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Gut Microbes 2021The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of... (Review)
Review
The functional diversity of the mammalian intestinal microbiome far exceeds that of the host organism, and microbial genes contribute substantially to the well-being of the host. However, beneficial gut organisms can also be pathogenic when present in the gut or other locations in the body. Among dominant beneficial bacteria are several species of , which metabolize polysaccharides and oligosaccharides, providing nutrition and vitamins to the host and other intestinal microbial residents. These topics and the specific organismal and molecular interactions that are known to be responsible for the beneficial and detrimental effects of species in humans comprise the focus of this review. The complexity of these interactions will be revealed.
Topics: Animals; Bacteroides; Extracellular Vesicles; Gastrointestinal Microbiome; Gastrointestinal Tract; Humans; Microbial Interactions; Polysaccharides; Virulence Factors
PubMed: 33535896
DOI: 10.1080/19490976.2020.1848158 -
Frontiers in Cellular and Infection... 2020Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a... (Review)
Review
Periodontal disease is a chronic infectious disease associated with a variety of bacteria, which can cause damage to the periodontal support structure and affect a variety of systemic system diseases such as cancer, cardiovascular disease, diabetes, rheumatoid arthritis, non-alcoholic fatty liver, and Alzheimer's disease. () is the most important pathogenic bacteria for periodontal disease. It can produce outer membrane vesicles (OMVs) and release them into the environment, playing an important role in its pathogenesis. This article focuses on OMVs, reviews its production and regulation, virulence components, mode of action and related diseases, with a view to providing new ideas for the prevention and treatment of diseases related to infections.
Topics: Humans; Periodontal Diseases; Porphyromonas gingivalis; Virulence; Virulence Factors
PubMed: 33585266
DOI: 10.3389/fcimb.2020.585917 -
Nutrients Feb 2023Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods:...
Ankylosing spondylitis (AS) is associated with a variety of gut microbiotas. We aim to analyze the causal relationship between the two at the genetic level. Methods: Mendelian randomization (MR) is a type of instrumental variables (IVs) analysis; MR follows the Mendelian genetic rule of "parental alleles are randomly assigned to offspring" and takes genetic variation as IVs to infer the causal association between exposure factors and study outcome in observational studies. Genome-wide association study (GWAS) summary data of AS were from the FinnGen consortium, and the gut microbiota (Bacteroides, Streptococcus, Proteobacteria, Lachnospiraceae) were from the MiBioGen consortium. The TwoSampleMR and MRPRESSO packages of the R were used to perform a two-sample MR study. Random-effects inverse variance weighted (IVW) was the main analysis method, and MR Egger, weighted median, simple mode, and weighted mode were used as supplementary methods. We examined heterogeneity and horizontal pleiotropy, and examined whether the analysis results were influenced by a single SNP. We applied radial variants of the IVW and MR-Egger model for the improved visualization of the causal estimate. We further examined the causal relationship between AS and gut microbiota, and the robustness of the analysis results. Finally, we performed maximum likelihood, penalized weighted median, and IVW (fixed effects) to further identify the potential causal association. The random-effects IVW results showed that Bacteroides ( = 0.965, OR 95% confidence interval [CI] = 0.990 [0.621-1.579]), Streptococcus ( = 0.591, OR 95% CI = 1.120 [0.741-1.692]), Proteobacteria ( = 0.522, OR 95% CI = 1.160 [0.737-1.826]), and Lachnospiraceae ( = 0.717, OR 95% CI = 1.073 [0.732-1.574]) have no genetic causal relationship with AS. There was no heterogeneity, horizontal pleiotropy or outliers, and results were normally distributed. The MR analysis results were not driven by a single SNP. This study showed that Bacteroides, Streptococcus, Proteobacteria and Lachnospiraceae, four common gut microbiotas associated with AS, had no causal relationship with AS at the genetic level. This study makes a positive contribution to the genetics of AS, but the insufficient number of gut microbiota included is a limitation.
Topics: Humans; Bacteroides; Clostridiales; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Polymorphism, Single Nucleotide; Proteobacteria; Spondylitis, Ankylosing
PubMed: 36839415
DOI: 10.3390/nu15041057 -
Nature Jun 2019Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing...
Individuals vary widely in their responses to medicinal drugs, which can be dangerous and expensive owing to treatment delays and adverse effects. Although increasing evidence implicates the gut microbiome in this variability, the molecular mechanisms involved remain largely unknown. Here we show, by measuring the ability of 76 human gut bacteria from diverse clades to metabolize 271 orally administered drugs, that many drugs are chemically modified by microorganisms. We combined high-throughput genetic analyses with mass spectrometry to systematically identify microbial gene products that metabolize drugs. These microbiome-encoded enzymes can directly and substantially affect intestinal and systemic drug metabolism in mice, and can explain the drug-metabolizing activities of human gut bacteria and communities on the basis of their genomic contents. These causal links between the gene content and metabolic activities of the microbiota connect interpersonal variability in microbiomes to interpersonal differences in drug metabolism, which has implications for medical therapy and drug development across multiple disease indications.
