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Frontiers in Cellular and Infection... 2021The aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis.
BACKGROUND AND OBJECTIVES
The aim of this study was to examine the salivary microbiome in healthy peri-implant sites and those with peri-implantitis.
METHODS
Saliva samples were collected from 21 participants with healthy peri-implant sites and 21 participants with peri-implantitis. The V4 hypervariable region of the 16S rRNA gene was sequenced using the Ion Torrent PGM System (Ion 318™ Chip v2 400). The NGS analysis and composition of the salivary microbiome were determined by taxonomy assignment. Downstream bioinformatic analyses were performed in QIIME (v 1.9.1).
RESULTS
Clinical differences according to peri-implant condition status were found. Alpha diversity metrics revealed that the bacterial communities of participants with healthy peri-implant sites tended to have a richer microbial composition than individuals with peri-implantitis. In terms of beta diversity, bleeding on probing (BoP) may influence the microbial diversity. However, no clear partitioning was noted between the salivary microbiome of volunteers with healthy peri-implant sites or volunteers with peri-implantitis. The highest relative abundance of , and genus, and , , , , and was found in participants with peri-implantitis when compared with those with healthy peri-implant sites.
CONCLUSION
Differences in salivary microbiome composition were observed between patients with healthy peri-implant sites and those with peri-implantitis. BoP could affect the diversity (beta diversity) of the salivary microbiome.
Topics: Case-Control Studies; Dysbiosis; Humans; Microbiota; Peri-Implantitis; RNA, Ribosomal, 16S
PubMed: 35071026
DOI: 10.3389/fcimb.2021.696432 -
Transplantation and Cellular Therapy Jul 2022Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). MMF has a narrow therapeutic index, and...
Reduced Enterohepatic Recirculation of Mycophenolate and Lower Blood Concentrations Are Associated with the Stool Bacterial Microbiome after Hematopoietic Cell Transplantation.
Mycophenolate mofetil (MMF) is an important immunosuppressant used after allogeneic hematopoietic cell transplantation (HCT). MMF has a narrow therapeutic index, and blood concentrations of mycophenolic acid (MPA), the active component of MMF, are highly variable. Low MPA concentrations are associated with the risk of graft-versus-host disease (GVHD), whereas high concentrations are associated with toxicity. Reasons for variability are not well known and may include the presence of β-glucuronidase-producing bacteria in the gastrointestinal tract, which enhance MPA enterohepatic recirculation (EHR) by transforming MPA metabolites formed in the liver back to MPA. This study was conducted to determine whether individuals with high MPA EHR have a greater abundance of β-glucuronidase-producing bacteria in their stool and higher MPA concentrations compared with those with low EHR. We conducted a pharmacomicrobiomics study in 20 adult HCT recipients receiving a myeloablative or reduced-intensity preparative regimen. Participants received MMF 1 g i.v. every 8 hours with tacrolimus. Intensive pharmacokinetic sampling of MMF was conducted before hospital discharge; total MPA, MPA glucuronide (MPAG), and acyl-glucuronide metabolite (acylMPAG) were measured. EHR was defined as the ratio of MPA area under the concentration-versus-time curve (AUC) to MPA AUC. Differences in stool microbiome diversity and composition, determined by shotgun metagenomic sequencing, were compared above and below the median EHR (22%; range, 5% to 44%). The median EHR was 12% in the low EHR group and 29% in the high EHR group. MPA troughs, MPA AUC, and acyl-glucuronide metabolite (acylMPAG) AUC/AUC ratio were greater in the high EHR group compared with the low EHR group (1.53 μg/mL versus .28 μg/mL [P = .0001], 7.33 hour·μg/mL versus 1.79 hour·μg/mL [P = .0003], and .33 hour·μg/mL versus .24 hour·μg/mL [P = .0007], respectively). MPA AUC was greater in the high EHR group than in the low EHR group, and the difference trended toward significance (22.8 hour·μg/mL versus 15.3 hour·μg/mL; P = .06). Bacteroides vulgatus, Bacteroides stercoris, and Bacteroides thetaiotaomicron were 1.2- to 2.4-fold more abundant (P = .039, .024, and .046, respectively) in the high EHR group. MPA EHR was positively correlated with B. vulgatus (⍴ = .58; P ≤ .01) and B. thetaiotaomicron (⍴ = .46; P < .05) and negatively correlated with Blautia hydrogenotrophica (⍴ = -.53; P < .05). Therapeutic MPA troughs were achieved in 80% of patients in the high EHR group but in no patients in the low EHR group. There was a trend toward differences in MPA AUC and MPA concentration at steady-state (μg/mL) between the high EHR group versus the low EHR group (P = .06). MPA EHR was variable. Patients with high MPA EHR had greater abundance of Bacteroides species in stool and higher MPA exposure compared with patients with low MPA EHR. Therefore, Bacteroides may be protective against poor outcomes, such as graft-versus-host disease, in some patients but may increase the risk of MPA adverse effects in others. These data need to be confirmed and studied after oral MMF therapy.
