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Frontiers in Microbiology 2022β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active...
β-glucuronidases (GUS) of intestinal bacteria remove glucuronic acid from glucoronides, reversing phase II metabolism of the liver and affecting the level of active deconjugated metabolites deriving from drugs or xenobiotics. Two hundred seventy-nine non-redundant GUS sequences are known in the gut microbiota, classified in seven structural categories (NL, L1, L2, mL1, mL2, mL1,2, and NC) with different biocatalytic properties. In the present study, the intestinal metagenome of 60 healthy subjects from five geographically different cohorts was assembled, binned, and mined to determine qualitative and quantitative differences in GUS profile, potentially affecting response to drugs and xenobiotics. Each metagenome harbored 4-70 different GUS, altogether accounting for 218. The amount of intestinal bacteria with at least one GUS gene was highly variable, from 0.7 to 82.2%, 25.7% on average. No significant difference among cohorts could be identified, except for the Ethiopia (ETH) cohort where GUS-encoding bacteria were significantly less abundant. The structural categories were differently distributed among the metagenomes, but without any statistical significance related to the cohorts. GUS profiles were generally dominated by the category NL, followed by mL1, L2, and L1. The GUS categories most involved in the hydrolysis of small molecules, including drugs, are L1 and mL1. Bacteria contributing to these categories belonged to , , , , , , , and . Bacteria harboring L1 GUS were generally scarcely abundant (<1.3%), except in three metagenomes, where they reached up to 24.3% for the contribution of and Bacteria harboring mL1 GUS were significantly more abundant (mean = 4.6%), with representing a major contributor. Albeit mL1 enzymes are less active than L1 ones, likely plays a pivotal role in the deglucuronidation, due to its remarkable abundance in the microbiomes. The observed broad interindividual heterogeneity of GUS profiles, particularly of the L1 and mL1 categories, likely represent a major driver of pharmacomicrobiomics variability, affecting drug response and toxicity. Different geographical origins, genetic, nutritional, and lifestyle features of the hosts seemed not to be relevant in the definition of glucuronidase activity, albeit they influenced the richness of the GUS profile.
PubMed: 35308380
DOI: 10.3389/fmicb.2022.826994 -
Cancers Apr 2024The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies...
The combination of atezolizumab and bevacizumab has become the first-line treatment for patients with unresectable hepatocellular carcinoma (HCC). However, no studies have reported on specific intestinal microbiota associated with the efficacy of atezolizumab and bevacizumab. In this study, we analyzed fecal samples collected before treatment to investigate the relationship between the intestinal microbiome and the efficacy of atezolizumab and bevacizumab. A total of 37 patients with advanced HCC who were treated with atezolizumab and bevacizumab were enrolled. Fecal samples were collected from the patients, and they were divided into responder ( = 28) and non-responder ( = 9) groups. We compared the intestinal microbiota of the two groups and analyzed the intestinal bacteria associated with prognosis using QIIME2. The alpha and beta diversities were not significantly different between both groups, and the proportion of microbiota was similar. The relative abundance of and was higher in the responder group than in the non-responder group. When the prognosis was analyzed by the presence or absence of those bacteria, patients without both had a significantly poorer prognosis. Differences in intestinal microbiome are involved in the therapeutic effect of atezolizumab and bevacizumab.
PubMed: 38730627
DOI: 10.3390/cancers16091675 -
Microbiology Spectrum Aug 2022Clostridioides difficile infection (CDI) is associated with high mortality rates among patients with chronic illnesses. We aimed to identify avoidable risk factors to...
