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International Journal of Molecular... Feb 2023The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and...
The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL ( = 9), PVL ( = 12), OSCC ( = 10), PVL-OSCC ( = 8), and healthy ( = 11) donors were obtained. The sequence of the V3-V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of and lower than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in , , , , , and ; PVL is enriched in , and ; OSCC is enriched in , and ; and PVL-OSCC is enriched in , and . There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Dysbiosis; RNA, Ribosomal, 16S; Leukoplakia, Oral; Microbiota
PubMed: 36834903
DOI: 10.3390/ijms24043466 -
Scientific Reports Jan 2023As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the...
As geographical location can impact the gut microbiome, it is important to study region-specific microbiome signatures of various diseases. Therefore, we profiled the gut microbiome of breast cancer (BC) patients of the Midwestern region of the United States. The bacterial component of the gut microbiome was profiled utilizing 16S ribosomal RNA sequencing. Additionally, a gene pathway analysis was performed to assess the functional capabilities of the bacterial microbiome. Alpha diversity was not significantly different between BC and healthy controls (HC), however beta diversity revealed distinct clustering between the two groups at the species and genera level. Wilcoxon Rank Sum test revealed modulation of several gut bacteria in BC specifically reduced abundance of those linked with beneficial effects such as Faecalibacterium prausnitzii. Machine learning analysis confirmed the significance of several of the modulated bacteria found by the univariate analysis. The functional analysis showed a decreased abundance of SCFA (propionate) production in BC compared to HC. In conclusion, we observed gut dysbiosis in BC with the depletion of SCFA-producing gut bacteria suggesting their role in the pathobiology of breast cancer. Mechanistic understanding of gut bacterial dysbiosis in breast cancer could lead to refined prevention and treatment.
Topics: Humans; United States; Female; Breast Neoplasms; Dysbiosis; Bacteria; Fatty Acids, Volatile; Gastrointestinal Microbiome; Feces; RNA, Ribosomal, 16S
PubMed: 36631533
DOI: 10.1038/s41598-023-27436-3 -
MSphere Feb 2023The tongue dorsum is colonized by a stable microbiota, mostly comprising common commensal taxa. However, the predominance of each taxon varies among individuals. We... (Observational Study)
Observational Study
The tongue dorsum is colonized by a stable microbiota, mostly comprising common commensal taxa. However, the predominance of each taxon varies among individuals. We hypothesized that equilibrium in the tongue microbiota is affected by exposure to butyrate in the oral fluid, which is reported to affect the growth of specific microorganisms. In this study, the bacterial composition of the tongue microbiotas of 69 male adults was determined via 16S rRNA gene sequencing to investigate its relationship to -butyric acid concentration in oral rinse samples. The tongue microbiotas of individuals with a higher -butyric acid level had higher relative abundances of Prevotella histicola, Veillonella atypica, and Streptococcus parasanguinis and lower relative abundances of Neisseria subflava and Porphyromonas pasteri. Subsequently, tongue microbiota samples collected from 12 adults were cultivated for 13 h in basal medium containing mucin and different concentrations of sodium butyrate (0, 0.8, 1.6, and 3.2 mM) to assess its effect on the growth of tongue microbiota organisms. The bacterial composition of the cultivated tongue microbiotas also demonstrated a significant gradual shift with an increase in sodium butyrate levels in beta-diversity analysis. was significantly less predominant in the microbiota after cultivation with an increased addition of sodium butyrate, although no statistical difference was observed in the other aforementioned taxa. These results suggest that butyrate in the oral fluid is partially involved in the dysbiotic shift of the tongue microbiota. Oral microbial populations that are always ingested with saliva have attracted increasing attention because more oral microorganisms than previously known reach distal organs, such as the lungs and intestinal tract, thereby affecting our health. However, although such organisms are predominately derived from the tongue dorsum, the dynamics and determinants of the tongue microbiota composition remain unclear. This study demonstrated that exposure to butyrate could lead to a dysbiotic shift in the tongue microbiota using an observational epidemiological and microbiota cultivation approach. This result adds a new dimension to tongue microbiota ecology.