Topics: Adult; Bacteria; Enzyme Inhibitors; Glucuronidase; Glucuronides; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Immunosuppressive Agents; Microbiota; Mycophenolic Acid
PubMed: 35489611
DOI: 10.1016/j.jtct.2022.04.018 -
BMC Infectious Diseases Oct 2021The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between...
BACKGROUND
The incidence of hand foot and mouth disease (HFMD) has increased in recent years, making it a very common childhood illness worldwide. The relationship between different enterovirus genotypes and disease severity is not clearly understood. Given that enteroviruses are transmitted through the gastrointestinal tract, we hypothesized that variation in intestinal microorganisms of the host might play a role in the prognosis of HFMD.
METHODS
We carried out a meta-transcriptomic-wide association study of fecal samples obtained from a cohort of children (254 patients, 227 tested positive for enterovirus, including 16 patients co-infectied with 2 kinds of enterovirus) with mild and severe HFMD and healthy controls.
RESULTS
We found there was no significant difference in the amount of each virus type between the mild and severe cases. Genes of enterovirus 71 (EV71) and coxsackievirus A (CV-A) from the severe and mild cases did not show significant clustering. Clostridium sp. L2-50 and Bacteroides stercoris ATCC 43183 were enriched in the guts of children with severe HFMD and KEGG enrichment was found between mild and severe cases.
CONCLUSIONS
Intestinal microorganisms appear to interact with enterovirus to determine the progression of HFMD. Genes of Bacteroides and Clostridium may be used as predictive markers for a more efficient prognosis and intervention. The enrichment of intestinal bacteria genes with functions may facilitate the development of severe symptoms for HFMD patients.
Topics: Bacteroides; Child; China; Enterovirus; Enterovirus A, Human; Gastrointestinal Microbiome; Hand, Foot and Mouth Disease; Humans; Infant
PubMed: 34645414
DOI: 10.1186/s12879-021-06748-7 -
Annals of Palliative Medicine Oct 2021Type 2 diabetes mellitus (T2DM) is a major social and public health problem which may be induced by intestinal flora imbalance through inflammatory response, and the...
BACKGROUND
Type 2 diabetes mellitus (T2DM) is a major social and public health problem which may be induced by intestinal flora imbalance through inflammatory response, and the specific mechanism remains unclear. In this study, we aim to explore the interaction network of intestinal flora and cell inflammation in T2DM.
METHODS
This a case-control study. Patients with T2DM was the case group and healthy people as control. The differences of cytokine expression levels between patients with T2DM and healthy controls were assessed by using flow cytometry. The diversity and abundance of intestinal flora were evaluated by using 16S rRNA three-generation full-length sequencing technology.
