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Frontiers in Microbiology 2023The importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent...
Metagenomic signatures reveal the key role of phloretin in amelioration of gut dysbiosis attributed to metabolic dysfunction-associated fatty liver disease by time-dependent modulation of gut microbiome.
The importance of gut-liver axis in the pathophysiology of metabolic dysfunction-associated fatty liver disease (MAFLD) is being investigated more closely in recent times. However, the inevitable changes in gut microbiota during progression of the disease merits closer look. The present work intends to assess the time-dependent gut dysbiosis in MAFLD, its implications in disease progression and role of plant-derived prebiotics in its attenuation. Male C57BL/6J mice were given western diet (WD) for up to 16 weeks and phloretin was administered orally. The fecal samples of mice were collected every fourth week for 16 weeks. The animals were sacrificed at the end of the study and biochemical and histological analyses were performed. Further, 16S rRNA amplicon sequencing analysis was performed to investigate longitudinal modification of gut microbiome at different time points. Findings of our study corroborate that phloretin alleviated the metabolic changes and mitigated circulating inflammatory cytokines levels. Phloretin treatment resists WD induced changes in microbial diversity of mice and decreased endotoxin content. Prolonged exposure of WD changed dynamics of gut microbiota abundance and distribution. Increased abundance of pathogenic taxa like , and was noted. Phloretin treatment not only reversed this dysbiosis but also modulated taxonomic signatures of beneficial microbes like , , and . Therefore, the potential of phloretin to restore gut eubiosis could be utilized as an intervention strategy for the prevention of MAFLD and related metabolic disorders.
PubMed: 37744933
DOI: 10.3389/fmicb.2023.1210517 -
BioRxiv : the Preprint Server For... Aug 2023The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions....
BACKGROUND
The vaginal microbiome (VMB) has been classified into several discrete community state types, some of which have been associated with adverse human health conditions. However, the roles of the many vaginal bacteria in modulating the VMB and health remain unclear.
METHODS
The associations among the vaginal taxa and other vaginal taxa, the vaginal pH, and the host gene expression responses were determined by calculating the correlation among the relative abundance of the vaginal taxa, the association between the vaginal pH and the predominant taxon in the VMB, and the correlation between the relative abundance of the vaginal taxa and human gene expression at the transcriptional level, respectively. Using these associations, an alternative more informative method, the biological vagitype (BVT), is proposed to classify community state types of the VMB.
FINDINGS
Most spp., with the exception of , show significant correlations with host gene expression profiles and negative associations with dysbiosis-associated vaginal taxa. Many non- spp. exhibit varied correlations with spp., the vaginal pH, and host gene expression. Compared to other dysbiotic taxa, including Lachnocurva vaginae, has a stronger positive correlation with vaginal pH and a stronger negative correlation with spp. Most dysbiosis-associated taxa are associated with stress responses of the host at the transcriptional level, but the genus has a uniquely strong positive correlation with host immune responses. The association between BVTs of the VMBs and host characteristics, e.g., race/ethnicity, microbial infection, smoking, antibiotics, high blood pressure, economic state, diet, and others, was examined. The BVT classification method improved overall performance in associating specific vaginal microbial populations with host characteristics and phenotypes.
INTERPRETATION
This study sheds light on the biological characteristics of the vaginal microbiota, including some less abundant or still unculturable taxa. Since the BVT method was established based on these biological characteristics, the classification outcome of the VMB may have more clinical relevance. Because the BVT method performs better in associating specific vaginal community types with diseases, e.g., bacterial vaginosis and gonorrhea, it could be beneficial for the predictive modeling of adverse health.
FUNDING
This work was supported by grants [UH3AI083263, U54HD080784, and R01HD092415] from the National Institutes of Health; and support from the [GAPPS BMGF PPB] grant from the Global Alliance to Prevent Prematurity and Stillbirth. We would also like to thank the Office of Research on Women's Health at NIH for their generous support.
