scholarly journals Antibiotic-induced dysbiosis predicts mortality in an animal model ofClostridium difficileinfection

2018 ◽  
Author(s):  
Charles Burdet ◽  
Sakina Sayah-Jeanne ◽  
Thu Thuy Nguyen ◽  
Perrine Hugon ◽  
Frédérique Sablier-Gallis ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Diversity Index ◽  
Diversity Indices ◽  
Shannon Index ◽  
Gene Profiling ◽  
Rrna Gene ◽  
Toxigenic Strain ◽  
Unifrac Distance ◽  
Unweighted Unifrac ◽  
The Relationship

AbstractBackgroundAntibiotic disruption of the intestinal microbiota favors colonization byClostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis, and quantified the link between this intensity and mortality.MethodsWe administered either moxifloxacin (n=70) or clindamycin (n=60) to hamsters by subcutaneous injection from day 1 (D1) to D5, and challenged them with aC. difficiletoxigenic strain at D3. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0and D3using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time ofC. difficilechallenge and studied their capacity to predict subsequent death of the animals.ResultsIncreasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (p<10−5for the change of Shannon index in moxifloxacin-treated animals and p<10−9in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the ROC curve of 0.89 [95%CI, 0.82;0.95] and 0.95 [0.90;0.98], respectively.ConclusionsAltogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency to the DAV131A dose; mortality afterC. difficilechallenge was related to the intensity of dysbiosis in a similar manner with the two antibiotics.

scholarly journals Antibiotic-Induced Dysbiosis Predicts Mortality in an Animal Model ofClostridium difficileInfection

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
Charles Burdet ◽  
Sakina Sayah-Jeanne ◽  
Thu Thuy Nguyen ◽  
Perrine Hugon ◽  
Frédérique Sablier-Gallis ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Diversity Index ◽  
Diversity Indices ◽  
Shannon Index ◽  
Gene Profiling ◽  
Receiver Operating Curve ◽  
Rrna Gene ◽  
Unifrac Distance ◽  
Content Type ◽  
The Relationship

ABSTRACTAntibiotic disruption of the intestinal microbiota favors colonization byClostridium difficile. Using a charcoal-based adsorbent to decrease intestinal antibiotic concentrations, we studied the relationship between antibiotic concentrations in feces and the intensity of dysbiosis and quantified the link between this intensity and mortality. We administered either moxifloxacin (n= 70) or clindamycin (n= 60) to hamsters by subcutaneous injection from day 1 (D1) to D5and challenged them with aC. difficiletoxigenic strain at D3. Hamsters received various doses of a charcoal-based adsorbent, DAV131A, to modulate intestinal antibiotic concentrations. Gut dysbiosis was evaluated at D0and D3using diversity indices determined from 16S rRNA gene profiling. Survival was monitored until D16. We analyzed the relationship between fecal antibiotic concentrations and dysbiosis at the time ofC. difficilechallenge and studied their capacity to predict subsequent death of the animals. Increasing doses of DAV131A reduced fecal concentrations of both antibiotics, lowered dysbiosis, and increased survival from 0% to 100%. Mortality was related to the level of dysbiosis (P< 10−5for the change of Shannon index in moxifloxacin-treated animals andP< 10−9in clindamycin-treated animals). The Shannon diversity index and unweighted UniFrac distance best predicted death, with areas under the receiver operating curve (ROC) of 0.89 (95% confidence interval [CI], 0.82, 0.95) and 0.95 (0.90, 0.98), respectively. Altogether, moxifloxacin and clindamycin disrupted the diversity of the intestinal microbiota with a dependency on the DAV131A dose; mortality afterC. difficilechallenge was related to the intensity of dysbiosis in similar manners with the two antibiotics.

scholarly journals Change in Bacterial Diversity of Fecal Microbiota Drives Mortality in a Hamster Model of Antibiotic-induced Clostridium difficile Colitis

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S382-S382
Author(s):  
Charles Burdet ◽  
Thu Thuy Nguyen ◽  
Nathalie Saint-Lu ◽  
Sakina Sayah-Jeanne ◽  
Perrine Hugon ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Diversity Indices ◽  
Fecal Microbiota ◽  
Gene Profiling ◽  
Rrna Gene ◽  
Hamster Model ◽  
Unweighted Unifrac ◽  
Curtis Dissimilarity ◽  
Oral Adsorbent ◽  
Induced Changes

