Relationship Between the Oral Microbiome and Treatment Efficacy in Esophageal Squamous Cell Carcinoma.

Microbial imbalances have been well elucidated in esophageal adenocarcinoma (EAC), but few studies address the oral microbiota in esophageal squamous cell carcinoma (ESCC). In view of the fact, we aimed to explore the associations of oral microbiota with these patients suffering from ESCC. In our study, a total of 109 individuals were enrolled (control = 53, ESCC = 56). We profiled the microbiota in oral swabs from individuals with control (ConT) and ESCC (ESCCT). 16S rRNA gene sequencing was applied to analyze the microbiome. The α and β diversity differences were tested by Tukey Test and Partial Least Squares Discriminant Analysis (PLS-DA) respectively. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between the two groups. Our results showed that the microbial richness and diversity was a slightly higher in ESCCT groups than that in ConT groups. Bacteroidota, Firmicutes, Proteobacteria, Fusobacteria, Actinobacteria and Patescibacteria were the six dominant bacteria of oral flora in the two groups. When compared with control group, increased Fusobacterioa at phylum level, Neisseriaceae at family level and Leptotrichia at genus level were detected. LEfSe analysis indicated a greater abundance of Leptotrichiaceae, Leptotrichia, Fusobacteriales, Fusobacteria and Fusobacteriota in ESCC groups. Our study suggests a potential association between oral microbiome dysbiosis and ESCC and provides insights on a potential screening marker for esophageal cancer.

Gut microbiota dysbiosis is closely associated with intestinal carcinogenesis, but the oral microbiota of patients with esophageal squamous cell carcinoma who live in high-risk regions in China has not been fully characterized. In the current study, oral microbial diversity was investigated in 33 patients with esophageal squamous cell carcinoma and 35 healthy controls in Chongqing, China, by sequencing 16S rRNA of V3-V4 gene regions. There were statistically significant differences in oral microbiota between esophageal squamous cell carcinoma patients and controls as determined via unweighted pair-group analysis with arithmetic means. At the phylum level, in esophageal squamous cell carcinoma patients, there were comparatively greater amounts of Firmicutes (34.0% vs. 31.1%) and Bacteroidetes (25.3% vs. 24.9%) and lower amounts of Proteobacteria (17.0% vs. 20.1%). At the genus level, esophageal squamous cell carcinoma patients exhibited comparatively greater amounts of Streptococcus (17.3% vs. 14.5%) and Prevotella_7 (8.6% vs. 8.5%) and lower amounts of Neisseria (8.1% vs. 10.7%). Using a linear discriminant analysis effect size method, Planctomycetes and Verrucomicrobia were identified in the esophageal squamous cell carcinoma group. 10 genera were higher abundances identified in the healthy control group, and different 10 genera were identified in the esophageal squamous cell carcinoma group. In the present study, there were significant differences in oral microbial compositions of esophageal squamous cell carcinoma patients and healthy controls. Further longitudinal and mechanistic studies are needed to further characterize relationships between oral microbiota and esophageal squamous cell carcinoma.

Important evidence indicates that the microbiota plays a key role in esophageal squamous cell carcinoma (ESCC). Here, paired saliva and brush specimens were obtained from 276 participants undergoing upper gastrointestinal endoscopic examination before or during screening for upper gastrointestinal (UGI) cancer. The esophageal microbiota was investigated by 16S rRNA gene profiling and next-generation sequencing. We observed that as the disease progressed, the α diversity in the saliva and cell brush samples decreased. Linear discriminant analysis effect size (LEfSe) results showed that in both the saliva and cell brush specimens, Granulicatella, Rothia, Streptococcus, Gemella, Leptotrichia and Schaalia were common biomarkers in patients with low-grade dysplasia, Lactobacillus was a common biomarker in patients with high-grade dysplasia, and Bosea, Solobacterium, Gemella, and Peptostreptococcus were common biomarkers in patients with esophageal cancer. The top 3 genera in the saliva and cell brush specimens had areas under the curve (AUCs) of 87.16 and 89.13%, respectively, to distinguish ESCC patients from normal people. The PICRUSt2 results identified in brush samples that patients with ESCC had decreased nitrate reductase functions. Our results suggest that future studies can focus on the function of the characteristic bacteria in ESCC.