Topics: Adult; Humans; Male; Butyric Acid; RNA, Ribosomal, 16S; Tongue; Microbiota; Saliva; Bacteria; Dysbiosis
PubMed: 36507724
DOI: 10.1128/msphere.00490-22 -
Research (Washington, D.C.) 2022The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the...
The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced and and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.
PubMed: 36320634
DOI: 10.34133/2022/9781578 -
Metabolomics : Official Journal of the... Oct 2022Phytoestrogens found in soy, fruits, peanuts, and other legumes, have been identified as metabolites capable of providing beneficial effects in multiple pathological...
INTRODUCTION
Phytoestrogens found in soy, fruits, peanuts, and other legumes, have been identified as metabolites capable of providing beneficial effects in multiple pathological conditions due to their ability to mimic endogenous estrogen. Interestingly, the health-promoting effects of some phytoestrogens, such as isoflavones, are dependent on the presence of specific gut bacteria. Specifically, gut bacteria can metabolize isoflavones into equol, which has a higher affinity for endogenous estrogen receptors compared to dietary isoflavones. We have previously shown that patients with multiple sclerosis (MS), a neuroinflammatory disease, lack gut bacteria that are able to metabolize phytoestrogen. Further, we have validated the importance of both isoflavones and phytoestrogen-metabolizing gut bacteria in disease protection utilizing an animal model of MS. Specifically, we have shown that an isoflavone-rich diet can protect from neuroinflammatory diseases, and that protection was dependent on the ability of gut bacteria to metabolize isoflavones into equol. Additionally, mice on a diet with isoflavones showed an anti-inflammatory response compared to the mice on a diet lacking isoflavones. However, it is unknown how isoflavones and/or equol mediates their protective effects, especially their effects on host metabolite levels.
OBJECTIVES
In this study, we utilized untargeted metabolomics to identify metabolites found in plasma that were modulated by the presence of dietary isoflavones.
RESULTS
We found that the consumption of isoflavones increased anti-inflammatory monounsaturated fatty acids and beneficial polyunsaturated fatty acids while reducing pro-inflammatory glycerophospholipids, sphingolipids, phenylalanine metabolism, and arachidonic acid derivatives.
CONCLUSION
Isoflavone consumption alters the systemic metabolic landscape through concurrent increases in monounsaturated fatty acids and beneficial polyunsaturated fatty acids plus reduction in pro-inflammatory metabolites and pathways. This highlights a potential mechanism by which an isoflavone diet may modulate immune-mediated disease.
Topics: Animals; Mice; Isoflavones; Equol; Phytoestrogens; Lipid Metabolism; Receptors, Estrogen; Phenylalanine; Metabolomics; Estrogens; Bacteria; Inflammation; Fatty Acids, Monounsaturated; Sphingolipids; Glycerophospholipids; Arachidonic Acids
PubMed: 36289122
DOI: 10.1007/s11306-022-01944-1 -
Dietary Isoflavones Alter Gut Microbiota and Lipopolysaccharide Biosynthesis to Reduce Inflammation.Gut Microbes 2022The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was...
The etiopathogenesis of multiple sclerosis (MS) is strongly affected by environmental factors such as diet and the gut microbiota. An isoflavone-rich (ISO) diet was previously shown to reduce the severity of MS in the animal model experimental autoimmune encephalomyelitis (EAE). Translation of this concept to clinical trial where dietary isoflavones may be recommended for MS patients will require preliminary evidence that providing the isoflavone-rich diet to people with MS (PwMS) who lack phytoestrogen-metabolizing bacteria has beneficial effects. We have previously shown that the gut microbiota of PwMS resembles the gut microbiota of mice raised under a phytoestrogen-free (phyto-free) diet in that it lacks phytoestrogen-metabolizing bacteria. To investigate the effects of phytoestrogens on the microbiota inflammatory response and EAE disease severity we switched the diet of mice raised under a phyto-free (PF) diet to an isoflavone-rich diet. Microbiota analysis showed that the change in diet from one that is ISO to one that is PF reduces beneficial bacteria such as species. In addition we observed functional differences in lipopolysaccharide (LPS) biosynthesis pathways. Moreover LPS extracted from feces of mice fed an ISO diet induced increased production of anti-inflammatory cytokines from bone marrow-derived macrophages relative to fecal-LPS isolated from mice fed a PF diet. Eventually mice whose diet was switched from a PF diet to an ISO diet trended toward reduced EAE severity and mortality. Overall we show that an isoflavone-rich diet specifically modulates LPS biosynthesis of the gut microbiota imparts an anti-inflammatory response and decreases disease severity.