RESEARCH IN CONTEXT
The vaginal microbiome (VMB) refers to the community of microorganisms in the female lower reproductive tract. The VMB is often a simple ecosystem dominated by a single species. The most predominant bacteria in the VMB include several species and two non- species, i.e., Lachnocurva vaginae and species produce lactic acid to lower the vaginal pH and inhibit the growth of disease-associated bacteria. Thus, the predominance of protective Lactobacilli, i.e., , and , in the VMB is associated with overall vaginal health. However, the role of in promoting a healthy vaginal ecosystem is less clear. Actually, the biological and health relevance of many bacteria in the female lower reproductive tract is largely unknown. Some bacteria have low relative abundances, e.g., and spp.; and others are not yet culturable, e.g., Lachnocurva vaginae and BVAB TM7. When abundance of a taxon is low, its association with a host characteristic is a challenge. Previous methods to classify the VMB were based simply on their microbial compositions, and the biological characteristics of the vaginal bacteria were largely ignored. Thus, classification of these VMBs into biologically relevant community types, as described herein, should be helpful in determining their relevance to women's reproductive health. This study examines three biological characteristics of bacteria in the VMB, i.e., the associations among different bacterial taxa, the vaginal pH, and the host response. Based on these three characteristics, the influence of these bacteria, particularly low abundant and unculturable bacteria, on vaginal health is evaluated. seems to be neutral in maintaining overall vaginal health. is apparently more easily inhibited by spp. than Lachnocurva vaginae because of its stronger positive correlation with vaginal pH and negative correlation with . The genus of has a unique positive correlation with local immune responses, implying a role for in promoting inflammation. Compared with previous methods to classify the VMB, a new method, considering the above three biological characteristics of bacteria in the VMB, has been established. The new method performs better in associating specific vaginal communities with host characteristics and phenotypes; e.g., bacterial vaginosis and gonorrhea. Accurate biological classification of the VMB is fundamental for assessing its impact on women's health. Our classification scheme represents a step further toward that correct classification, eventually leading to new strategies for clinical assessment of the potential use of the VMB to diagnose or predict women's reproductive health.
PubMed: 37645743
DOI: 10.1101/2023.08.16.553525 -
Microorganisms Aug 2023Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community... (Review)
Review
Globally, colorectal cancer (CRC) is the second most common cause of mortality worldwide. Considerable evidence indicates that dysbiosis of the gut microbial community and its metabolite secretions play a fundamental role in advanced adenoma (ADA) and CRC development and progression. This study is a systematic review that aims to assess the clinical association between gut microbial markers and/or gut and circulating metabolites with ADA and CRC. Five electronic databases were searched by four independent reviewers. Only controlled trials that compared ADA and/or CRC with healthy control (HC) using either untargeted (16s rRNA gene or whole genome sequencing) or targeted (gene-based real-time PCR) identification methods for gut microbiome profile, or untargeted or targeted metabolite profiling approaches from the gut or serum/plasma, were eligible. Three independent reviewers evaluated the quality of the studies using the . Twenty-four studies were eligible. We identified strong evidence of two microbial markers and for ADA vs. CRC, and nine microbial markers -Lachnoclostridium, -Ruminococcus, spp., , Enterobacteriaceae, spp., Bacteroides, -, spp.-, , and for CRC vs. HC. The remaining metabolite marker evidence between the various groups, including ADA vs. HC, ADA vs. HC, and CRC vs. HC, was not of sufficient quality to support additional findings. The identified gut microbial markers can be used in a panel for diagnosing ADA and/or CRC. Further research in the metabolite markers area is needed to evaluate the possibility to use in diagnostic or prognostic markers for colorectal cancer.
PubMed: 37630597
DOI: 10.3390/microorganisms11082037 -
Pathogens (Basel, Switzerland) Jul 2023Areca nut and slaked lime, with or without tobacco wrapped in leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across... (Review)
Review
Areca nut and slaked lime, with or without tobacco wrapped in leaf, prepared as betel quid, is extensively consumed as a masticatory product in many countries across the world. Betel Quid can promote the malignant transformation of oral lesions as well as trigger benign cellular and molecular changes. In the oral cavity, it causes changes at the compositional level in oral microbiota called dysbiosis. This dysbiosis may play an important role in Oral Cancer in betel quid chewers. The abnormal presence and increase of bacteria , , , sp., , and in saliva and/or other oral sites of the cancer patients has attracted frequent attention for its association with oral cancer development. In the present review, the authors have analysed the literature reports to revisit the oncogenic potential of betel quid and oral microbiome alterations, evaluating the potential of oral microbiota both as a driver and biomarker of oral cancer. The authors have also shared a perspective that the restoration of local microbiota can become a potentially therapeutic or prophylactic strategy for the delay or reversal of lip and oral cavity cancers, especially in high-risk population groups.
PubMed: 37623956
DOI: 10.3390/pathogens12080996 -
Acta Bio-medica : Atenei Parmensis Aug 2023Corynebacterium or diphtheroid's are gram-positive aerobic, pleomorphic skin and mucosal membrane components that are not pathogenic in nature. Peptostreptococcus...
