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BMC Medical Genomics Oct 2023Epidemiological studies have indicated a potential link between the gut microbiome and autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH), primary...
BACKGROUND
Epidemiological studies have indicated a potential link between the gut microbiome and autoimmune liver disease (AILD) such as autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC). The relationship between the gut microbiome and autoimmune liver disease is still uncertain due to confounding variables. In our study, we aim to shed light on this relationship by employing a two-sample Mendelian randomization approach.
METHODS
We conducted a two-sample Mendelian randomization (MR) study using the R package "TwoSampleMR". The exposure data consisted of genetic variants associated with 194 bacterial traits obtained from the MiBioGen consortium. Summary statistics for AILD were obtained from the GWAS Catalog website. Furthermore, a series of sensitivity analyses were performed to validate the initial MR results.
RESULTS
There were two, four and three bacteria traits associated with an increased risk of AIH. PBC, and PSC respectively. In contrast, there were five, two and five bacteria traits associated with a decreased risk for AIH, PBC and PSC. Notably, the genus_Clostridium_innocuum_group showed a negative association with AIH (OR = 0.67, 95% CI: 0.49-0.93), and the genus_Actinomyces was found to be genetically associated with a decreased risk of PSC (OR = 0.62, 95% CI: 0.42-0.90).
CONCLUSIONS
Our study identified the causal impact of specific bacterial features on the risk of AILD subtypes. Particularly, the genus_Clostridium_innocuum_group and the genus_Actinomyces demonstrated significant protective effects against AIH and PSC respectively. These findings provide further support for the potential use of targeted probiotics in the management of AILD.
Topics: Humans; Liver Cirrhosis, Biliary; Gastrointestinal Microbiome; Mendelian Randomization Analysis; Cholangitis, Sclerosing; Liver Diseases; Hepatitis, Autoimmune
PubMed: 37789337
DOI: 10.1186/s12920-023-01670-0 -
Cell Oct 2023Patescibacteria, also known as the candidate phyla radiation (CPR), are a diverse group of bacteria that constitute a disproportionately large fraction of microbial dark...
Patescibacteria, also known as the candidate phyla radiation (CPR), are a diverse group of bacteria that constitute a disproportionately large fraction of microbial dark matter. Its few cultivated members, belonging mostly to Saccharibacteria, grow as epibionts on host Actinobacteria. Due to a lack of suitable tools, the genetic basis of this lifestyle and other unique features of Patescibacteira remain unexplored. Here, we show that Saccharibacteria exhibit natural competence, and we exploit this property for their genetic manipulation. Imaging of fluorescent protein-labeled Saccharibacteria provides high spatiotemporal resolution of phenomena accompanying epibiotic growth, and a transposon-insertion sequencing (Tn-seq) genome-wide screen reveals the contribution of enigmatic Saccharibacterial genes to growth on their hosts. Finally, we leverage metagenomic data to provide cutting-edge protein structure-based bioinformatic resources that support the strain Southlakia epibionticum and its corresponding host, Actinomyces israelii, as a model system for unlocking the molecular underpinnings of the epibiotic lifestyle.
Topics: Bacteria; Metagenome; Metagenomics; Phylogeny; Actinobacteria
PubMed: 37683634
DOI: 10.1016/j.cell.2023.08.017 -
Frontiers in Microbiology 2023Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS),...
BACKGROUND
Increasing evidence from observational studies and clinical experimentation has indicated a link between the gut microbiotas (GMs) and polycystic ovary syndrome (PCOS), however, the causality and direction of causality between gut microbiome and PCOS remains to be established.
METHODS
We conducted a comprehensive search of four databases-PubMed, Cochrane Library, Web of Science, and Embase up until June 1, 2023, and subjected the results to a meta-analysis. In this study, a bidirectional two-sample Mendelian randomization (MR) analysis was employed to investigate the impact of gut microbiota on polycystic ovary syndrome (PCOS). The genome-wide association study (GWAS) data for PCOS comprised 113,238 samples, while the GWAS data for gut microbiota were derived from the MiBioGen consortium, encompassing a total sample size of 18,340 individuals. As the largest dataset of its kind, this study represents the most comprehensive genome-wide meta-analysis concerning gut microbiota composition to date. Single nucleotide polymorphisms (SNPs) were selected as instrumental variables at various taxonomic levels, including Phylum, Class, Order, Family, and Genus. The causal associations between exposures and outcomes were assessed using four established MR methods. To correct for multiple testing, the false discovery rate (FDR) method was applied. The reliability and potential biases of the results were evaluated through sensitivity analysis and F-statistics.
RESULTS
The meta-analysis incorporated a total of 20 studies that met the criteria, revealing a close association between PCOS and specific gut microbiota species. As per the results from our MR analysis, we identified six causal associations between the gut microbiome and polycystic ovary syndrome (PCOS). At the genus level, (OR = 1.369, = 0.040), (OR = 1.548, = 0.027), and (OR = 1.488, = 0.028) were identified as risk factors for PCOS. Conversely, (OR = 0.723, = 0.040), (OR = 0.580, = 0.032), and (OR = 0.732, = 0.030) were found to be protective factors against PCOS. Furthermore, the MR-PRESSO global test and MR-Egger regression indicated that our study results were not affected by horizontal pleiotropy ( > 0.05). Finally, the leave-one-out analysis corroborated the robustness of the MR findings.
