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Microbiology Spectrum Aug 2022Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in... (Meta-Analysis)
Meta-Analysis
Colorectal cancer (CRC) is the second leading cause of cancer mortality worldwide. The dysbiotic gut microbiota and its metabolite secretions play a significant role in CRC development and progression. In this study, we identified microbial and metabolic biomarkers applicable to CRC using a meta-analysis of metagenomic datasets from diverse geographical regions. We used LEfSe, random forest (RF), and co-occurrence network methods to identify microbial biomarkers. Geographic dataset-specific markers were identified and evaluated using area under the ROC curve (AUC) scores and random effect size. Co-occurrence networks analysis showed a reduction in the overall microbial associations and the presence of oral pathogenic microbial clusters in CRC networks. Analysis of predicted metabolites from CRC datasets showed the enrichment of amino acids, cadaverine, and creatine in CRC, which were positively correlated with CRC-associated microbes (Peptostreptococcus stomatis, Gemella morbillorum, Bacteroides fragilis, spp., Fusobacterium nucleatum, Solobacterium moorei, and Clostridium symbiosum), and negatively correlated with control-associated microbes. Conversely, butyrate, nicotinamide, choline, tryptophan, and 2-hydroxybutanoic acid showed positive correlations with control-associated microbes ( < 0.05). Overall, our study identified a set of global CRC biomarkers that are reproducible across geographic regions. We also reported significant differential metabolites and microbe-metabolite interactions associated with CRC. This study provided significant insights for further investigations leading to the development of noninvasive CRC diagnostic tools and therapeutic interventions. Several studies showed associations between gut dysbiosis and CRC. Yet, the results are not conclusive due to cohort-specific associations that are influenced by genomic, dietary, and environmental stimuli and associated reproducibility issues with various analysis approaches. Emerging evidence suggests the role of microbial metabolites in modulating host inflammation and DNA damage in CRC. However, the experimental validations have been hindered by cost, resources, and cumbersome technical expertise required for metabolomic investigations. In this study, we performed a meta-analysis of CRC microbiota data from diverse geographical regions using multiple methods to achieve reproducible results. We used a computational approach to predict the metabolomic profiles using existing CRC metagenomic datasets. We identified a reliable set of CRC-specific biomarkers from this analysis, including microbial and metabolite markers. In addition, we revealed significant microbe-metabolite associations through correlation analysis and microbial gene families associated with dysregulated metabolic pathways in CRC, which are essential in understanding the vastly sporadic nature of CRC development and progression.
Topics: Biomarkers; Colorectal Neoplasms; Dysbiosis; Gastrointestinal Microbiome; Humans; Reproducibility of Results
PubMed: 35766483
DOI: 10.1128/spectrum.00013-22 -
Microbiome Apr 2019Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer... (Observational Study)
Observational Study
BACKGROUND
Gastrointestinal mucosal injury (mucositis), commonly affecting the oral cavity, is a clinically significant yet incompletely understood complication of cancer chemotherapy. Although antineoplastic cytotoxicity constitutes the primary injury trigger, the interaction of oral microbial commensals with mucosal tissues could modify the response. It is not clear, however, whether chemotherapy and its associated treatments affect oral microbial communities disrupting the homeostatic balance between resident microorganisms and the adjacent mucosa and if such alterations are associated with mucositis. To gain knowledge on the pathophysiology of oral mucositis, 49 subjects receiving 5-fluorouracil (5-FU) or doxorubicin-based chemotherapy were evaluated longitudinally during one cycle, assessing clinical outcomes, bacterial and fungal oral microbiome changes, and epithelial transcriptome responses. As a control for microbiome stability, 30 non-cancer subjects were longitudinally assessed. Through complementary in vitro assays, we also evaluated the antibacterial potential of 5-FU on oral microorganisms and the interaction of commensals with oral epithelial tissues.
RESULTS
Oral mucositis severity was associated with 5-FU, increased salivary flow, and higher oral granulocyte counts. The oral bacteriome was disrupted during chemotherapy and while antibiotic and acid inhibitor intake contributed to these changes, bacteriome disruptions were also correlated with antineoplastics and independently and strongly associated with oral mucositis severity. Mucositis-associated bacteriome shifts included depletion of common health-associated commensals from the genera Streptococcus, Actinomyces, Gemella, Granulicatella, and Veillonella and enrichment of Gram-negative bacteria such as Fusobacterium nucleatum and Prevotella oris. Shifts could not be explained by a direct antibacterial effect of 5-FU, but rather resembled the inflammation-associated dysbiotic shifts seen in other oral conditions. Epithelial transcriptional responses during chemotherapy included upregulation of genes involved in innate immunity and apoptosis. Using a multilayer epithelial construct, we show mucositis-associated dysbiotic shifts may contribute to aggravate mucosal damage since the mucositis-depleted Streptococcus salivarius was tolerated as a commensal, while the mucositis-enriched F. nucleatum displayed pro-inflammatory and pro-apoptotic capacity.