Topics: Animals; Bacteria; Bacteroides thetaiotaomicron; Diltiazem; Female; Gastrointestinal Microbiome; Genome, Bacterial; Germ-Free Life; Humans; Male; Mice; Pharmaceutical Preparations; Substrate Specificity
PubMed: 31158845
DOI: 10.1038/s41586-019-1291-3 -
Archives of Razi Institute Oct 2022Chronic periodontitis is an inflammatory disease of the dental plaque and affects the soft tissues supporting the tooth. It is one of the most practical oral health... (Review)
Review
Chronic periodontitis is an inflammatory disease of the dental plaque and affects the soft tissues supporting the tooth. It is one of the most practical oral health issues across the globe and adversely affects the quality of life. In a neutrophil-mediated action, the inflammatory response to periodontitis destroys the periodontal ligaments, gums, the alveolar bone, and the cementum. Some of the most associated invasive pathogens with periodontitis are , , and . Google Scholar and PubMed were used to search the evidence using key terms like 'periodontitis,' ',' 'Oral Dysbiosis and Periodontitis,' ' and Periodontitis,' etc. Only studies were included reviewing the and its role in periodontitis. It has been observed from several oral pathogens that has received immense attention due to a strong association between and periodontal disease. also disrupts the delicate balance between various members of the oral microbial communities and promotes oral dysbiosis. The dysbiotic state of the oral microbiome is distinct in functional capabilities and shows a higher expression of genes involved in lipopolysaccharide synthesis, energy regulation, and bacterial motility. Certain virulence factors such as gingipains, LPS, and fimbriae also increase the invasion and pathogenicity of . Its presence in the periodontal tissues increases the secretion of numerous pro-inflammatory mediators such as TNF-α, IL-8, and IL-1β, leading to the destruction of soft gingival tissues and ligaments. Early detection of periodontitis and immediate treatment can prevent soft tissue destruction and dentition loss. In conclusion, details about the oral microbiome, oral dysbiosis, and inflammation may offer new therapeutic options in the future, including a personalized approach and the use of combination therapy.
Topics: Dysbiosis; Inflammation; Periodontitis; Porphyromonas gingivalis; Quality of Life; Humans
PubMed: 37123122
DOI: 10.22092/ARI.2021.356596.1875 -
Nutrients Apr 2023The Mediterranean Diet (MD) is plant-based and consists of multiple daily portions of vegetables, fruit, cereals, and olive oil. Although there are challenges with... (Review)
Review
The Mediterranean Diet (MD) is plant-based and consists of multiple daily portions of vegetables, fruit, cereals, and olive oil. Although there are challenges with isolating the MD from the typical Mediterranean lifestyle and culture (including prolonged 'social' meals and siestas), much evidence supports the health benefits of the MD that include improved longevity, reduced metabolic risk of Diabetes Mellitus, obesity, and Metabolic Syndrome, reduced risk of malignancy and cardiovascular disease, and improved cognitive function. The MD is also associated with characteristic modifications to gut microbiota, mediated through its constituent parts (primarily dietary fibres, extra virgin olive oil, and polyunsaturated fatty acids [including ω-3]). These include enhanced growth of species that produce short-chain fatty acids (butyrate), such as and , enhanced growth of , , and species, and reduced growth of Firmicutes and species. Such changes in gut microbiota are known to be associated favourably with inflammatory and oxidative status, propensity for malignancy and overall metabolic health. A key challenge for the future is to explore the extent to which the health benefits of the MD are mediated by such changes to gut microbiota. The MD confers both health and environmental benefits. Adoption of the MD should perhaps be encouraged and facilitated more generally and not just restricted to populations from Mediterranean regions. However, there are key challenges to this approach that include limited perennial availability of the constituent parts of the MD in some non-Mediterranean regions, intolerability of a high-fibre diet for some people, and potential cultural disconnects that juxtapose some traditional (including Western) diets with the MD.
Topics: Humans; Gastrointestinal Microbiome; Diet, Mediterranean; Bacteroides; Bifidobacterium; Butyrates
PubMed: 37432307
DOI: 10.3390/nu15092150 -
Cell Host & Microbe Oct 2019The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in...
The human gut contains a vast array of viruses, mostly bacteriophages. The majority remain uncharacterized, and their roles in shaping the gut microbiome and in impacting on human health remain poorly understood. We performed longitudinal metagenomic analysis of fecal viruses in healthy adults that reveal high temporal stability, individual specificity, and correlation with the bacterial microbiome. Using a database-independent approach that uses most of the sequencing data, we uncovered the existence of a stable, numerically predominant individual-specific persistent personal virome. Clustering of viral genomes and de novo taxonomic annotation identified several groups of crAss-like and Microviridae bacteriophages as the most stable colonizers of the human gut. CRISPR-based host prediction highlighted connections between these stable viral communities and highly predominant gut bacterial taxa such as Bacteroides, Prevotella, and Faecalibacterium. This study provides insights into the structure of the human gut virome and serves as an important baseline for hypothesis-driven research.