Animal farming and the oral microbiome in the Agricultural Health Study.

Esophageal squamous cell carcinoma (ESCC) is one of the most predominant subtypes of esophageal cancer. The characteristics of the gut microbiome and its metabolites from patients with ESCC have not been adequately studied and discussed. In this study, 40 fecal samples (20 from ESCC patients and 20 from healthy controls) were analyzed by 16S rRNA gene sequencing and untargeted metabolomics. The data sets were analyzed individually and synthesized using various bioinformatics methods. Alpha and beta diversity indicated significant differences in microbial diversity and abundance between ESCC and healthy control feces. At the genus level, the abundance of Phascolarctobacterium, Sutterella, and Streptococcus was significantly increased in ESCC. At the genus level, linear discriminant analysis effect size identified two biomarkers: Bacteroides_stercoris and Prevotella_copri. Untargeted metabolomics analysis revealed 307 differential metabolites between ESCC and healthy control feces, with indoles and derivatives, tropane alkaloids, lipids, and lipid-like molecules in higher relative abundance in ESCC feces than in healthy control feces. Kyoto Encyclopedia of Genes and Genomes enrichment analysis revealed that unsaturated fatty acids (FAs), ascorbate and aldarate metabolism, and hypoxia-inducible factor 1 signaling pathway were significantly associated with differential metabolite. Phenylethanolamine and despropionyl p-fluoro fentanyl could be used as reliable biomarkers to differentiate ESCC from healthy control. The correlation analysis showed that Prevotella may be involved in the synthesis of fatty acyl, carboxylic acids and derivatives, benzenes and substituted derivatives, organic oxygenates, and indoles and derivatives as metabolites. Fusicatenibacter and Lachnospira may be involved in the degradation of indoles and derivatives. Alistipes, Agathobacter, and Parabacteroides may be involved in the synthesis of indoles and derivatives with strong contributions. There is an intricate relationship between the gut microbiome and the levels of several metabolites (e.g., fatty acyls, carboxylic acids and derivatives, indoles, and derivatives). Microbial-associated metabolites can be used as diagnostic biomarkers in therapeutic exploration. Further analysis revealed that Prevotella, Alistipes, Agathobacter, and Parabacteroides might promote ESCC by regulating the synthesis of indoles and their derivatives. The results of this study provide favorable evidence for the early diagnosis of ESCC and subsequent individualized treatment and targeted interventions.IMPORTANCEWe describe for the first time the differences in fecal microbiome composition and metabolites between patients with esophageal squamous cell carcinoma (ESCC) and healthy controls by 16S rRNA gene sequencing and untargeted metabolomics. The results of this study provide a favorable basis for the early diagnosis of ESCC and subsequent targeted interventional therapy.

ObjectiveTo prospectively investigate whether diversity in oral microbiota is associated with risk of lung cancer among never-smokers.Design and settingA nested case–control study within two prospective cohort studies, the Shanghai Women’s...

Microbial and epidemiological factors in early detection of esophageal squamous cell carcinoma and precancerous lesions.

