Dataset Information

From Mouth to Muscle: Exploring the Potential Relationship between the Oral Microbiome and Cancer-Related Cachexia.

ABSTRACT: Cancer cachexia is a multifactorial wasting syndrome associated with skeletal muscle and adipose tissue loss, as well as decreased appetite. It affects approximately half of all cancer patients and leads to a decrease in treatment efficacy, quality of life, and survival. The human microbiota has been implicated in the onset and propagation of cancer cachexia. Dysbiosis, or the imbalance of the microbial communities, may lead to chronic systemic inflammation and contribute to the clinical phenotype of cachexia. Though the relationship between the gut microbiome, inflammation, and cachexia has been previously studied, the oral microbiome remains largely unexplored. As the initial point of digestion, the oral microbiome plays an important role in regulating systemic health. Oral dysbiosis leads to the upregulation of pro-inflammatory cytokines and an imbalance in natural flora, which in turn may contribute to muscle wasting associated with cachexia. Reinstating this equilibrium with the use of prebiotics and probiotics has the potential to improve the quality of life for patients suffering from cancer-related cachexia.

SUBMITTER: Raman SR

PROVIDER: S-EPMC9693534 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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From Mouth to Muscle: Exploring the Potential Relationship between the Oral Microbiome and Cancer-Related Cachexia.

Raman Shreya R SR Liu Christopher C Herremans Kelly M KM Riner Andrea N AN Vudatha Vignesh V Freudenberger Devon C DC McKinley Kelley L KL Triplett Eric W EW Trevino Jose G JG

Microorganisms 20221118 11

Cancer cachexia is a multifactorial wasting syndrome associated with skeletal muscle and adipose tissue loss, as well as decreased appetite. It affects approximately half of all cancer patients and leads to a decrease in treatment efficacy, quality of life, and survival. The human microbiota has been implicated in the onset and propagation of cancer cachexia. Dysbiosis, or the imbalance of the microbial communities, may lead to chronic systemic inflammation and contribute to the clinical phenoty ...[more]

PMID: 36422360

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Project description:BackgroundAlthough the association between mouth ulcers and psychiatric traits has been reported by observational studies, their causal relationship remains unclear. Mendelian randomization (MR), powered by large-scale genome-wide association studies (GWAS), provides an opportunity to clarify the causality between mouth ulcers and psychiatric traits.MethodsWe collected summary statistics of mouth ulcers (sample size n = 461,106) and 10 psychiatric traits from the largest publicly available GWAS on Europeans, including anxiety disorder (n = 83,566), attention deficit/hyperactivity disorder (n = 53,293), autism spectrum disorder (n = 46,350), bipolar disorder (n = 51,710), insomnia (n = 1,331,010), major depressive disorder (n = 480,359), mood instability (n = 363,705), neuroticism (n = 168,105), schizophrenia (n = 105,318), and subjective wellbeing (n = 388,538). We applied three two-sample bi-directional MR analysis methods, namely the Inverse Variance Weighted (IVW) method, the MR pleiotropy residual sum and outlier (MR-PRESSO) method, and the weighted median method, to assess the causal relationship between each psychiatric trait and mouth ulcers.ResultsWe found significant effects of autism spectrum disorder, insomnia, major depressive disorder, and subjective wellbeing on mouth ulcers, with the corresponding odds ratio (OR) from the IVW method being 1.160 [95% confidence interval (CI): 1.066-1.261, P = 5.39 × 10-4], 1.092 (1.062-1.122, P = 3.37 × 10-10), 1.234 (1.134-1.342, P = 1.03 × 10-6), and 0.703 (0.571-0.865, P = 8.97 × 10-4), respectively. We also observed suggestive evidence for mood instability to cause mouth ulcers [IVW, OR = 1.662 (1.059-2.609), P = 0.027]. These results were robust to weak instrument bias and heterogeneity. We found no evidence on causal effects between other psychiatric traits and mouth ulcers, in either direction.ConclusionOur findings suggest a protective effect of subjective wellbeing and risk effects of autism spectrum disorder, insomnia, major depressive disorder, and mood instability on mouth ulcers. These results clarify the causal relationship between psychiatric traits and the development of mouth ulcers.