Topics: Bacteroides; Faecalibacterium; Gastrointestinal Microbiome; Humans; Longitudinal Studies; Metagenome; Microviridae; Prevotella; Viral Load
PubMed: 31600503
DOI: 10.1016/j.chom.2019.09.009 -
International Journal of Oral Science Sep 2021Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a...
Ulcerative Colitis (UC) has been reported to be related to Porphyromonas gingivalis (P. gingivalis). Porphyromonas gingivalis peptidylarginine deiminase (PPAD), a virulence factor released by P. gingivalis, is known to induce inflammatory responses. To explore the pathological relationships between PPAD and UC, we used homologous recombination technology to construct a P. gingivalis strain in which the PPAD gene was deleted (Δppad) and a Δppad strain in which the PPAD gene was restored (comΔppad). C57BL/6 mice were orally gavaged with saline, P. gingivalis, Δppad, or comΔppad twice a week for the entire 40 days (days 0-40), and then, UC was induced by dextran sodium sulfate (DSS) solution for 10 days (days 31-40). P. gingivalis and comΔppad exacerbated DDS-induced colitis, which was determined by assessing the parameters of colon length, disease activity index, and histological activity index, but Δppad failed to exacerbate DDS-induced colitis. Flow cytometry and ELISA revealed that compared with Δppad, P. gingivalis, and comΔppad increased T helper 17 (Th17) cell numbers and interleukin (IL)-17 production but decreased regulatory T cells (Tregs) numbers and IL-10 production in the spleens of mice with UC. We also cocultured P. gingivalis, Δppad, or comΔppad with T lymphocytes in vitro and found that P. gingivalis and comΔppad significantly increased Th17 cell numbers and decreased Treg cell numbers. Immunofluorescence staining of colon tissue paraffin sections also confirmed these results. The results suggested that P. gingivalis exacerbated the severity of UC in part via PPAD.
Topics: Animals; Colitis, Ulcerative; Mice; Mice, Inbred C57BL; Porphyromonas gingivalis; Protein-Arginine Deiminases; Virulence Factors
PubMed: 34593756
DOI: 10.1038/s41368-021-00136-2 -
Cellular & Molecular Immunology Dec 2022Both preclinical and established rheumatoid arthritis (RA) patients display alterations in the gut microbiome. Prevotella spp. are preferentially enriched in a subset of...
Both preclinical and established rheumatoid arthritis (RA) patients display alterations in the gut microbiome. Prevotella spp. are preferentially enriched in a subset of RA patients. Here, we isolated a Prevotella strain, P. copri RA, from the feces of RA patients and showed that colonization of P. copri RA exacerbated arthritis in a collagen-induced arthritis (CIA) model. With the presence of P. copri RA colonization, a high-fiber diet exacerbated arthritis via microbial alterations and intestinal inflammation. Colonization of P. copri together with a high-fiber diet enabled the digestion of complex fiber, which led to the overproduction of organic acids, including fumarate, succinate and short-chain fatty acids. Succinate promoted proinflammatory responses in macrophages, and supplementation with succinate exacerbated arthritis in the CIA model. Our findings highlight the importance of dysbiosis when evaluating the effects of dietary interventions on RA pathogenesis and provide new insight into dietary interventions or microbiome modifications to improve RA management.
Topics: Animals; Humans; Prevotella; Arthritis, Rheumatoid; Arthritis, Experimental; Diet; Succinates
PubMed: 36323929
DOI: 10.1038/s41423-022-00934-6 -
Cell Host & Microbe Nov 2019Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting...
Prevotella copri is a common human gut microbe that has been both positively and negatively associated with host health. In a cross-continent meta-analysis exploiting >6,500 metagenomes, we obtained >1,000 genomes and explored the genetic and population structure of P. copri. P. copri encompasses four distinct clades (>10% inter-clade genetic divergence) that we propose constitute the P. copri complex, and all clades were confirmed by isolate sequencing. These clades are nearly ubiquitous and co-present in non-Westernized populations. Genomic analysis showed substantial functional diversity in the complex with notable differences in carbohydrate metabolism, suggesting that multi-generational dietary modifications may be driving reduced prevalence in Westernized populations. Analysis of ancient metagenomes highlighted patterns of P. copri presence consistent with modern non-Westernized populations and a clade delineation time pre-dating human migratory waves out of Africa. These findings reveal that P. copri exhibits a high diversity that is underrepresented in Western-lifestyle populations.
Topics: Diet; Ethiopia; Feces; Fossils; Gastrointestinal Microbiome; Genetic Variation; Genome, Bacterial; Ghana; Humans; Prevotella; Tanzania
PubMed: 31607556
DOI: 10.1016/j.chom.2019.08.018