PurposeThe diversity and composition of the oral and gut microbiota of depressed rats were analyzed to explore the microbiological etiology of major depressive disorder (MDD).MethodsThe depressed rat model was established by inducing chronic unpredictable mild stress (CUMS). After the establishment of the model, body weight measurements and behavioral tests were conducted. The diversity and composition of oral and gut microbiota were analyzed using 16SrRNA sequencing.ResultsThere were significant differences in the alpha and beta diversity of the oral microbiota of rats in the CUMS and control groups. The top three most abundant genera in the oral microbiota were Rothia, Psychrobacter, and Streptococcus. Linear discriminant analysis effect size (LEfSe) analysis showed that the abundance of Rothia decreased and that of Psychrotrophs increased in the CUMS group, and the differences were statistically significant. The top three most abundant genera in the gut microbiota were Lactobacillus, Ruminococcus and Oscillospira. LEfSe analysis showed that the abundance of Ruminococcus decreased in the CUMS group, and the difference was statistically significant. Spearman correlation analysis was performed to analyze the differential microbiota and depression-like behavior, which showed that differential microbiota significantly correlated with body weight, total distance traveled, average speed, and number of rearing. Spearman correlation analysis of oral and gut differential microbiota demonstrated a strong positive correlation between Facklamia in the oral cavity and Enterococcus, Streptococcus in the intestine (r=0.64–0.73, P<0.01); along with a strong negative correlation between Desulfovibrio in the oral cavity and Enterococcus, Turicibacter in the intestine(r=−0.51-−0.72, P<0.05).ConclusionSignificant differences were observed in the diversity and composition of oral and gut microbiota between the CUMS depression model and control groups. Modulating the oral and gut microbiota may have positive effects on MDD.

The endogenous microbiome of healthy individuals in oral cavities is diverse, representing over 700 bacterial species. Imbalance in oral and gut microbiome composition and associated gene expression has been linked to different forms of hematological (blood) cancers. Our objective is to compare oral microbiome profiles of patients with blood cancers (BC group: N = 39 patients, n = 124 oral samples) to those of healthy control subjects (HC group: N = 27 subjects, n = 100 oral samples). Saliva samples and swabs of buccal mucosa, supragingival plaque, and tongue were collected from blood cancer patients and healthy controls. Next-generation sequencing (16S-rRNA gene V3–V4 region) was used to determine the relative abundance of bacterial taxa present at the genus and species levels. Differences in oral microbiome beta-diversity were determined using multivariate permutational analysis of variance (PERMANOVA). Linear discriminant analysis (LDA) effect size (LEfSe) analysis was performed to identify differentiating bacterial taxa in pairwise comparisons. The PATRICv3.6.7 online tool was used to determine the predominance of potential pathogenicity in the BC group. The oral microbiome beta-diversities of the BC and HC groups differed and corresponded to a reduced alpha-diversity in the BC group. LEfSe analysis showed significant LDA scores for Actinomyces and Rothia spp., differentiating the BC group from the HC group. In silico analysis using PATRICv3.6.7 demonstrated that the groups of bacteria possessing traits of “antibiotic resistance”, “oral pathogen”, and “virulence” was enriched in the BC group. Although 56% of the BC patients received antibiotics within two weeks of the oral bacterial sampling, Actinomyces genus remained the top differentiating feature in the BC group regardless of the administration of antibiotics, while Rothia dentocariosa was detected as the top differentiating feature in the BC patients who did not receive antibiotics, but not in those who received antibiotics. Further investigation is needed to better understand the interactions of certain oral species with the host immune system to better characterize clinically relevant associations with hematological cancers.

BackgroundOral microbiome dysbacteriosis has been reported to be associated with the pathogenesis of advanced esophageal cancer. However, few studies investigated the potential role of oral and gastric microbiota in early-stage intramucosal esophageal squamous carcinoma (EIESC).MethodA total of 104 samples were collected from 31 patients with EIESC and 21 healthy controls. The compositions of oral and gastric microbiota were analyzed using 16 S rRNA V3-V4 amplicon sequencing. Linear discriminant analysis effect size (LEfSe) analysis was performed to assess taxonomic differences between groups. The correlation between oral microbiota and clinicopathological factors was evaluated using Spearman correlation analysis. Additionally, co-occurrence networks were established and random forest models were utilized to identify significant microbial biomarkers for distinguishing between the EIESC and control groups.ResultsA total of 292 oral genera and 223 species were identified in both EIESC and healthy controls. Six oral genera were remarkably enriched in EIESC groups, including the genera Porphyromonas, Shigella, Subdoligranulum, Leptotrichia, Paludibacter, and Odoribacter. LEfSe analysis identified genera Porphyromonas and Leptotrichia with LDA scores > 3. In the random forest model, Porphyromonas endodontalis ranked the top microbial biomarker to differentiate EIESC from controls. The elimination rate of Porphyromonas endodontalis from the oral cavity to the stomach was also dramatically decreased in the EIESC group than controls. In the microbial co-occurrence network, Porphyromonas endodontalis was positively correlated with Prevotella tannerae and Prevotella intermedia and was negatively correlated with Veillonella dispar.ConclusionOur study potentially indicates that the dysbacteriosis of both the oral and gastric microbiome was associated with EIESC. Larger scale studies and experimental animal models are urgently needed to confirm the possible role of microbial dysbacteriosis in the pathogenesis of EIESC. (Chinese Clinical Trial Registry Center, ChiCTR2200063464, Registered 07 September 2022, https://www.chictr.org.cn/showproj.html?proj=178563)

