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Journal of Clinical Medicine Apr 2021Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity...
Fecal microbiota transplantation following triple-antibiotic therapy (amoxicillin/fosfomycin/metronidazole) improves dysbiosis caused by reduced Bacteroidetes diversity in patients with ulcerative colitis (UC). We investigated the correlation between Bacteroidetes species abundance and UC activity. Fecal samples from 34 healthy controls and 52 patients with active UC (Lichtiger's clinical activity index ≥5 or Mayo endoscopic subscore ≥1) were subjected to next-generation sequencing with as a target in bacterial metagenome analysis. A multiplex gene expression assay using colonoscopy-harvested mucosal tissues determined the involvement of Bacteroidetes species in the mucosal immune response. In patients with UC, six Bacteroides species exhibited significantly lower relative abundance, and twelve Bacteroidetes species were found significantly correlated with at least one metric of disease activity. The abundance of five Bacteroidetes species (, , , , and ) was correlated with three metrics, and their cumulative relative abundance was strongly correlated with the sum of Mayo endoscopic subscore (R = -0.71, = 2 × 10). Five genes (, , , , and ) associated with UC pathogenesis were expressed by the 12 key species. The loss of key species may exacerbate UC activity, serving as potential biomarkers.
PubMed: 33920646
DOI: 10.3390/jcm10081749 -
Theranostics 2021Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in...
Multi-omics study reveals that statin therapy is associated with restoration of gut microbiota homeostasis and improvement in outcomes in patients with acute coronary syndrome.
Prior chronic treatment with statins has been shown to be associated with more favorable outcomes in patients with acute coronary syndrome (ACS). Specific changes in the gut microbiota and microbial metabolites have been shown to influence the progression of coronary artery disease. However, the critical microbial and metabolomic changes associated with the cardiovascular protective effects of statins in ACS remain elusive. In the present study, we performed 16S rRNA sequencing and serum metabolomic analysis in 36 ACS patients who had received chronic statin treatment, 67 ACS patients who had not, and 30 healthy volunteers. A follow-up study was conducted. Metagenomic functional prediction of important bacterial taxa was achieved using PICRUSt2. : Statins modulated the gut microbiome of ACS patients towards a healthier status, i.e., reducing potentially pathogenic bacteria such as but increasing beneficial bacteria such as , and . Moreover, prior chronic statin therapy was associated with improved outcome in ACS patients. Multi-omics analysis revealed that specific changes in bacterial taxa were associated with disease severity or outcomes either directly or by mediating metabolites such as fatty acids and prenol lipids. Finally, we discovered that important taxa associated with statins were correlated with fatty acid- and isoprenoid-related pathways that were predicted by PICRUSt2. Our study suggests that statin treatment might benefit ACS patients by modulating the composition and function of the gut microbiome, which might result in improved circulating metabolites and reduced metabolic risk. Our findings provide new insights for understanding the heterogenic roles of statins in ACS patients through host gut microbiota metabolic interactions.
Topics: Acute Coronary Syndrome; Bacteria; Female; Follow-Up Studies; Gastrointestinal Microbiome; Healthy Volunteers; Homeostasis; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Metabolomics; Middle Aged; RNA, Ribosomal, 16S
PubMed: 33897881
DOI: 10.7150/thno.55946 -
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 -
Fertility and Sterility Jun 2020To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes.
OBJECTIVE
To identify different microbial species in women with polycystic ovary syndrome (PCOS) and reveal a possible relationship between gut dysbiosis and pathological changes.
DESIGN
Cross-sectional study.
SETTING
Academic institution.
PATIENT(S)
Reproductive-aged women with PCOS (n = 14) and controls (n = 14) from the Centre for Reproductive Medicine.
INTERVENTION(S)
Shotgun metagenomic sequencing on fecal samples from patients, and clinical parameters (including body mass index, endocrine hormone levels, and glycemia level) gathered for correlation analysis.
MAIN OUTCOME MEASURE(S)
Identification of different gut microbial strains and relativity between microbiota and clinical parameters.
RESULT(S)
We found several microbial strains were statistically significantly more abundant in the PCOS group, including Parabacteroides merdae, Bacteroides fragilis, and strains of Escherichia and Shigella, whereas Faecalibacterium prausnitzii was enriched in the control group. Metagenomic species (MGS) analysis revealed that the microbes of the PCOS group were negatively correlated with those of the control group. Of note, we observed a positive correlation between MGS relevant to PCOS and endocrine disorders, including body mass index and elevated levels of serum testosterone, luteinizing hormone, and antimüllerian hormone. Functional alterations, reflected by Kyoto Encyclopedia of Genes and Genomes orthologues, could imply potential mechanisms of microbial involvement in the developmental progress of PCOS.