Project description:BACKGROUND:Cachexia is responsible for the low quality of life in pancreatic adenocarcinoma (PDAC). The rapid disease progression and patient deterioration seems related to perineural invasion, but the relationship between cachexia and perineural invasion for the evolution of the disease has been rarely studied. As perineural invasion is difficult to be highlighted, a biomarker such as the neurotrophic factor Midkine (MK) which promotes the neuronal differentiation and the cell migration could be helpful. Also, Activin (ACV) has been described as cachexia related to PDAC. However, their role for assessing and predicting the disease course in daily practice is not known. AIM:To assess the relationship between perineural invasion and cachexia and their biomarkers, MK and ACV, respectively, and their prognostic value. METHODS:This study included prospectively enrolled patients with proven adenocarcinoma and a matched group of controls without any malignancies. Patients with other causes of malnutrition were excluded. The plasma levels of ACV and MK were analyzed using western blotting and were correlated with the clinicopathological features and survival data. These results were validated by immunohistochemical analyses of the pancreatic tumor tissue of the patients included in the study and a supplementary group of surgically resected specimens from patients with a benign disease. RESULTS:The study comprised 114 patients with PDAC, 125 controls and a supplementary group of 14 benign pancreatic tissue samples. ACV and MK were both overexpressed more frequently in the plasma of patients with PDAC than in the controls (63% vs 32% for ACV, P < 0.001; 47% vs 16% for MK, P < 0.001), with similar levels in pancreatic tissue the MK protein expression was closely related to the advanced clinical stage (P = 0.006), the presence of metastasis (P = 0.04), perineural invasion (P = 0.03) and diabetes (P = 0.002), but with no influence on survival. No correlation between clinicopathological factors and ACV expression was noted. Cachexia, present in 19% of patients, was unrelated to ACV or MK level. Higher ACV expression was associated with a shorter survival (P = 0.008). CONCLUSION:The MK was a biomarker of perineural invasion, associated with tumor stage and diabetes, but without prognostic value as ACV. Cachexia was unrelated to perineural invasion, ACV level or survival.

Project description:ImportanceThe oral microbiome is increasingly recognized to play key roles in human health and disease; yet, population-representative characterizations are lacking.ObjectiveCharacterize the composition, diversity, and correlates of the oral microbiome among US adults.DesignCross-sectional population-representative survey.SettingThe National Health and Nutrition Examination Survey (NHANES, 2009-2012), a stratified multistage probability sample of the US population.ParticipantsNHANES participants aged 18-69 years (n=8,237, representing 202,314,000 individuals).ExposuresDemographic, socioeconomic, behavioral, anthropometric, metabolic, and clinical characteristics.Main outcomesOral microbiome, characterized through 16S rRNA sequencing. Microbiome metrics were alpha diversity (number of observed Amplicon Sequence Variants [ASV], Faith's Phylogenetic diversity, Shannon-Weiner Index, and Simpson Index); beta diversity (unweighted UniFrac, weighted UniFrac, and Bray-Curtis dissimilarity); and prevalence and relative abundance at taxonomic levels (phylum through genus). Analyses accounted for the NHANES complex sample design.ResultsAmong US adults aged 18-69 years, the oral microbiome encompassed 37 bacterial phyla, 99 classes, 212 orders, 446 families, and 1,219 genera. Five phyla-Firmicutes, Actinobacteria, Bacteroidetes, Proteobacteria, and Fusobacteria and six genera-Veillonella, Streptococcus, Prevotella7, Rothia, Actinomyces, and Gemella, were present in nearly all US adults (weighted-prevalence >99%). These genera also were the most abundant, accounting for 65.7% of abundance. Observed ASVs showed a quadratic pattern with age (peak at 30 years), was similar by sex, significantly lower among non-Hispanic White individuals, and increased with higher body mass index (BMI) categories, alcohol use, and periodontal disease severity. All covariates together accounted for a modest proportion of oral microbiome variability, as measured by beta diversity (unweighted UniFrac=8.7%, weighted UniFrac=7.2%, and Bray-Curtis=6.3%). By contrast, relative abundance of a few genera explained a high percentage of variability in beta diversity (weighted UniFrac: Aggregatibacter=22.4%, Lactococcus=21.6%, Haemophilus=18.4%). Prevalence and relative abundance of numerous genera were significantly associated (Bonferroni-corrected Wald-p<0.0002) with age, race and ethnicity, smoking, BMI categories, alcohol use, and periodontal disease severity.ConclusionsWe provide a contemporary reference standard for the oral microbiome of the US adult population. Our results indicate that a few genera were universally present in US adults and a different set of genera explained a high percentage of oral microbiome diversity across the population.

Dataset Information

From Mouth to Muscle: Exploring the Potential Relationship between the Oral Microbiome and Cancer-Related Cachexia.

Publications

From Mouth to Muscle: Exploring the Potential Relationship between the Oral Microbiome and Cancer-Related Cachexia.

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