Oral microbiota signatures in obesity with or without acanthosis nigricans in a Chinese cohort

Abstract

Introduction. The oral microbiota is the second most complex microbial community in the human body. It has been suggested that poor oral health may be associated with an increased risk of obesity.Hypothesis/Gap Statement. However, both previous observational and mechanistic studies on oral microbiota do not take into account the obesity-related acanthosis nigricans (AN), which is the most common dermatological manifestation in individuals with obesity.Aim. This study aimed to investigate the altered composition, function and diagnostic value of the oral microbiota in obesity with or without acanthosis nigricans (AN).Methodology. We characterized the oral bacteria signature in a Chinese cohort (ChiCTR2300073353) of 99 patients with obesity and obesity-related AN (Ob_AN) and 50 healthy controls using 16S rRNA gene V3-V4 region sequencing.Results. The microbial richness (abundance-based coverage estimators and observed species indices) was significantly greater in the Ob_AN and obesity groups than in the control group; however, microbial diversity (Shannon index) did not differ significantly. Distinct separation in the microbial community amongst the three groups was observed. Prevotella species, including Prevotella melaninogenica, Prevotella nanceiensis and Prevotella pallens, were associated with composition alterations and predicted functions (significant downregulation of ATP-binding cassette transporters) associated with microbial dysbiosis in the obesity and Ob_AN groups. Moreover, Prevotella and Lautropia genera assessments could indicate obesity and obesity-related AN risk.Conclusions. The notable reduction of plenty of oral microbiota and high levels of Prevotella spp. may play a critical role in obesity with AN. Oral microbiota may serve as biomarkers for diagnosing, preventing and even treating obesity-related AN.

Keywords: Prevotella; acanthosis nigricans; bacteria; obesity; oral microbiota.

Fig. 1.. Oral microbial diversity in patients with obesity or obesity with AN. (a–d) Microbial alpha diversity was estimated based on ACE (a), observed species (b), Faith’s PD (c) and Shannon (d) indices in the healthy control (n=50), obesity (n=49) and obesity with AN (Ob_AN, n=50) subgroups. Different lowercase letters indicate significant differences (P<0.05). (e–g) Beta diversity of Bray–Curtis (e), Jaccard (f) and unweighted UniFrac (g) distances in the three groups based on PCoA. Different lowercase letters in a–d indicated significant differences (P<0.05).

Fig. 2.. Oral microbial composition in patients with obesity or obesity with AN. (a) Top 15 genera in the healthy control, obesity and obesity with AN (Ob_AN) subgroups at the ASV level. (b) The top 16 taxonomic species are shown for the three groups at the ASV level.

Fig. 3.. Microbial biomarker analysis between groups using LEfSe. The numbers correlate with Table S1 and indicate the taxonomic name of the related taxa. A total of 5, 12 and 53 taxa were biomarkers in the obesity, obesity with AN (Ob_AN) and control groups, respectively. LDA score (log 10) cutoff>3.0.

Fig. 4.. Varieties of Prevotella spp. in the oral cavity of patients with obesity or obesity with AN. (a) A total of 43 species were identified. (b) Replot of species P. nigrescens to uncultured Prevotellaceae in panel (a). A Kruskal–Wallis test was used. *P<0.05, **P<0.01 and ***P<0.001 when compared to the control group.

Fig. 5.. Alterations in the predicted metagenome functions in different groups. The top 20 significant KEGG pathways (a) and orthologues (b) are shown. A Kruskal–Wallis test was used. ***P<0.001 amongst three groups.

Fig. 6.. Sankey diagram of predicted pathways and microbial species. A Spearman correlation analysis was performed; rho cutoff >0.7. Left nodes: predicted pathways; middle nodes: microbial species; right nodes: species-related microbial genera. The flows indicated that the pathways were positively linked to microbiota.

Fig. 7.. Evaluation of the distinguishable value of oral microbiota through ROC curve analysis. The top 10 genera that can effectively distinguish obesity (a) or obesity with AN (Ob_AN) samples (b) from healthy control samples are shown.