CONCLUSION(S)
Our findings suggest an intimate association and potential mechanisms linking microbial dysbiosis and the pathophysiologic changes of PCOS. We address the importance of monitoring and modulating microbial composition and functional shifts in future clinical practice.
Topics: Adult; Bacteria; Case-Control Studies; Cross-Sectional Studies; Dysbiosis; Feces; Female; Gastrointestinal Microbiome; Humans; Intestines; Metagenomics; Polycystic Ovary Syndrome; Young Adult
PubMed: 32482258
DOI: 10.1016/j.fertnstert.2020.01.027 -
New Microbes and New Infections Nov 2019sp. nov., strain Marseille-P2231 (= CSURP2231 = DSM 101860) is a new species within the family . It was isolated from a stool specimen of a 25-year-old healthy woman....
sp. nov., strain Marseille-P2231 (= CSURP2231 = DSM 101860) is a new species within the family . It was isolated from a stool specimen of a 25-year-old healthy woman. Its genome was 5 013 798 bp long with a 45.7 mol% G+C content. The closest species based on 16S rRNA sequence was strain JCM 9497 with 98.19% sequence similarity. Considering phenotypic features and comparative genome studies, we proposed the strain Marseille-P2231 as the type strain of sp. nov., a new species within the genus
PubMed: 31641517
DOI: 10.1016/j.nmni.2019.100602 -
PloS One 2019Gut microbiota is closely related to age. Studies from Europe and the U.S. identified featured microbiota in different age groups for the elderly. Asian studies mainly...
BACKGROUND
Gut microbiota is closely related to age. Studies from Europe and the U.S. identified featured microbiota in different age groups for the elderly. Asian studies mainly focused on people living in longevity areas. Featured microbiota for the elderly people of different age groups, especially in the centenarian in the general population, has not been well investigated in China.
METHOD
We conducted a comparative study by including 198 subjects of three age groups (65-70, 90-99, and 100+ years) in East China. Information regarding age, sex, height, weight, waist circumference, hip circumference, food preference, smoking status and alcohol consumption were collected by using a structured questionnaire. Fecal samples for each participant were collected as well. 16S rRNA gene sequencing were employed to analyze the gut microbiota composition. Logistic regression with LASSO feature selection was used to identify featured taxa in different age groups and to assess their potential interactions with other factors such as lifestyle.
RESULT
The gut microbiota of the 90-99 year and 100+ year age groups showed more diversity, robustness, and richness compared with the 65-70 year age group. PCoA analysis showed a clear separation between the 65-70 and 100+ year age groups. At the species level, Bacteroides fragilis, Parabacteroides merdae, Ruminococcus gnavus, Coprococcus and Clostridium perfringens increased, but Bacteroides vulgatus, Ruminococcus sp.5139BFAA and Clostridium sp.AT5 decreased in the 90-99 year age group. The age differences in gut microbiota were similar across the strata of smoking, alcohol consumption status and food preference.
CONCLUSION
Our study demonstrated age differences in many aspects of gut microbiota, such as overall diversity, microbiota structure, and relative abundance of key taxa. Moreover, the gut microbiota of centenarian was significantly different from those of younger age groups of the elderly.
Topics: Aged; Aged, 80 and over; Bacteria; China; Europe; Feces; Female; Gastrointestinal Microbiome; Humans; Longevity; Male; RNA, Ribosomal, 16S
PubMed: 31639130
DOI: 10.1371/journal.pone.0222763 -
AMB Express May 2019Although fecal microbiota transplantation (FMT) has become a research hotspot, studies on comparison of the active fecal bacteria suspension under different preparation...