BackgroundThe sociobiome refers to the social and socioeconomic conditions that shape human microbial communities, linking structural inequities to biological changes in the microbiome. The aim of this study was to examine how individual and neighbourhood socioeconomic status (SES) are associated with the oral microbiota and dental caries in Indigenous Australian adults.MethodsThis cross-sectional study involved 100 Indigenous Australian participants aged ≥ 18 years and was embedded within a decolonising, community−based participatory research framework. Demographic, socioeconomic, and oral health behaviour data were collected, followed by a dental examination and collection of saliva and plaque samples. The samples were analysed using 16S rRNA amplicon sequencing, and alpha and beta diversity, redundancy analysis, and differential abundance analysis were conducted. Mediation models were used to examine associations between income (Healthcare card ownership), education (≤ secondary), the oral microbiome, and dental caries.ResultsThe microbiome analyses showed saliva had higher alpha diversity (p < 0.01), and beta diversity was significantly different between saliva and plaque (adonis p < 0.001). In saliva, alpha diversity was lower with advancing age, secondary education, income, Healthcare card ownership, and dental caries presence. Beta diversity in saliva microbiome composition showed a stronger association with SES than plaque, with income source (R²=3.8%, p < 0.01), education (R²=2.0%, p < 0.01), and dental caries (R²=2.2%, p < 0.01). Differential abundance analysis showed that the Rikenellaceae RC9 gut group, F0058, Fillifactor, and Treponema were elevated in the low-SES and caries groups. Mediation analysis showed that 75% of the impact of low income on caries was mediated via microbiome shifts, compared with 21% for education, highlighting the strong role of oral microbiome alterations in SES-driven caries risk.ConclusionSocioeconomic disadvantage is associated with variations in the oral microbiome, and these microbial patterns may explain the link between lower income and dental health caries. Saliva may serve as a sensitive biomarker of socioeconomic gradients in oral health. These findings support integrated approaches that address structural determinants of disadvantage alongside microbiome-informed preventive strategies when tackling oral health inequities in Indigenous populations.

IntroductionThe aim of the present study was to characterize the profile and diversity of the oral microbiome of a periodontally non-severe group with ≥20 teeth in comparison with a severe periodontitis group of elderly Japanese people.MethodsA total of 50 patients who had ≥20 teeth and aged ≥60 years were recruited, and 34 participants (13 non-severe participants) were analyzed. After oral rinse (saliva after rinsing) sample collection, the V3–V4 regions of the 16S rRNA gene were sequenced to investigate microbiome composition, alpha diversity (Shannon index, Simpson index, richness, and evenness), and beta diversity using principal coordinate analysis (PCoA) based on weighted and unweighted UniFrac distances. A linear discriminant analysis effect size was calculated to identify bacterial species in the periodontally non-severe group.ResultsThe periodontally non-severe group showed lower alpha diversity than that of the severe periodontitis group (p <0.05); however, the beta diversities were not significantly different. A higher relative abundance of four bacterial species (Prevotella nanceiensis, Gemella sanguinis, Fusobacterium periodonticum, and Haemophilus parainfluenzae) was observed in the non-severe group than that in the severe periodontitis group.ConclusionThe oral microbiome in elderly Japanese people with ≥20 teeth and a non-severe periodontal condition was characterized by low alpha diversity and the presence of four bacterial species.