CONCLUSION
Both our meta-analysis and MR study indicates that there is a causal relationship between the gut microbiome and PCOS, which may contribute to providing novel insights for the development of new preventive and therapeutic strategies for PCOS.
PubMed: 37555058
DOI: 10.3389/fmicb.2023.1203902 -
Microorganisms Jan 2024Dental caries is a significant oral and public health problem worldwide, especially in low-income populations. The risk of dental caries increases with frequent intake... (Review)
Review
Dental caries is a significant oral and public health problem worldwide, especially in low-income populations. The risk of dental caries increases with frequent intake of dietary carbohydrates, including sugars, leading to increased acidity and disruption of the symbiotic diverse and complex microbial community of health. Excess acid production leads to a dysbiotic shift in the bacterial biofilm composition, demineralization of tooth structure, and cavities. Highly acidic and acid-tolerant species associated with caries include , , , , and species. The differences in microbiotas depend on tooth site, extent of carious lesions, and rate of disease progression. Metagenomics and metatranscriptomics not only reveal the structure and genetic potential of the caries-associated microbiome, but, more importantly, capture the genetic makeup of the metabolically active microbiome in lesion sites. Due to its multifactorial nature, caries has been difficult to prevent. The use of topical fluoride has had a significant impact on reducing caries in clinical settings, but the approach is costly; the results are less sustainable for high-caries-risk individuals, especially children. Developing treatment regimens that specifically target and other acidogenic bacteria, such as using nanoparticles, show promise in altering the cariogenic microbiome, thereby combatting the disease.
PubMed: 38257948
DOI: 10.3390/microorganisms12010121 -
Frontiers in Public Health 2023Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a commonly observed metabolic anomaly globally, and as of the present time, there's no recognized solution. There is an increasing body of evidence from numerous observational studies indicating a significant correlation between gut flora and metabolic disease progression, particularly in relation to T2DM. Despite this, the direct impact of gut microbiota on T2DM isn't fully understood yet.
METHODS
The summary statistical figures for intestinal microbiota were sourced from the MiBioGen consortium, while the summary statistical data for T2DM were gathered from the Genome-Wide Association Studies (GWAS) database. These datasets were used to execute a two-sample Mendelian randomization (MR) investigation. The Inverse Variance Weighted (IVW), Maximum Likelihood, MR-Egger, Weighted Median, and Weighted Models strategies were employed to assess the impact of gut microbiota on T2DM. Findings were primarily obtained using the IVW technique. Techniques like MR-Egger were employed to identify the occurrence of horizontal pleiotropy among instrumental variables. Meanwhile, Cochran's Q statistical measures were utilized to assess the variability or heterogeneity within these instrumental variables.
RESULTS
The outcomes from the IVW analysis demonstrated that the genus (OR = 0.998, 95% confidence interval: 0.996-1.000, and = 0.038), genus (OR = 0.998, 95% confidence interval: 0.997-0.999, = 0.033), genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 3.78 × 10), and genus (OR = 0.995, 95% confidence interval: 0.993-0.998, = 8.08 × 10) all acted as defense elements against type 2 diabetes. Family (OR = 1.003, 95% confidence interval: 1.001-1.005, = 0.012), family (OR = 1.0025, 95% confidence interval: 1.000-1.005, = 0.043), genus (OR = 1.003,95% confidence interval: 1.001-1.005, = 4.38 × 10), genus (OR = 1.001,95% confidence interval: 1.000-1.002 = 0.012) were risk factors for type 2 diabetes. False Discovery Rate correction was performed with finding that genus., genus, family and T2DM no longer displayed a significant causal association. In addition, no significant heterogeneity or horizontal pleiotropy was found for instrumental variable.
CONCLUSION
This MR study relies on genetic variation tools to confirm the causal effect of genus , genus , family , genus and genus on T2DM in the gut microbiome, providing new directions and strategies for the treatment and early screening of T2DM, which carries significant clinical relevance. To develop new biomarkers and better understand targeted prevention strategies for T2DM, further comprehensive investigations are required into the protective and detrimental mechanisms exerted by these five genera against T2DM.
Topics: Humans; Clinical Relevance; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Genome-Wide Association Study; Risk Factors; Mendelian Randomization Analysis
PubMed: 37808975
DOI: 10.3389/fpubh.2023.1255059 -
Molecules (Basel, Switzerland) Aug 2023Actinomycetes inhabit both terrestrial and marine ecosystems and are highly proficient in producing a wide range of natural products with diverse biological functions,... (Review)
Review
Actinomycetes inhabit both terrestrial and marine ecosystems and are highly proficient in producing a wide range of natural products with diverse biological functions, including antitumor, immunosuppressive, antimicrobial, and antiviral activities. In this review, we delve into the life cycle, ecology, taxonomy, and classification of actinomycetes, as well as their varied bioactive metabolites recently discovered between 2015 and 2023. Additionally, we explore promising strategies to unveil and investigate new bioactive metabolites, encompassing genome mining, activation of silent genes through signal molecules, and co-cultivation approaches. By presenting this comprehensive and up-to-date review, we hope to offer a potential solution to uncover novel bioactive compounds with essential activities.