CONCLUSIONS
Altogether, our work reveals that chemotherapy-induced oral mucositis is associated with bacterial dysbiosis and demonstrates the potential for dysbiotic shifts to aggravate antineoplastic-induced epithelial injury. These findings suggest that control of oral bacterial dysbiosis could represent a novel preventive approach to ameliorate oral mucositis.
Topics: Antineoplastic Agents; Bacteria; Drug Therapy; Drug-Related Side Effects and Adverse Reactions; Dysbiosis; Fluorouracil; Fungi; Humans; Inflammation; Longitudinal Studies; Microbiota; Mouth; Mouth Mucosa; Prospective Studies; Stomatitis
PubMed: 31018870
DOI: 10.1186/s40168-019-0679-5 -
Biomedicine & Pharmacotherapy =... Sep 2022To evaluate the effect of naringenin on improving PCOS and explore the mechanism.
PURPOSE
To evaluate the effect of naringenin on improving PCOS and explore the mechanism.
METHODS
Firstly, we carried out differential gene expression analysis from transcriptome sequencing data of human oocyte to screen the KEGG pathway, then the PCOS-like rat model was induced by letrozole. They were randomly divided into four groups: Normal group (N), PCOS group (P), Diane-35 group (D), and Naringenin group (Nar). The changes of estrus cycle, body weight, ovarian function, serum hormone levels, glucose metabolism, along with the expression of SIRT1, PGC-1ɑ, claudin-1 and occludin of the ovary and colon were investigated. Furthermore, the composition of the gut microbiome of fecal was tested.
RESULTS
By searching the KEGG pathway in target genes, we found that at least 15 KEGG pathways are significantly enriched in the ovarian function, such as AMPK signaling pathway, insulin secretion, and ovarian steroidogenesis. Interestingly, naringenin supplementation significantly reduced body weight, ameliorated hormone levels, improved insulin resistance, and mitigated pathological changes in ovarian tissue, up-regulated the expression of PGC-1ɑ, SIRT1, occludin and claudin-1 in colon. In addition, we also found that the abundance of Prevotella and Gemella was down-regulated, while the abundance of Butyricimonas, Lachnospira, Parabacteroides, Butyricicoccus, Streptococcus, Coprococcus was up-regulated.
CONCLUSION
Our data suggest that naringenin exerts a treatment PCOS effect, which may be related to the modulation of the gut microbiota and SIRT1/PGC-1ɑ signaling pathway. Our research may provide a new perspective for the treatment of PCOS and related diseases.
Topics: Animals; Body Weight; Claudin-1; Female; Flavanones; Gastrointestinal Microbiome; Hormones; Humans; Letrozole; Occludin; Polycystic Ovary Syndrome; Rats; Rats, Sprague-Dawley; Signal Transduction; Sirtuin 1
PubMed: 35724506
DOI: 10.1016/j.biopha.2022.113286 -
Journal of Clinical Microbiology Nov 2005More than 700 bacterial species or phylotypes, of which over 50% have not been cultivated, have been detected in the oral cavity. Our purposes were (i) to utilize... (Comparative Study)
Comparative Study
More than 700 bacterial species or phylotypes, of which over 50% have not been cultivated, have been detected in the oral cavity. Our purposes were (i) to utilize culture-independent molecular techniques to extend our knowledge on the breadth of bacterial diversity in the healthy human oral cavity, including not-yet-cultivated bacteria species, and (ii) to determine the site and subject specificity of bacterial colonization. Nine sites from five clinically healthy subjects were analyzed. Sites included tongue dorsum, lateral sides of tongue, buccal epithelium, hard palate, soft palate, supragingival plaque of tooth surfaces, subgingival plaque, maxillary anterior vestibule, and tonsils. 16S rRNA genes from sample DNA were amplified, cloned, and transformed into Escherichia coli. Sequences of 16S rRNA genes were used to determine species identity or closest relatives. In 2,589 clones, 141 predominant species were detected, of which over 60% have not been cultivated. Thirteen new phylotypes were identified. Species common to all sites belonged to the genera Gemella, Granulicatella, Streptococcus, and Veillonella. While some species were subject specific and detected in most sites, other species were site specific. Most sites possessed 20 to 30 different predominant species, and the number of predominant species from all nine sites per individual ranged from 34 to 72. Species typically associated with periodontitis and caries were not detected. There is a distinctive predominant bacterial flora of the healthy oral cavity that is highly diverse and site and subject specific. It is important to fully define the human microflora of the healthy oral cavity before we can understand the role of bacteria in oral disease.