Corynebacterium or diphtheroid's are gram-positive aerobic, pleomorphic skin and mucosal membrane components that are not pathogenic in nature. Peptostreptococcus indolicus belongs to the Peptostreptococcus genus and is a Gram-Positive Anaerobic Cocci (GPAC). Less than one percent of endocarditis is caused by gram-positive anaerobic bacteria. We report the first case of Peptoniphilus indolicus and Corynebacterium endocarditis in a patient with native valves and a pacemaker. In time, diagnosis of a Peptoniphilus indolicus infection can lead to early management of the infection and a decreased incidence of serious complications such as embolization or abscess formation. The combination of aggressive antibiotic administration and surgical intervention can significantly decrease morbidity and mortality. This case report will highlight the importance of Peptoniphilus infective endocarditis, ultimately leading to better diagnostic strategies and management.
Topics: Humans; Endocarditis; Endocarditis, Bacterial; Corynebacterium; Embolization, Therapeutic
PubMed: 37606054
DOI: 10.23750/abm.v94iS1.14614 -
Sexual Medicine Aug 2023The loop electrosurgical excision procedure (LEEP) to treat cervical dysplasia (CD) is known to alter the cervical microbiota, the community of bacteria that play a...
BACKGROUND
The loop electrosurgical excision procedure (LEEP) to treat cervical dysplasia (CD) is known to alter the cervical microbiota, the community of bacteria that play a central role in female genital health. Perturbations to the microbiota of the female urogenital tract (FUT), including the urethra, vagina, and cervix, have been linked with symptoms of sexual dysfunction (SD), though correlations among LEEP, the microenvironment, and SD have not yet been described.
AIMS
To characterize the FUT microbiota before and after LEEP and investigate possible associations with SD.
METHODS
Females undergoing LEEP for CD were recruited to participate in the study. Urinary samples and vaginal and cervical swabs were collected immediately before and 3 months after treatment. Bacterial communities were characterized by 16S rRNA next-generation sequencing. Self-report surveys assessing demographics, medical history, and sexual function were completed at the same intervals.
OUTCOMES
Microbiota taxonomy and Female Sexual Function Index (FSFI) scores.
RESULTS
Alpha diversity revealed a significant decrease in species richness in the FUT microbiota post-LEEP. Beta diversity demonstrated significant differences among the cervical, urinary, and vaginal microenvironments pre- and post-LEEP. spp were the dominant microbial genus in the cervical microenvironment pre- and post-LEEP. Although the vaginal and urinary microenvironments were characterized by pre-LEEP, they were colonized by post-LEEP. Following LEEP, some participants experienced a significant increase in proinflammatory bacteria, including the genera , , , , and Others experienced significant decreases in inflammatory and protective bacteria post-LEEP, including , , , and Overall there were no significant changes in pre- and post-LEEP FSFI scores. However, post-LEEP FSFI scores were seemingly associated with changes in inflammatory bacteria in some participants.
CLINICAL IMPLICATIONS
There is an overall reduction in FUT microbiota dysbiosis post-LEEP. However, we show variability as some participants experienced persistent dysbiosis of FUT microbiota and elevated FSFI scores, suggesting that therapies to treat dysbiosis of FUT microbiota may reduce FSFI scores, thereby improving SD symptoms.
STRENGTHS AND LIMITATIONS
We demonstrate novel associations among urogenital sites, microbiota changes, LEEP, and SD. The small sample size and inability of species classification are limitations.
CONCLUSION
Diverse inflammatory microbiota characterizes CD in the FUT, and LEEP mostly returns microenvironments to a healthy state. However, some participants have persistent inflammatory bacteria post-LEEP, suggesting a non-uniform healing response. This study provides an impetus for future longitudinal studies to monitor and restore FUT microenvironments post-LEEP, aimed at mitigating postoperative SD symptoms.
PubMed: 37588087
DOI: 10.1093/sexmed/qfad039 -
ACS Infectious Diseases Sep 2023Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However,...
