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<p>Obesity and smoking are major global health threats with synergistic impacts on metabolic disease. The combined effects of these factors on the oral-gut (Orointestinal) microbiome axis, a crucial interface for systemic immunity and metabolism, remain poorly characterized. In this cross-sectional study, 108 age- and sex-matched participants were stratified into four groups (<i>n</i> = 27/group): Non-Obese Non-Smokers (Control), Obese Non-Smokers, Non-Obese Smokers, and Obese-Smokers. Orointestinal microbiomes were profiled via 16&#xa0;S rRNA sequencing of stool and oral rinse samples, followed by comprehensive bioinformatics analysis. Compartment-specific patterns existed in relation to smoking and obesity. The oral microbiome of Obese-Smokers exhibited a significant, dose-dependent reduction in diversity (34% loss at &gt; 20 cigarettes/day; <i>padj =</i> 0.008), synergistic depletion of oral commensals such as <i>Elizabethkingia</i> (log<sub>2</sub>FC = − 6.33, <i>padj</i> = 0.0032) and enrichment of pathobionts such as <i>Escherichia_Shigella</i> (log<sub>2</sub>FC = 3.2, <i>padj =</i> 0.00068). In contrast, the gut microbiome maintained stable bacterial diversity across groups, despite profound compositional shifts (PERMANOVA, <i>padj</i> = 0.003), with smokers showing a significantly elevated Firmicutes/Bacteroidetes ratio (1.78 vs. 0.91 in controls; <i>padj</i> = 0.006). Critically, Obese-Smokers revealed a significant bidirectional pattern of the Orointestinal axis, specifically in the oral cavity, as evidenced by the significant Orointestinal co-occurrence of the oral pathobionts <i>Neisseria</i> and <i>Leptotrichia</i> (<i>r =</i> 0.67, <i>p =</i> 0.0001), which potentially highlights microbial covariation across habitats. A random forest model identified the oral taxon <i>F0058</i> (Saccharimonadaceae) as a potential biomarker for Obese-Smoker status (AUC = 0.975, <i>padj</i> = 0.017). Obesity and smoking are associated with synergistic orointestinal dysbiosis, pathobiont expansion, commensal loss, and potential microbial covariation across habitats. The vulnerable oral microbiome, specifically the <i>F0058</i> biomarker, offers a promising target for noninvasive risk stratification and intervention.</p>

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Oral-gut microbiome dysbiosis in obese smokers reveals compartment-specific shifts

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年4月13日

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  • Mohammed Ramadan,
  • Esraa K. Hassan,
  • Salah Abdalla,
  • Ali A. Abdelrhman Ahmed,
  • Marwa Azab,
  • Kareem A. Ibrahim,
  • Ibrahim A. Amin,
  • Mohamed Ebid Ali,
  • Ahmed Eid Alharbi,
  • Mohammed Salah

摘要

Obesity and smoking are major global health threats with synergistic impacts on metabolic disease. The combined effects of these factors on the oral-gut (Orointestinal) microbiome axis, a crucial interface for systemic immunity and metabolism, remain poorly characterized. In this cross-sectional study, 108 age- and sex-matched participants were stratified into four groups (n = 27/group): Non-Obese Non-Smokers (Control), Obese Non-Smokers, Non-Obese Smokers, and Obese-Smokers. Orointestinal microbiomes were profiled via 16 S rRNA sequencing of stool and oral rinse samples, followed by comprehensive bioinformatics analysis. Compartment-specific patterns existed in relation to smoking and obesity. The oral microbiome of Obese-Smokers exhibited a significant, dose-dependent reduction in diversity (34% loss at > 20 cigarettes/day; padj = 0.008), synergistic depletion of oral commensals such as Elizabethkingia (log2FC = − 6.33, padj = 0.0032) and enrichment of pathobionts such as Escherichia_Shigella (log2FC = 3.2, padj = 0.00068). In contrast, the gut microbiome maintained stable bacterial diversity across groups, despite profound compositional shifts (PERMANOVA, padj = 0.003), with smokers showing a significantly elevated Firmicutes/Bacteroidetes ratio (1.78 vs. 0.91 in controls; padj = 0.006). Critically, Obese-Smokers revealed a significant bidirectional pattern of the Orointestinal axis, specifically in the oral cavity, as evidenced by the significant Orointestinal co-occurrence of the oral pathobionts Neisseria and Leptotrichia (r = 0.67, p = 0.0001), which potentially highlights microbial covariation across habitats. A random forest model identified the oral taxon F0058 (Saccharimonadaceae) as a potential biomarker for Obese-Smoker status (AUC = 0.975, padj = 0.017). Obesity and smoking are associated with synergistic orointestinal dysbiosis, pathobiont expansion, commensal loss, and potential microbial covariation across habitats. The vulnerable oral microbiome, specifically the F0058 biomarker, offers a promising target for noninvasive risk stratification and intervention.