RESULTS
A total of 29 patients with T2DM and 28 healthy controls were included for analysis. Compared with the healthy control group, the expression levels of plasma cytokine interleukin-2 (IL-2) (P=0.0000006), IL-6 (P=0.000193), tumor necrosis factor α (TNF-α) (P=0.016), interferon-γ (IFN-γ) (P=0.000036) and interleukin-17 (IL-17) (P=0.004) were significantly up-regulated in T2DM patients, and the abundance of Megamonas_funiformis (P=0.0016) and Escherichia (P=0.049) in the intestine were significantly increased. In contrast, the abundance of Bacteroides_stercoris (P=0.0068), Bacteroides_uniformis (P=0.033), and Phascolarctobacterium_faecium (P=0.033) were decreased in T2DM patients. Further, differentially expressed Escherichia had a positive correlation with IFN-γ (r=0.73) by Pearson correlation analysis.
CONCLUSIONS
The interaction network between the intestinal bacteria Escherichia and the cytokine IFN-γ may drive inflammation in visceral adipose tissue (VAT), indicating insulin signal transduction can be inhibited in adipocytes to induce insulin resistance.
Topics: Case-Control Studies; Diabetes Mellitus, Type 2; Escherichia; Humans; Interferon-gamma; Intestines; RNA, Ribosomal, 16S
PubMed: 34763485
DOI: 10.21037/apm-21-2318 -
Frontiers in Microbiology 2020Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the...
Inflammatory bowel disease is associated with intestinal dysbiosis and with elevated antibody production toward microbial epitopes. The underlying processes linking the gut microbiota with inflammation are still unclear. Considering the constant induction of antibodies by gut microbial glycans, the aim of this study was to address whether the repertoire of carbohydrate-specific antibodies is altered in Crohn's disease or ulcerative colitis. IgG and IgM reactivities to oligosaccharides representative of mucosal glycans were tested in blood serum from 20 healthy control subjects, 17 ulcerative colitis patients, and 23 Crohn's disease patients using glycan arrays. An increased IgG and IgM reactivity toward fucosylated oligosaccharides was detected in Crohn's disease but not in ulcerative colitis. To address the antibody reactivity to the gut microbiota, IgG binding to members of a complex intestinal microbiota was measured and observed to be increased in sera of patients with Crohn's disease. Based on the elevated reactivity to fucosylated oligosaccharides, gut bacteria were tested for recognition by the fucose-binding lectin. was detected in IgG- and lectin-positive fractions and reactivity of lectin was demonstrated for additional species. IgG reactivity to these species was significantly increased in inflammatory bowel disease patients, indicating that the increased reactivity to fucosylated oligosaccharides detected in Crohn's disease may be induced by fucose-carrying intestinal bacteria. Enhanced antibody response to fucosylated epitopes may have systemic effects by altering the binding of circulating antibodies to endogenous glycoproteins.
PubMed: 32765449
DOI: 10.3389/fmicb.2020.01553 -
Brazilian Journal of Biology = Revista... 2021The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes...
The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .
Topics: Animals; Bacteroides; Bacteroidetes; Diabetes Mellitus, Type 2; Diet, High-Fat; Dysbiosis; Gastrointestinal Microbiome; Humans; Inflammation; Mice; Mice, Inbred C57BL; Prevotella; RNA, Ribosomal, 16S; Ruminococcus
PubMed: 34378656
DOI: 10.1590/1519-6984.242818 -
Microbiome Feb 2024Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS...