&lt;div&gt;Abstract&lt;p&gt;Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20–75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;difference&lt;/sub&gt; &lt; 0.01) and distinct biological communities (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;difference&lt;/sub&gt; = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded &gt;8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14–20.94) and 10.72 (3.30–34.84), respectively] with similar findings for the inverse Simpson index. &lt;i&gt;Streptococcus&lt;/i&gt; was enriched among women who did not develop cancer, while &lt;i&gt;Fusobacterium, Prevotella, Mogibacterium, Campylobacter, Lachnoanaerobaculum, Dialister&lt;/i&gt;, and &lt;i&gt;Atopobium&lt;/i&gt; were higher among women who developed cancer (LDA score ≥ 3; q-value &lt; 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker.&lt;/p&gt;Prevention Relevance:&lt;p&gt;Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.&lt;/p&gt;&lt;/div&gt;

&lt;div&gt;Abstract&lt;p&gt;Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20–75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted &lt;i&gt;P&lt;/i&gt;&lt;sub&gt;difference&lt;/sub&gt; &lt; 0.01) and distinct biological communities (&lt;i&gt;P&lt;/i&gt;&lt;sub&gt;difference&lt;/sub&gt; = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded &gt;8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14–20.94) and 10.72 (3.30–34.84), respectively] with similar findings for the inverse Simpson index. &lt;i&gt;Streptococcus&lt;/i&gt; was enriched among women who did not develop cancer, while &lt;i&gt;Fusobacterium, Prevotella, Mogibacterium, Campylobacter, Lachnoanaerobaculum, Dialister&lt;/i&gt;, and &lt;i&gt;Atopobium&lt;/i&gt; were higher among women who developed cancer (LDA score ≥ 3; q-value &lt; 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker.&lt;/p&gt;Prevention Relevance:&lt;p&gt;Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.&lt;/p&gt;&lt;/div&gt;

Given the increasing evidence that the oral microbiome is involved in obesity, diabetes, and cancer risk, we investigated baseline oral microbiota profiles in relation to all-cancer incidence among nonsmoking women enrolled in a Texas cohort of first- and second-generation immigrants of Mexican origin. We characterized the 16Sv4 rDNA microbiome in oral mouthwash samples collected at baseline from a representative subset of 305 nonsmoking women, ages 20-75 years. We evaluated within- (alpha) and between-sample (beta) diversity by incident cancer status and applied linear discriminant analysis (LDA) effect size analysis to assess differentially abundant taxa. Diversity and candidate taxa in relation to all-cancer incidence were evaluated in multivariable-adjusted Cox regression models. Over 8.8 median years of follow-up, 31 incident cancer cases were identified and verified. Advanced age, greater acculturation, and cardiometabolic risk factors were associated with all-cancer incidence. Higher alpha diversity (age-adjusted P difference < 0.01) and distinct biological communities (P difference = 0.002) were observed by incident cancer status. Each unit increase in the Shannon diversity index yielded >8-fold increase in all-cancer and obesity-related cancer risk [multivariable-adjusted HR (95% confidence interval), 8.11 (3.14-20.94) and 10.72 (3.30-34.84), respectively] with similar findings for the inverse Simpson index. Streptococcus was enriched among women who did not develop cancer, while Fusobacterium, Prevotella, Mogibacterium, Campylobacter, Lachnoanaerobaculum, Dialister, and Atopobium were higher among women who developed cancer (LDA score ≥ 3; q-value < 0.01). This initial study of oral microbiota and overall cancer risk in nonsmoking Mexican American women suggests the readily accessible oral microbiota as a promising biomarker. PREVENTION RELEVANCE: Mexican American women suffer a disproportionate burden of chronic health conditions that increase cancer risk. Few investigations of the microbiome, a key determinant of host health, have been conducted among this group. Oral microbiota profiles may provide early and accessible cancer biomarker data on invasive bacteria or community disruptions.