Topics: Bacteria; Humans; Maxillary Sinus; Molecular Sequence Data; Mouth; Palatine Tonsil; Phylogeny; Polymerase Chain Reaction; RNA, Bacterial; RNA, Ribosomal, 16S; Species Specificity
PubMed: 16272510
DOI: 10.1128/JCM.43.11.5721-5732.2005 -
IDCases 2022We herein present the case presenting to our facility complaining of a fever of two months duration, who underwent dental procedure. Patient was diagnosed with infective...
We herein present the case presenting to our facility complaining of a fever of two months duration, who underwent dental procedure. Patient was diagnosed with infective endocarditis secondary to an uncommon bacteria: . Patient was found to have concomitant severe mitral valve regurgitation. Our patient did not have any comorbidity or risk factor beside his dental procedure. Our patient received intravenous antibiotic therapy for six weeks and was scheduled for mitral valve replacement.
PubMed: 36032179
DOI: 10.1016/j.idcr.2022.e01597 -
Journal of Oral Microbiology 2023species are core members of the human oral microbiome in healthy subjects and are regarded as commensals, although they can cause opportunistic infections. Our...
species are core members of the human oral microbiome in healthy subjects and are regarded as commensals, although they can cause opportunistic infections. Our objective was to evaluate the site-specialization of species among various habitats within the mouth by combining pangenomics and metagenomics. With pangenomics, we identified genome relationships and categorized genes as core and accessory to each species. With metagenomics, we identified the primary oral habitat of individual genomes. Our results establish that the genomes of three species, , and , are abundant and prevalent in human mouths at different oral sites: on buccal mucosa and keratinized gingiva; on tongue dorsum, throat, and tonsils; and in dental plaque. The gene-level basis of site-specificity was investigated by identifying genes that were core to genomes at a specific oral site but absent from other genomes. The riboflavin biosynthesis pathway was present in genomes associated with buccal mucosa but absent from the rest of the genomes. Overall, metapangenomics show that species have clear ecological preferences in the oral cavity of healthy humans and provides an approach to identifying gene-level drivers of site specificity.
PubMed: 37361319
DOI: 10.1080/20002297.2023.2225261 -
Polymers Aug 2022The oral microbiome can be shifted if the patients wear the acrylic retainers for a lengthy period. It is essential to understand the components of the plaque in order...
The oral microbiome can be shifted if the patients wear the acrylic retainers for a lengthy period. It is essential to understand the components of the plaque in order to forestall the development of dental caries and gingivitis. The aim of this study is to report the bacterial communities that adhere to the acrylic retainers by full-length nanopore 16S sequencing. Six healthy participants were allocated into 2 groups (chemical tablet and brushing groups). Plaque samples were collected from the acrylic retainer surfaces before and after cleaning. The bacterial communities were reported using full-length nanopore 16S sequencing. The results showed that 7 distinct phyla were identified by sequencing. The most prevalent of these was the Firmicutes. We found a total of 72 genera. The most common microorganism across all samples was Streptococcus, followed by Neisseria, Rothia, and Gemella. The beta diversity showed a significant difference between before and after cleaning (p < 0.05). This study revealed the novel finding that a combination of chemical and mechanical cleaning methods was the most effective method of eliminating retainer biofilms. Moreover, retainer cleaning tablets did not alter the homeostatic balance of the bacterial communities adhering to the acrylic retainers.
PubMed: 36080658
DOI: 10.3390/polym14173583 -
Scientific Reports Jan 2022Descriptions of the small intestinal microbiota are deficient and conflicting. We aimed to get a reliable description of the jejunal bacterial microbiota by...
Descriptions of the small intestinal microbiota are deficient and conflicting. We aimed to get a reliable description of the jejunal bacterial microbiota by investigating samples from two separate jejunal segments collected from the luminal mucosa during surgery. Sixty patients with morbid obesity selected for elective gastric bypass surgery were included in this survey. Samples collected by rubbing a swab against the mucosa of proximal and mid jejunal segments were characterized both quantitatively and qualitatively using a combination of microbial culture, a universal quantitative PCR and 16S deep sequencing. Within the inherent limitations of partial 16S sequencing, bacteria were assigned to the species level. By microbial culture, 53 patients (88.3%) had an estimated bacterial density of < 1600 cfu/ml in both segments whereof 31 (51.7%) were culture negative in both segments corresponding to a bacterial density below 160 cfu/ml. By quantitative PCR, 46 patients (76.7%) had less than 10 bacterial genomes/ml in both segments. The most abundant and frequently identified species by 16S deep sequencing were associated with the oral cavity, most often from the Streptococcus mitis group, the Streptococcus sanguinis group, Granulicatella adiacens/para-adiacens, the Schaalia odontolytica complex and Gemella haemolysans/taiwanensis. In general, few bacterial species were identified per sample and there was a low consistency both between the two investigated segments in each patient and between patients. The jejunal mucosa of fasting obese patients contains relatively few microorganisms and a core microbiota could not be established. The identified microbes are likely representatives of a transient microbiota and there is a high degree of overlap between the most frequently identified species in the jejunum and the recently described ileum core microbiota.