Topics: Animals; Cytokines; Diet; Encephalomyelitis, Autoimmune, Experimental; Gastrointestinal Microbiome; Inflammation; Isoflavones; Lipopolysaccharides; Mice; Mice, Inbred C57BL; Phytoestrogens
PubMed: 36179318
DOI: 10.1080/19490976.2022.2127446 -
Frontiers in Immunology 2022Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS. The etiology of MS is complex, and results from the interaction of multiple...
BACKGROUND
Multiple sclerosis (MS) is an inflammatory and demyelinating disease of the CNS. The etiology of MS is complex, and results from the interaction of multiple environmental and genetic factors. Although human leukocyte antigen-HLA alleles such as HLA-DR2 and -DR3 are considered the strongest genetic factors, the environmental factors responsible for disease predisposition are not well understood. Recently, diet and gut microbiota have emerged as an important environmental factors linked to the increased incidence of MS. Especially, western diets rich inprotein and fat have been linked to the increased incidence of obesity. Numerous clinical data indicate a role of obesity and gut microbiota in MS; however, the mechanistic link between gut microbiota and obesity in the pathobiology of MS remains unclear. The present study determines the mechanisms driving MS severity in the context of obesity utilizing a high-fat diet (HFD) induced obese HLA-DR3 class-II transgenic mouse model of MS.
METHODS
HLA-DR3 transgenic mice were kept on a standard HFD diet or Normal Chow (NC) for eight weeks. Gut microbiota composition and functional analysis were performed from the fecal DNA of mice. Experimental autoimmune encephalomyelitis-EAE (an animal model of MS) was induced by immunization with the proteolipid protein-PLP peptide in complete Freud's Adjuvant (CFA) and pertussis toxin.
RESULTS
We observed that HFD-induced obesity caused gut dysbiosis and severe disease compared to mice on NC. Amelioration of disease severity in mice depleted of gut microbiota suggested an important role of gut bacteria in severe EAE in obese mice. Fecal microbiota analysis in HFD mice shows gut microbiota alterations with an increase in the abundance of and bacteria and modulation of various bacterial metabolic pathways including bacterial hydrogen sulfide biosynthetic pathways. Finally, mice on HFD showed increased gut permeability and systemic inflammation suggesting a role gut barrier modulation in obesity induced disease severity.
CONCLUSIONS
This study provides evidence for the involvement of the gut microbiome and associated metabolic pathways plus gut permeability in obesity-induced modulation of EAE disease severity. A better understanding of the same will be helpful to identify novel therapeutic targets to reduce disease severity in obese MS patients.
Topics: Animals; Diet, High-Fat; Disease Models, Animal; Dysbiosis; Encephalomyelitis, Autoimmune, Experimental; HLA-DR2 Antigen; HLA-DR3 Antigen; Humans; Hydrogen Sulfide; Mice; Mice, Obese; Mice, Transgenic; Multiple Sclerosis; Obesity; Pertussis Toxin; Proteolipids; Severity of Illness Index
PubMed: 36164343
DOI: 10.3389/fimmu.2022.966417 -
Saudi Journal of Biological Sciences Jul 2022The diversity of oral microbiota is affected by diets habits, gender, age, ethnic group, and environment. The acquisition of oral microbiota and the role of family on...
The diversity of oral microbiota is affected by diets habits, gender, age, ethnic group, and environment. The acquisition of oral microbiota and the role of family on oral microbiota development is poorly understood. This study aims to characterize and compare the oral bacterial microbiota among families using 16S rRNA gene sequencing. This work was conducted in Jeddah city from 2020 to 2021, in which four families composed of 20 members of different ethnicity and lifestyle were recruited. After the collection of saliva samples, the DNA was extracted and processed for 16S rRNA gene metagenomics sequencing. Among 378 OUTs generated, 39 (10.3%) were unique in group A, 13 (3.4%) unique in group B, and 11 (2.9%) were unique in groups C and D. We observed a significant variation at the level of top abundance phylum (14), families (23), genera (24), and species (22) of bacteria among family members. Within family groups, different bacterial species were reported to be more dominant among certain family members than the other; and and were more dominant in parents of some families than the other family member. In summary, this study highlights the precise and perceptible association of oral microbial between family members. Our findings documented the clustering of certain bacterial species in family groups, supporting the role of community in the development of oral microbiota.