Although fecal microbiota transplantation (FMT) has become a research hotspot, studies on comparison of the active fecal bacteria suspension under different preparation conditions are limited. This study investigated the abundances of active bacterial community in pig FMT suspension that produced under different oxygen concentrations or cryopreservation conditions. Fecal samples from a Landrace × Yorkshire sow were used to prepare fecal bacteria suspension under the anaerobic (AN group) and aerobic conditions (AE group), respectively. And then half of the anaerobic fecal bacteria suspension was cryopreservation in - 80 °C (AN-CR group) for 1 week. The microbial RNA in the fecal bacteria suspension was extracted before and after cryopreservation, and reverse transcribed into cDNA. MiSeq sequencing 16S rRNA gene of bacterial cDNA showed that the bacterial diversity in the AN group was significantly higher than that in the AE group. Comparing with the sows' fecal sample, the relative abundances of Lactobacillus johnsonii, Lactobacillus coleohominis and Parabacteroides merdae in AN, AE and AN-CR groups were reduced. The short-term cryopreservation had low impact on the structure of the active bacterial community in the fecal bacterial suspension. These results suggest that fecal bacteria suspension can be better prepared under strict anaerobic condition, and that fecal bacteria suspension can be cryopreserved in - 80 °C for a short time.
PubMed: 31076926
DOI: 10.1186/s13568-019-0787-4 -
JFMS Open Reports 2019A 13-year-old spayed female domestic shorthair cat presented with pleural effusion and suspected triaditis. Intake vitals and leukocytosis were consistent with a...
CASE SUMMARY
A 13-year-old spayed female domestic shorthair cat presented with pleural effusion and suspected triaditis. Intake vitals and leukocytosis were consistent with a diagnosis of systemic inflammatory response syndrome. Biochemical analysis confirmed a pleural fluid-to-serum bile ratio consistent with a diagnosis of biliothorax. Abdominal ultrasound failed to identify a definitive gall bladder but noted a hypoechoic tubular structure ventral to the liver and contacting the diaphragm. Thoracic ultrasound identified a hyperechoic structure contacting the diaphragm at the same location. Thoracoabdominal CT scan identified a fluid-dense tubular structure extending from ventral to the liver, through a diaphragmatic defect and directly communicating with the pleural space, suspected to be an abnormal gall bladder. The cat was humanely euthanized, and post-mortem analysis confirmed a cholecystopleural fistula arising from the gall bladder with multifocal abscesses, mixed inflammatory hepatic infiltrates and small-cell gastrointestinal lymphoma. Culture of the abscess isolated , meeting the reported feline criteria for sepsis.
RELEVANCE AND NOVEL INFORMATION
To our knowledge, spontaneous cholecystopleural fistula formation leading to biliothorax and sepsis has not been previously reported in the cat. This case highlights a novel sequela of gall bladder disease in this species, and biliothorax should be a differential diagnosis for pleural effusion in cats with evidence of cholecystitis or triaditis.
PubMed: 30792876
DOI: 10.1177/2055116919830206 -
Protein Science : a Publication of the... Dec 2018β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and...
β-Glucuronidase (GUS) enzymes in the gastrointestinal tract are involved in maintaining mammalian-microbial symbiosis and can play key roles in drug efficacy and toxicity. Parabacteroides merdae GUS was identified as an abundant mini-Loop 2 (mL2) type GUS enzyme in the Human Microbiome Project gut metagenomic database. Here, we report the crystal structure of P. merdae GUS and highlight the differences between this enzyme and extant structures of gut microbial GUS proteins. We find that P. merdae GUS exhibits a distinct tetrameric quaternary structure and that the mL2 motif traces a unique path within the active site, which also includes two arginines distinctive to this GUS. We observe two states of the P. merdae GUS active site; a loop repositions itself by more than 50 Å to place a functionally-relevant residue into the enzyme's catalytic site. Finally, we find that P. merdae GUS is able to bind to homo and heteropolymers of the polysaccharide alginic acid. Together, these data broaden our understanding of the structural and functional diversity in the GUS family of enzymes present in the human gut microbiome and point to specialization as an important feature of microbial GUS orthologs.
Topics: Bacteroidaceae; Catalytic Domain; Crystallography, X-Ray; Gastrointestinal Microbiome; Glucuronidase; Humans; Models, Molecular; Protein Conformation
PubMed: 30230652
DOI: 10.1002/pro.3507 -
Cell Host & Microbe Jul 2018Why ketogenic diet (KD) effectively controls seizures in some people with epilepsy is unclear. In a recent issue of Cell, Olson et al. (2018) showed that KD prevents...
Why ketogenic diet (KD) effectively controls seizures in some people with epilepsy is unclear. In a recent issue of Cell, Olson et al. (2018) showed that KD prevents seizures by upregulating key bacterial species (Akkermansia muciniphila and Parabacteroides merdae). These bacteria synergize to decrease gammaglutamylation of amino acids, increase hippocampal GABA/Glutamate ratios, and, ultimately, prevent seizures.
PubMed: 30001522
DOI: 10.1016/j.chom.2018.06.014