Changes in the oral microbiome are associated with oral squamous cell carcinoma (OSCC). Oral microbe-derived signatures have been utilized as markers of OSCC. However, the structure of the oral microbiome during OSCC recurrence and biomarkers for the prediction of OSCC recurrence remains unknown. To identify OSCC recurrence-associated microbial biomarkers for the prediction of OSCC recurrence, we performed 16S rRNA amplicon sequencing on 54 oral swab samples from OSCC patients. Differences in bacterial compositions were observed in patients with vs without recurrence. We found that , , , , , , , , and were enriched in OSCC recurrence. Functional analysis of the oral microbiome showed altered functions associated with OSCC recurrence compared with nonrecurrence. A random forest prediction model was constructed with five microbial signatures including , , , , and to discriminate OSCC recurrence from original OSCC (accuracy = 0.963). Moreover, we validated the prediction model in another independent cohort (46 OSCC patients), achieving an accuracy of 0.761. We compared the accuracy of the prediction of OSCC recurrence between the five microbial signatures and two clinicopathological parameters, including resection margin and lymph node counts. The results predicted by the model with five microbial signatures showed a higher accuracy than those based on the clinical outcomes from the two clinicopathological parameters. This study demonstrated the validity of using recurrence-related microbial biomarkers, a noninvasive and effective method for the prediction of OSCC recurrence. Our findings may contribute to the prognosis and treatment of OSCC recurrence.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Squamous Cell Carcinoma of Head and Neck; RNA, Ribosomal, 16S; Biomarkers; Head and Neck Neoplasms
PubMed: 37565768
DOI: 10.1021/acsinfecdis.3c00269 -
Frontiers in Microbiology 202316S rRNA is the universal gene of microbes, and it is often used as a target gene to obtain profiles of microbial communities via next-generation sequencing (NGS)...
16S rRNA is the universal gene of microbes, and it is often used as a target gene to obtain profiles of microbial communities via next-generation sequencing (NGS) technology. Traditionally, sequences are clustered into operational taxonomic units (OTUs) at a 97% threshold based on the taxonomic standard using 16S rRNA, and methods for the reduction of sequencing errors are bypassed, which may lead to false classification units. Several denoising algorithms have been published to solve this problem, such as DADA2 and Deblur, which can correct sequencing errors at single-nucleotide resolution by generating amplicon sequence variants (ASVs). As high-resolution ASVs are becoming more popular than OTUs and only one analysis method is usually selected in a particular study, there is a need for a thorough comparison of OTU clustering and denoising pipelines. In this study, three of the most widely used 16S rRNA methods (two denoising algorithms, DADA2 and Deblur, along with OTU clustering) were thoroughly compared using 16S rRNA amplification sequencing data generated from 358 clinical stool samples from the Colorectal Cancer (CRC) Screening Cohort. Our findings indicated that all approaches led to similar taxonomic profiles (with > 0.05 in PERMNAOVA and <0.001 in the Mantel test), although the number of ASVs/OTUs and the alpha-diversity indices varied considerably. Despite considerable differences in disease-related markers identified, disease-related analysis showed that all methods could result in similar conclusions. , and were identified by all three methods as enriched in the CRC group, while , and were identified by all three methods as enriched in the healthy group. In addition, disease-diagnostic models generated using machine learning algorithms based on the data from these different methods all achieved good diagnostic efficiency (AUC: 0.87-0.89), with the model based on DADA2 producing the highest AUC (0.8944 and 0.8907 in the training set and test set, respectively). However, there was no significant difference in performance between the models ( >0.05). In conclusion, this study demonstrates that DADA2, Deblur, and OTU clustering display similar power levels in taxa assignment and can produce similar conclusions in the case of the CRC cohort.
PubMed: 37560524
DOI: 10.3389/fmicb.2023.1178744 -
Molecular Oncology May 2024Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28...
Oral and intestinal samples from a cohort of 93 colorectal cancer (CRC) patients and 30 healthy controls (non-CRC) were collected for microbiome analysis. Saliva (28 non-CRC and 94 CRC), feces (30 non-CRC and 97 CRC), subgingival fluid (20 CRC), and tumor tissue samples (20 CRC) were used for 16S metabarcoding and/or RNA sequencing (RNAseq) approaches. A differential analysis of the abundance, performed with the ANCOM-BC package, adjusting the P-values by the Holm-Bonferroni method, revealed that Parvimonas was significantly over-represented in feces from CRC patients (P-value < 0.001) compared to healthy controls. A total of 11 Parvimonas micra isolates were obtained from the oral cavity and adenocarcinoma of CRC patients. Genome analysis identified a pair of isolates from the same patient that shared 99.2% identity, demonstrating that P. micra can translocate from the subgingival cavity to the gut. The data suggest that P. micra could migrate in a synergistic consortium with other periodontal bacteria. Metatranscriptomics confirmed that oral bacteria were more active in tumor than in non-neoplastic tissues. We suggest that P. micra could be considered as a CRC biomarker detected in non-invasive samples such as feces.
Topics: Humans; Colorectal Neoplasms; Male; Female; Adenocarcinoma; Middle Aged; Aged; Mouth; Feces; RNA, Ribosomal, 16S; Gingiva; Saliva; Peptostreptococcus; Firmicutes
PubMed: 37558206
DOI: 10.1002/1878-0261.13506