PubMed: 35677897
DOI: 10.1016/j.sjbs.2022.103317 -
Frontiers in Cellular and Infection... 2022Early childhood caries (ECC) is not only the most common chronic childhood disease but also disproportionately affects underserved populations. Of those, children living...
Early childhood caries (ECC) is not only the most common chronic childhood disease but also disproportionately affects underserved populations. Of those, children living in Thailand have been found to have high rates of ECC and severe ECC. Frequently, the cause of ECC is blamed on a handful of cariogenic organisms, such as and . However, ECC is a multifactorial disease that results from an ecological shift in the oral cavity from a neutral pH (~7.5) to an acidic pH (<5.5) environment influenced by the host individual's biological, socio-behavioral, and lifestyle factors. Currently, there is a lack of understanding of how risk factors at various levels influence the oral health of children at risk. We applied a statistical machine learning approach for multimodal data integration (parallel and hierarchical) to identify caries-related multiplatform factors in a large cohort of mother-child dyads living in Chiang Mai, Thailand (N=177). Whole saliva (1 mL) was collected from each individual for DNA extraction and 16S rRNA sequencing. A set of maternal and early childhood factors were included in the data analysis. Significantly, vaginal delivery, preterm birth, and frequent sugary snacking were found to increase the risk for ECC. The salivary microbial diversity was significantly different in children with ECC or without ECC. Results of linear discriminant analysis effect size (LEfSe) analysis of the microbial community demonstrated that , , and were significantly enriched in ECC children. Whereas was less abundant among caries-free children, suggesting its potential to be a candidate biomarker for good oral health. Based on the multimodal data integration and statistical machine learning models, the study revealed that the mode of delivery and snack consumption outrank salivary microbiome in predicting ECC in Thai children. The biological and behavioral factors may play significant roles in the microbial pathobiology of ECC and warrant further investigation.
Topics: Child, Preschool; Dental Caries; Dental Caries Susceptibility; Female; Humans; Infant, Newborn; Microbiota; Premature Birth; RNA, Ribosomal, 16S; Saliva; Snacks; Streptococcus mutans; Thailand
PubMed: 35677657
DOI: 10.3389/fcimb.2022.881899 -
PloS One 2022Trillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in...
Trillions of microbes such as bacteria, fungi, and viruses exist in the healthy human gut microbiome. Although gut bacterial dysbiosis has been extensively studied in multiple sclerosis (MS), the significance of the fungal microbiome (mycobiome) is an understudied and neglected part of the intestinal microbiome in MS. The aim of this study was to characterize the gut mycobiome of patients with relapsing-remitting multiple sclerosis (RRMS), compare it to healthy controls, and examine its association with changes in the bacterial microbiome. We characterized and compared the mycobiome of 20 RRMS patients and 33 healthy controls (HC) using Internal Transcribed Spacer 2 (ITS2) and compared mycobiome interactions with the bacterial microbiome using 16S rRNA sequencing. Our results demonstrate an altered mycobiome in RRMS patients compared with HC. RRMS patients showed an increased abundance of Basidiomycota and decreased Ascomycota at the phylum level with an increased abundance of Candida and Epicoccum genera along with a decreased abundance of Saccharomyces compared to HC. We also observed an increased ITS2/16S ratio, altered fungal and bacterial associations, and altered fungal functional profiles in MS patients compared to HC. This study demonstrates that RRMS patients had a distinct mycobiome with associated changes in the bacterial microbiome compared to HC. There is an increased fungal to bacterial ratio as well as more diverse fungal-bacterial interactions in RRMS patients compared to HC. Our study is the first step towards future studies in delineating the mechanisms through which the fungal microbiome can influence MS disease.
Topics: Ascomycota; Bacteria; Dysbiosis; Fungi; Humans; Multiple Sclerosis; Mycobiome; RNA, Ribosomal, 16S
PubMed: 35472144
DOI: 10.1371/journal.pone.0264556