Chondroitin sulfate (CS) has widely been used as a symptomatic slow-acting drug or a dietary supplement for the treatment and prevention of osteoarthritis. However, CS could not be absorbed after oral intake due to its polyanionic nature and large molecular weight. Gut microbiota has recently been proposed to play a pivotal role in the metabolism of drugs and nutrients. Nonetheless, how CS is degraded by the human gut microbiota has not been fully characterized. In the present study, we demonstrated that each human gut microbiota was characterized with a unique capability for CS degradation. Degradation and fermentation of CS by the human gut microbiota produced significant amounts of unsaturated CS oligosaccharides (CSOSs) and short-chain fatty acids. To uncover which microbes were responsible for CS degradation, we isolated a total of 586 bacterial strains with a potential CS-degrading capability from 23 human fecal samples. Bacteroides salyersiae was a potent species for CS degradation in the human gut microbiota and produced the highest amount of CSOSs as compared to other well-recognized CS-degraders, including Bacteroides finegoldii, Bacteroides thetaiotaomicron, Bacteroides xylanisolvens, and Bacteroides ovatus. Genomic analysis suggested that B. salyersiae was armed with multiple carbohydrate-active enzymes that could potentially degrade CS into CSOSs. By using a spent medium assay, we further demonstrated that the unsaturated tetrasaccharide (udp4) produced by the primary degrader B. salyersiae could serve as a "public goods" molecule for the growth of Bacteroides stercoris, a secondary CS-degrader that was proficient at fermenting CSOSs but not CS. Taken together, our study provides insights into the metabolism of CS by the human gut microbiota, which has promising implications for the development of medical and nutritional therapies for osteoarthritis. Video Abstract.
Topics: Humans; Chondroitin Sulfates; Gastrointestinal Microbiome; Oligosaccharides; Osteoarthritis; Bacteroides
PubMed: 38419055
DOI: 10.1186/s40168-024-01768-2 -
European Journal of Biochemistry May 2001Two novel acharan sulfate lyases (ASL1 and ASL2: no EC number) have been purified from Bacteroides stercoris HJ-15 which was isolated from human intestinal bacteria with...
Two novel acharan sulfate lyases (ASL1 and ASL2: no EC number) have been purified from Bacteroides stercoris HJ-15 which was isolated from human intestinal bacteria with glycosaminoglycan (GAG) degrading enzymes. These enzymes were purified to apparent homogeneity by a combination of QAE-cellulose, DEAE-cellulose, carboxymethyl-Sephadex C-50, hydroxyapatite and HiTrap SP Sephadex C-25 column chromatography with the final specific activity of 50.5 and 76.7 micromol.min-1.mg-1, respectively. Both acharan sulfate lyases are single subunits of 83 kDa by SDS/PAGE and gel filtration. ASL1 showed optimal activity at pH 7.2 and 45 degrees C. ASL1 activity was inhibited by Cu2+, Ni2+ and Co2+, but ASL2 activity was inhibited by Cu2+, Ni2+and Pb2. Both enzymes were slightly inhibited by some agents that modify histidine and cysteine residues, but activated by reducing agents such as DL-dithiothreitol and 2-mercaptoethanol. Both purified bacteroidal acharan sulfate lyases acted to the greatest extent on acharan sulfate, and to a lesser extents on heparan sulfate and heparin. They did not act on de-O-sulfated acharan sulfate. These findings suggest that the biochemical properties of these purified acharan sulfate lyases are different from those of the previously purified heparin lyases, but these enzymes belong to heparinase II.
Topics: Amino Acid Sequence; Bacteroides; Glycosaminoglycans; Heparin Lyase; Humans; Kinetics; Substrate Specificity
PubMed: 11322884
DOI: 10.1046/j.1432-1327.2001.02156.x -
Molecular Medicine (Cambridge, Mass.) May 2021To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact...
OBJECTIVE
To evaluate the taxonomic composition of the gut microbiome in gout patients with and without tophi formation, and predict bacterial functions that might have an impact on urate metabolism.
METHODS
Hypervariable V3-V4 regions of the bacterial 16S rRNA gene from fecal samples of gout patients with and without tophi (n = 33 and n = 25, respectively) were sequenced and compared to fecal samples from 53 healthy controls. We explored predictive functional profiles using bioinformatics in order to identify differences in taxonomy and metabolic pathways.