Clostridioides difficile infection (CDI) is associated with high mortality rates among patients with chronic illnesses. We aimed to identify avoidable risk factors to reduce the mortality rate in CDI patients. A total of 306 patients with diarrhea and clinical suspicion of CDI were enrolled, and fecal samples were gathered from 145 patients. CDI was diagnosed by fecal positivity for the C. difficile gene. Risk factors associated with death within 180 days were identified using Cox regression analysis. The fecal microbiota was determined through bacterial 16S rRNA gene sequencing. Of the patients with diarrhea, 240 (mean age, 69.1 years) were positive for CDI, and 91 died within 180 days. Multivariate analysis revealed that male sex, high Charlson Comorbidity Index and McCabe scores, high serum C-reactive protein levels, low hematocrit levels, low absolute eosinophil counts, high neutrophil/lymphocyte ratios, and daily use of proton pump inhibitors (PPIs) were independent risk factors for overall mortality. Cumulative analyses confirmed the association of duration-dependent PPI use with a high mortality rate. Fecal microbiota analyses showed associations of decreased relative abundance of Ruminococcus gnavus ( = 0.001) and Prevotella copri ( = 0.025) and increased relative abundance of Parabacteroides merdae ( = 0.001) and Clostridioides difficile ( = 0.040) with higher mortality rates in patients with CDI. Moreover, these microbiota changes were correlated with the duration of PPI use. This article demonstrates that daily PPI use was the only avoidable risk factor for death. With more extended PPI use, the mortality rate was higher in patients with CDI. Decreases in Prevotella copri and Ruminococcus gnavus and increases in Parabacteroides merdae and Clostridioides difficile in line with daily PPI use duration were significantly associated with the death of CDI patients. Our findings provide in-depth insights into the cautious use of PPIs in chronically ill patients with CDI.
Topics: Aged; Bacterial Toxins; Bacteroidetes; Clostridiales; Clostridioides difficile; Clostridium Infections; Diarrhea; Dysbiosis; Humans; Male; Prevotella; Proton Pump Inhibitors; RNA, Ribosomal, 16S
PubMed: 35863023
DOI: 10.1128/spectrum.00486-22 -
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 -
Gut Microbes 2021The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut...
The gut microbiota in the hepatitis B virus related acute-on-chronic liver failure (HBV-ACLF) is poorly defined. We aim to uncover the characteristics of the gut microbiota in HBV-ACLF and in other HBV associated pathologies. We analyzed the gut microbiome in patients with HBV-ACLF or other HBV associated pathologies and healthy individuals by 16S rRNA sequencing and metagenomic sequencing of fecal samples. 212 patients with HBV-ACLF, 252 with chronic hepatitis B (CHB), 162 with HBV-associated cirrhosis (HBV-LC) and 877 healthy individuals were recruited for the study. CHB and HBV-LC patients are grouped as HBV-Other. We discovered striking differences in the microbiome diversity between the HBV-ACLF, HBV-Other and healthy groups using 16S rRNA sequencing. The ratio of cocci to bacilli was significantly elevated in the HBV-ACLF group compared with healthy group. Further analysis within the HBV-ACLF group identified 52 genera showing distinct richness within the group where was enriched in the progression group whilst was enriched in the regression group. Metagenomic sequencing validated these findings and further uncovered an enrichment of in progression group, while and dominated the regression group. Importantly, our analysis revealed that there was a rapid increase of during the progression of HBV-ACLF. The gut microbiota displayed distinct composition at different phases of HBV-ACLF. High abundance of is associated with progression while that of is associated with regression of HBV-ACLF. Therefore, the microbiota features hold promising potential as prognostic markers for HBV-ACLF.
Topics: Acute-On-Chronic Liver Failure; Adult; Bacteria; Disease Progression; Feces; Female; Gastrointestinal Microbiome; Hepatitis B virus; Hepatitis B, Chronic; Humans; Male; Metagenomics; Middle Aged
PubMed: 34006193
DOI: 10.1080/19490976.2021.1921925 -
Frontiers in Nutrition 2023The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
UNLABELLED
The aim of the study was to evaluate the effects of Active or Sedentary lifestyle on saliva microbiota composition in Italian schoolchildren.
METHODS
Male (114) and female children (8-10 years) belonging to five primary schools in the neighborhoods of Turin were classified as active (A) or sedentary (S) based on PAQ-C-It questionnaire. PCR amplification of salivary DNA targeted the hypervariable V3-V4 regions of the 16S rRNA bacterial genes. DADA2 workflow was used to infer the Amplicon Sequence Variants and the taxonomic assignments; the beta-diversity was obtained by PCoA with the UniFrac method; LEfSe algorithm, threshold at 5%, and Log LDA cutoff at ±0.5 were used to identify differently abundant species in A compared to S saliva sample. Daily food intake was assessed by 3-Days food record. The metabolic potential of microbial communities was assessed by PICRUSt.