Topics: Adult; Aged; Bacteria; DNA, Bacterial; Female; Gastric Bypass; Gastrointestinal Microbiome; High-Throughput Nucleotide Sequencing; Humans; Intestinal Mucosa; Jejunum; Male; Middle Aged; Obesity, Morbid; Real-Time Polymerase Chain Reaction; Ribotyping; Young Adult
PubMed: 35102222
DOI: 10.1038/s41598-022-05723-9 -
Microbiology Spectrum Aug 2023Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite...
Metabolites and their interactions with microbiota may be involved in Helicobacter pylori-associated gastric lesion development. This study aimed to explore metabolite alterations upon H. pylori eradication and possible roles of microbiota-metabolite interactions in progression of precancerous lesions. Targeted metabolomics assays and 16S rRNA gene sequencing were conducted to investigate metabolic and microbial alterations of paired gastric biopsy specimens in 58 subjects with successful and 57 subjects with failed anti-H. pylori treatment. Integrative analyses were performed by combining the metabolomics and microbiome profiles from the same intervention participants. A total of 81 metabolites were significantly altered after successful eradication compared to failed treatment, including acylcarnitines, ceramides, triacylglycerol, cholesterol esters, fatty acid, sphingolipids, glycerophospholipids, and glycosylceramides, with values of <0.05 for all. The differential metabolites showed significant correlations with microbiota in baseline biopsy specimens, such as negative correlations between and glycerophospholipids, glycosylceramide, and triacylglycerol (0.05 for all), which were altered by eradication. The characteristic negative correlations between glycosylceramides and , Streptococcus, and in H. pylori-positive baseline biopsy specimens were further noticed in active gastritis and intestinal metaplasia (0.05 for all). A panel including differential metabolites, genera, and their interactions may help to discriminate high-risk subjects who progressed from mild to advanced precancerous lesions in short-term and long-term follow-up periods with areas under the curve (AUC) of 0.914 and 0.801, respectively. Therefore, our findings provide new insights into the metabolites and microbiota interactions in H. pylori-associated gastric lesion progression. In this study, a panel was established including differential metabolites, genera, and their interactions, which may help to discriminate high-risk subjects for progression from mild lesions to advanced precancerous lesions in short-term and long-term follow-up.
Topics: Humans; Helicobacter pylori; RNA, Ribosomal, 16S; Stomach Neoplasms; Helicobacter Infections; Microbiota; Precancerous Conditions
PubMed: 37358459
DOI: 10.1128/spectrum.05347-22 -
Cureus Nov 2023The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily... (Review)
Review
The gut microbiota is a community situated in the gastrointestinal tract that consists of bacteria thriving and contributing to the functions of our body. It is heavily influenced by what individuals eat, as the quality, amount, and frequency of food consumed can favor and inhibit specific bacteria. Type-2 diabetes mellitus (T2DM) is a common but detrimental condition that arises from excessive hyperglycemia, leading to either insulin resistance or damage to the B-cells that produce insulin in the pancreas. A poor diet high in sugar and fats leads to hyperglycemia, and as this persists, it can lead to the development of T2DM. Both insulin resistance and damage to B-cells are greatly affected by the diet an individual consumes, but is there a more involved relationship between the gut microbiota and T2DM? This paper aimed to evaluate the changes in the gut microbiota in patients with T2DM and the impacts of the changes in gut microbiota. and prevailed in patients with T2DM and healthy control, but their abundance varied greatly. There was also a significant decrease in bacteria like spp.and associated with insulin resistance. High levels of BMI in patients with T2DM have also been associated with increased levels of which has been associated with decreased fat metabolism and increased BMI. Metabolites such as butyrates and melatonin have also been identified as influencing the development and progression of T2DM. Testosterone levels have also been greatly influenced by the gut microbiota changes in T2DM, such that males with lower testosterone have a greater abundance of bacteria like and Identifying these changes and how they impact the body may lead to a treatment addressing insulin dysfunction and the changes that the altered gut microbiota leads to. Future research should address how treatment methods such as healthy diets, exercise, and anti-diabetics affect the gut microbiota and see if they influence sustained changes and reduced hyperglycemia.
PubMed: 38161953
DOI: 10.7759/cureus.49740