Topics: Actinobacteria; Actinomyces; Ecosystem; Anti-Infective Agents; Biological Products
PubMed: 37570885
DOI: 10.3390/molecules28155915 -
Antibiotics (Basel, Switzerland) Aug 2023Bovine mastitis is a polymicrobial disease characterised by inflammation of the udders of dairy and beef cattle. The infection has huge implications to health and... (Review)
Review
Bovine mastitis is a polymicrobial disease characterised by inflammation of the udders of dairy and beef cattle. The infection has huge implications to health and welfare of animals, impacting milk and beef production and costing up to EUR 32 billion annually to the dairy industry, globally. Bacterial communities associated with the disease include representative species from , , , , , , and . Conventional treatment relies on antibiotics, but antimicrobial resistance, declining antibiotic innovations and biofilm production negatively impact therapeutic efficacy. Bacteriophages (phages) are viruses which effectively target and lyse bacteria with extreme specificity and can be a valuable supplement or replacement to antibiotics for bovine mastitis. In this review, we provide an overview of the etiology of bovine mastitis, the advantages of phage therapy over chemical antibiotics for the strains and research work conducted in the area in various model systems to support phage deployment in the dairy industry. We emphasise work on phage isolation procedures from samples obtained from mastitic and non-mastitic sources, characterisation and efficacy testing of single and multiple phages as standalone treatments or adjuncts to probiotics in various in vitro, ex vivo and in vivo bovine mastitis infection models. Furthermore, we highlight the areas where improvements can be made with focus on phage cocktail optimisation, formulation, and genetic engineering to improve delivery, stability, efficacy, and safety in cattle. Phage therapy is becoming more attractive in clinical medicine and agriculture and thus, could mitigate the impending catastrophe of antimicrobial resistance in the dairy sector.
PubMed: 37627727
DOI: 10.3390/antibiotics12081307 -
BMC Genomics Dec 2023Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital...
BACKGROUND
Actinomyces strains are commonly found as part of the normal microflora on human tissue surfaces, including the oropharynx, gastrointestinal tract, and female genital tract. Understanding the diversity and characterization of Actinomyces species is crucial for human health, as they play an important role in dental plaque formation and biofilm-related infections. Two Actinomyces strains ATCC 49340 and ATCC 51655 have been utilized in various studies, but their accurate species classification and description remain unresolved.
RESULTS
To investigate the genomic properties and taxonomic status of these strains, we employed both 16S rRNA Sanger sequencing and whole-genome sequencing using the Illumina HiSeq X Ten platform with PE151 (paired-end) sequencing. Our analyses revealed that the draft genome of Actinomyces acetigenes ATCC 49340 was 3.27 Mbp with a 68.0% GC content, and Actinomyces stomatis ATCC 51655 has a genome size of 3.08 Mbp with a 68.1% GC content. Multi-locus (atpA, rpoB, pgi, metG, gltA, gyrA, and core genome SNPs) sequence analysis supported the phylogenetic placement of strains ATCC 51655 and ATCC 49340 as independent lineages. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI), and average amino acid identity (AAI) analyses indicated that both strains represented novel Actinomyces species, with values below the threshold for species demarcation (70% dDDH, 95% ANI and AAI). Pangenome analysis identified 5,731 gene clusters with strains ATCC 49340 and ATCC 51655 possessing 1,515 and 1,518 unique gene clusters, respectively. Additionally, genomic islands (GIs) prediction uncovered 24 putative GIs in strain ATCC 49340 and 16 in strain ATCC 51655, contributing to their genetic diversity and potential adaptive capabilities. Pathogenicity analysis highlighted the potential human pathogenicity risk associated with both strains, with several virulence-associated factors identified. CRISPR-Cas analysis exposed the presence of CRISPR and Cas genes in both strains, indicating these strains might evolve a robust defense mechanism against them.
CONCLUSION
This study supports the classification of strains ATCC 49340 and ATCC 51655 as novel species within the Actinomyces, in which the name Actinomyces acetigenes sp. nov. (type strain ATCC 49340 = VPI D163E-3 = CCUG 34286 = CCUG 35339 ) and Actinomyces stomatis sp. nov. (type strain ATCC 51655 = PK606 = CCUG 33930) are proposed.
Topics: Humans; Female; Actinomyces; Phylogeny; Sequence Analysis, DNA; RNA, Ribosomal, 16S; Mouth; Nucleic Acid Hybridization; Nucleotides; DNA; DNA, Bacterial; Bacterial Typing Techniques; Fatty Acids
PubMed: 38049764
DOI: 10.1186/s12864-023-09831-2