RESULTS
No significant differences were found in individual's gender distribution ( = 0.411), anthropometry, BMI ( > 0.05), and all diet composition between A and S groups ( > 0.05). Eight species were differently abundant: (LDA score = -3.76; FDR = 1.5×10-03), (LDA score = -3.17; FDR = 7.45×10-03), (LDA score = -2.96; FDR = 2.76×10-05), (LDA score = -2.43; FDR = 1.3×10-02) are enriched in the A group; , (LDA score = -3.9; FDR = 5.27×10-04), (LDA score = 4.23; FDR = 1.93×10-02), (LDA score = 4.43; FDR = 1.31×10-02; LDA score = 2.94; FDR = 7.45×10-03) are enriched in the S group. A prevalence of superpathway of fatty acid biosynthesis initiation () and catechol degradation II (meta-cleavage pathway) was found in saliva from A compared to S children.
CONCLUSION
Our results showed that active children had an enrichment of species and genera mainly associated with a healthier profile. By contrast, the genera and the species enriched in the sedentary group could be linked to human diseases.
PubMed: 37671197
DOI: 10.3389/fnut.2023.1226891 -
Anaerobe Jun 2010Using 16S rRNA sequence analysis, we report the first isolation of Parabacteroides goldsteinii as a monobacterial isolate from blood culture in a patient with abdominal...
Using 16S rRNA sequence analysis, we report the first isolation of Parabacteroides goldsteinii as a monobacterial isolate from blood culture in a patient with abdominal sepsis. P. goldsteinii phenotypically resembles Parabacteroides merdae and Parabacteroides distasonis and may be misidentified by commonly used enzymatic systems, suggesting that it may be more frequently present in clinical specimens than previously appreciated but either misidentified or ignored.
Topics: Abdominal Abscess; Aged, 80 and over; Bacteremia; Bacteroidetes; Female; Humans; Virulence
PubMed: 20139022
DOI: 10.1016/j.anaerobe.2010.01.001 -
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 -
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 -
Gut Microbes 2022Fecal microbiota transplantation (FMT) is currently used for treating infection and explored for other clinical applications in experimental trials. However, the... (Clinical Trial)
Clinical Trial
Fecal microbiota transplantation (FMT) is currently used for treating infection and explored for other clinical applications in experimental trials. However, the effectiveness of this therapy could vary, and partly depend on the donor's bacterial species engraftment, whose evaluation is challenging because there are no cost-effective strategies for accurately tracking the microbe transference. In this regard, the precise identification of bacterial species inhabiting the human gut is essential to define their role in human health unambiguously. We used Nanopore-based device to sequence bacterial operons (16S-ITS-23S) and to reveal species-level abundance changes in the human gut microbiota of a FMT trial. By assessing the donor and recipient microbiota before and after FMT, we further evaluated whether this molecular approach reveals strain-level genetic variation to demonstrate microbe transfer and engraftment. Strict control over sequencing data quality and major microbiota covariates was critical for accurately estimating the changes in gut microbial species abundance in the recipients after FMT. We detected strain-level variation via single-nucleotide variants (SNVs) at regions in a species-specific manner. We showed that it was possible to explore successfully the donor-bacterial strain (e.g., engraftment in recipients of the FMT by assessing the nucleotide frequencies at rrn-associated SNVs. Our findings indicate that the engraftment of donors' microbiota is to some extent correlated with the improvement of metabolic health in recipients and that parameters such as the baseline gut microbiota configuration, sex, and age of donors should be considered to ensure the success of FMT in humans. The study was prospectively registered at the Dutch Trial registry - NTR4488 (https://www.trialregister.nl/trial/4488).
Topics: Bacteria; Fecal Microbiota Transplantation; Feces; Gastrointestinal Microbiome; Humans; Metabolic Syndrome; Nucleotides
PubMed: 35604764
DOI: 10.1080/19490976.2022.2078621