RESULTS
We identified a microbiome characterized by the lowest richness and a higher abundance of Phascolarctobacterium, Bacteroides, Akkermansia, and Ruminococcus_gnavus_group genera in patients with gout without tophi when compared to controls. The Proteobacteria phylum and the Escherichia-Shigella genus were more abundant in patients with tophaceous gout than in controls. Fold change analysis detected nine genera enriched in healthy controls compared to gout groups (Bifidobacterium, Butyricicoccus, Oscillobacter, Ruminococcaceae_UCG_010, Lachnospiraceae_ND2007_group, Haemophilus, Ruminococcus_1, Clostridium_sensu_stricto_1, and Ruminococcaceae_UGC_013). We found that the core microbiota of both gout groups shared Bacteroides caccae, Bacteroides stercoris ATCC 43183, and Bacteroides coprocola DSM 17136. These bacteria might perform functions linked to one-carbon metabolism, nucleotide binding, amino acid biosynthesis, and purine biosynthesis. Finally, we observed differences in key bacterial enzymes involved in urate synthesis, degradation, and elimination.
CONCLUSION
Our findings revealed that taxonomic variations in the gut microbiome of gout patients with and without tophi might have a functional impact on urate metabolism.
Topics: Biodiversity; Computational Biology; Dysbiosis; Gastrointestinal Microbiome; Gout; Humans; Metagenome; Metagenomics; Protein Interaction Mapping; Protein Interaction Maps; Uric Acid
PubMed: 34030623
DOI: 10.1186/s10020-021-00311-5 -
Gut Feb 2021Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in... (Observational Study)
Observational Study
OBJECTIVE
Although severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was detected in faeces of patients with COVID-19, the activity and infectivity of the virus in the GI tract during disease course is largely unknown. We investigated temporal transcriptional activity of SARS-CoV-2 and its association with longitudinal faecal microbiome alterations in patients with COVID-19.
DESIGN
We performed RNA shotgun metagenomics sequencing on serial faecal viral extractions from 15 hospitalised patients with COVID-19. Sequencing coverage of the SARS-CoV-2 genome was quantified. We assessed faecal microbiome composition and microbiome functionality in association with signatures of faecal SARS-CoV-2 infectivity.
RESULTS
Seven (46.7%) of 15 patients with COVID-19 had stool positivity for SARS-CoV-2 by viral RNA metagenomic sequencing. Even in the absence of GI manifestations, all seven patients showed strikingly higher coverage (p=0.0261) and density (p=0.0094) of the 3' vs 5' end of SARS-CoV-2 genome in their faecal viral metagenome profile. Faecal viral metagenome of three patients continued to display active viral infection signature (higher 3' vs 5' end coverage) up to 6 days after clearance of SARS-CoV-2 from respiratory samples. Faecal samples with signature of high SARS-CoV-2 infectivity had higher abundances of bacterial species , , , , and higher functional capacity for nucleotide de novo biosynthesis, amino acid biosynthesis and glycolysis, whereas faecal samples with signature of low-to-none SARS-CoV-2 infectivity had higher abundances of short-chain fatty acid producing bacteria, , , and .
CONCLUSION
This pilot study provides evidence for active and prolonged 'quiescent' GI infection even in the absence of GI manifestations and after recovery from respiratory infection of SARS-CoV-2. Gut microbiota of patients with active SARS-CoV-2 GI infection was characterised by enrichment of opportunistic pathogens, loss of salutary bacteria and increased functional capacity for nucleotide and amino acid biosynthesis and carbohydrate metabolism.
Topics: Adult; Aged; COVID-19; Feces; Female; Gastrointestinal Microbiome; Hospitalization; Humans; Longitudinal Studies; Male; Middle Aged; Pilot Projects; Prospective Studies; SARS-CoV-2; Young Adult
PubMed: 32690600
DOI: 10.1136/gutjnl-2020-322294