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Over the past decade, there has been a change in the epidemiology of oral cavity squamous cell cancer (OC‐SCC). Many new cases of OC‐SCC lack the recognized risk factors of smoking, alcohol and human papilloma virus. The aim of this study was to determine if the oral microbiome may be associated with OC‐SCC in nonsmoking HPV negative patients. We compared the oral microbiome of HPV‐negative nonsmoker OC‐SCC(n = 18), premalignant lesions(PML) (n = 8) and normal control patients (n = 12). Their oral microbiome was sampled by oral wash and defined by 16S rRNA gene sequencing. We report that the periodontal pathogens Fusobacterium, Prevotella, Alloprevotella were enriched while commensal Streptococcus depleted in OC‐SCC. Based on the four genera plus a marker genus Veillonella for PML, we classified the oral microbiome into two types. Gene/pathway analysis revealed a progressive increase of genes encoding HSP90 and ligands for TLRs 1, 2 and 4 along the controls→PML → OC‐SCC progression sequence. Our findings suggest an association between periodontal pathogens and OC‐SCC in non smoking HPV negative patients.

Introduction Epidemiological studies that investigate alterations in the gut microbial composition associated with smoking are lacking. This study examined the composition of the gut microbiome in smokers compared with nonsmokers. Aims and Methods Stool samples were collected in a cross-sectional study of 249 participants selected from the Health Effects of Arsenic Longitudinal Study in Bangladesh. Microbial DNA was extracted from the fecal samples and sequenced by 16S rRNA gene sequencing. The associations of smoking status and intensity of smoking with the relative abundance or the absence and presence of individual bacterial taxon from phylum to genus levels were examined. Results The relative abundance of bacterial taxa along the Erysipelotrichi-to-Catenibacterium lineage was significantly higher in current smokers compared to never-smokers. The odds ratio comparing the mean relative abundance in current smokers with that in never-smokers was 1.91 (95% confidence interval = 1.36–2.69) for the genus Catenibacterium and 1.89 (95% confidence interval = 1.39–2.56) for the family Erysipelotrichaceae, the order Erysipelotrichale, and the class Erysipelotrichi (false discovery rate-adjusted p values = .0008–.01). A dose–response association was observed for each of these bacterial taxa. The presence of Alphaproteobacteria was significantly greater comparing current with never-smokers (odds ratio = 4.85, false discovery rate-adjusted p values = .04). Conclusions Our data in a Bangladeshi population are consistent with evidence of an association between smoking status and dosage with change in the gut bacterial composition. Implications This study for the first time examined the relationship between smoking and the gut microbiome composition. The data suggest that smoking status may play an important role in the composition of the gut microbiome, especially among individuals with higher levels of tobacco exposure.

Background: Despite robust cholesterol lowering, cardiovascular disease risk remains increased in patients with diabetes mellitus. Consistent with this, diabetes mellitus impairs atherosclerosis regression after cholesterol lowering in humans and mice. In mice, this is attributed in part to hyperglycemia-induced monocytosis, which increases monocyte entry into plaques despite cholesterol lowering. In addition, diabetes mellitus skews plaque macrophages toward an atherogenic inflammatory M1 phenotype instead of toward the atherosclerosis-resolving M2 state typical with cholesterol lowering. Functional high-density lipoprotein (HDL), typically low in patients with diabetes mellitus, reduces monocyte precursor proliferation in murine bone marrow and has anti-inflammatory effects on human and murine macrophages. Our study aimed to test whether raising functional HDL levels in diabetic mice prevents monocytosis, reduces the quantity and inflammation of plaque macrophages, and enhances atherosclerosis regression after cholesterol lowering. Methods: Aortic arches containing plaques developed in Ldlr −/− mice were transplanted into either wild-type, diabetic wild-type, or diabetic mice transgenic for human apolipoprotein AI, which have elevated functional HDL. Recipient mice all had low levels of low-density lipoprotein cholesterol to promote plaque regression. After 2 weeks, plaques in recipient mouse aortic grafts were examined. Results: Diabetic wild-type mice had impaired atherosclerosis regression, which was normalized by raising HDL levels. This benefit was linked to suppressed hyperglycemia-driven myelopoiesis, monocytosis, and neutrophilia. Increased HDL improved cholesterol efflux from bone marrow progenitors, suppressing their proliferation and monocyte and neutrophil production capacity. In addition to reducing circulating monocytes available for recruitment into plaques, in the diabetic milieu, HDL suppressed the general recruitability of monocytes to inflammatory sites and promoted plaque macrophage polarization to the M2, atherosclerosis-resolving state. There was also a decrease in plaque neutrophil extracellular traps, which are atherogenic and increased by diabetes mellitus. Conclusions: Raising apolipoprotein AI and functional levels of HDL promotes multiple favorable changes in the production of monocytes and neutrophils and in the inflammatory environment of atherosclerotic plaques of diabetic mice after cholesterol lowering and may represent a novel approach to reduce cardiovascular disease risk in people with diabetes mellitus.

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