous report (Dong et al, 2022).…”

“…Despite the emerging evidence of the importance of the gut mycobiome and fungi–bacterial interactions in health and disease, little research has focused on the remodeling of gut mycobiome with P. gingivalis . Our previous research demonstrated alterations in the gut bacteriome and serum metabolite profile induced by P. gingivalis administration ( Dong et al., 2022 ). In this study, we aimed to demonstrate the alteration of the gut mycobiome with P. gingivalis administration, investigate the interaction between the gut mycobiome and bacteriome, especially P. gingivalis , and further explore the correlation of the gut mycobiome and serum metabolites preliminarily.…”

Inflammation as a link between periodontal disease and obesity

“…A pretreatment with low P. gingivalis induced tolerance in the innate immune response independently of obesity, 49,50 suggesting that the obesity was associated with a chronic and low‐grade inflammation in line with the epidemiological data presented. Human periodontopathogens (eg, P. gingivalis ) can induce a microbiome shift in mice and predispose the animals to metabolic syndrome and obesity‐associated inflammatory and phenotypic changes 51 . There is evidence that mouse models of obesity and diabetes are characterized by impaired immune responses mediated by T and B lymphocytes.…”