Abstract Background C. difficile (C diff) infection results from antibiotic-induced changes in colonic microbiota. DAV131A, an oral adsorbent-based product, can sequester antibiotic (AB) residues in the gut and reduce mortality in a hamster model of moxifloxacin (MXF) or clindamycin (CM) induced C diffcolitis. We studied the link between changes of the bacterial diversity within the fecal microbiota and mortality in this model. Methods Male Syrian hamsters were administered 30 mg/kg MXF or 5 mg/kg CM subcutaneously once a day for 5 days (D1 to D5) and orally infected at D3 with 104C diffspores. They were orally administered various doses of DAV131A (0, and 200 to 900 mg/kg twice a day), from D1 to D8. Survival was monitored up to D16 and feces were collected (D1 and D3) to characterize the microbiota by 16S rRNA gene profiling. Changes of various α- (Shannon, Observed OTUs and Chao1) and β- (Bray-Curtis dissimilarity and [un]weighted UniFrac) diversity indices between D1 and D3 were obtained for each animal. We analyzed links between (i) DAV131A dose and changes of bacterial diversity and (ii) changes of bacterial diversity and mortality using non parametric tests and logistic regression. Results Data from 70 and 60 animals were available in the MXF and CM studies, among which 10 and 28 died, respectively. Increasing doses of DAV131A reduced mortality from 100% to 0% and reduced changes in bacterial diversity of the fecal microbiota. Very strong predictors of mortality were changes in Shannon and unweighted UniFrac indices, which were markedly less affected in hamsters who survived (see table below median (min; max) according to vital status and area under the ROC curve, AUROC). Conclusion The extent of AB-induced changes in gut bacterial diversity correlated with increased mortality in a hamster model of C diff colitis. Higher doses of DAV131A protected fecal microbiota disruption and hence mortality. Disclosures C. Burdet, Da Volterra: Consultant and Research Contractor, Consulting fee; N. Saint-Lu, Da Volterra: Employee, Salary; S. Sayah-Jeanne, Da Volterra: Employee, Salary; P. Hugon, Da Volterra: Employee, Salary; F. Sablier-Gallis, Da Volterra: Employee, Salary; S. Ferreira, Genoscreen: Employee, Salary; A. Andremont, Da Volterra: Consultant, Consulting fee; F. Mentré, Da Volterra: Consultant and Research Contractor, Consulting fee; J. De Gunzburg, Da Volterra: Consultant and Shareholder, Consulting fee

scholarly journals Comprehensive Analysis of Risk Factors for Periodontitis Focusing on the Saliva Microbiome and Polymorphism

2021 ◽  
Vol 18 (12) ◽  
pp. 6430
Author(s):  
Naoki Toyama ◽  
Daisuke Ekuni ◽  
Daisuke Matsui ◽  
Teruhide Koyama ◽  
Masahiro Nakatochi ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Alpha Diversity ◽  
Study Data ◽  
Shannon Index ◽  
Rrna Gene ◽  
Nucleotide Polymorphisms ◽  
Unifrac Distance ◽  
Microbiome Composition ◽  
Significant Difference ◽  
Unweighted Unifrac

Few studies have exhaustively assessed relationships among polymorphisms, the microbiome, and periodontitis. The objective of the present study was to assess associations simultaneously among polymorphisms, the microbiome, and periodontitis. We used propensity score matching with a 1:1 ratio to select subjects, and then 22 individuals (mean age ± standard deviation, 60.7 ± 9.9 years) were analyzed. After saliva collection, V3-4 regions of the 16S rRNA gene were sequenced to investigate microbiome composition, alpha diversity (Shannon index, Simpson index, Chao1, and abundance-based coverage estimator) and beta diversity using principal coordinate analysis (PCoA) based on weighted and unweighted UniFrac distances. A total of 51 single-nucleotide polymorphisms (SNPs) related to periodontitis were identified. The frequencies of SNPs were collected from Genome-Wide Association Study data. The PCoA of unweighted UniFrac distance showed a significant difference between periodontitis and control groups (p < 0.05). There were no significant differences in alpha diversity and PCoA of weighted UniFrac distance (p > 0.05). Two families (Lactobacillaceae and Desulfobulbaceae) and one species (Porphyromonas gingivalis) were observed only in the periodontitis group. No SNPs showed significant expression. These results suggest that periodontitis was related to the presence of P. gingivalis and the families Lactobacillaceae and Desulfobulbaceae but not SNPs.

scholarly journals Environmental Temperatures Affect the Gastrointestinal Microbes of the Chinese Giant Salamander

2021 ◽  
Vol 12 ◽  
Author(s):  
Lifeng Zhu ◽  
Wei Zhu ◽  
Tian Zhao ◽  
Hua Chen ◽  
Chunlin Zhao ◽  
...  
Keyword(s):  
Potential Effect ◽  
Shannon Index ◽  
Effect Of Temperature ◽  
Sample Type ◽  
Gastrointestinal Microbiome ◽  
Unifrac Distance ◽  
Alpha And Beta Diversity ◽  
Significant Difference ◽  
Unweighted Unifrac ◽  
Sample Time

An increasing number of studies have shown that warming also influences the animal gut microbiome (altering the community structure and decreasing its diversity), which might further impact host fitness. Here, based on an analysis of the stomach and gut (the entire intestine: from the anterior intestine to the cloaca) microbiome in laboratory larva of giant salamanders (Andrias davidianus) under different living water temperatures (5, 15, and 25°C) at two sample time points (80 and 330 days after the acclimation), we investigated the potential effect of temperature on the gastrointestinal microbiome community. We found the significant Interaction between sampling time and temperature, or type (stomach and gut) on Shannon index in the gastrointestinal microbiome of the giant salamanders. We also found the significant difference in Shannon index among temperature groups within the same sample type (stomach or gut) at each sample time. 10% of variation in microbiome community could be explained by temperature alone in the total samples. Both the stomach and gut microbiomes displayed the highest similarity in the microbiome community (significantly lowest pairwise unweighted Unifrac distance) in the 25-degree group between the two sampling times compared to those in the 5-degree and 15-degree groups. Moreover, the salamanders in the 25°C treatment showed the highest food intake and body mess compared to that of other temperature treatments. A significant increase in the abundance of Firmicutes in the gastrointestinal microbiome on day 330 with increasing temperatures might be caused by increased host metabolism and food consumption. Therefore, we speculate that the high environmental temperature might indirectly affect both alpha and beta diversity of the gastrointestinal microbiome.

scholarly journals Impact of Antibiotic Gut Exposure on the Temporal Changes in Microbiome Diversity

2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Charles Burdet ◽  
Thu Thuy Nguyen ◽  
Xavier Duval ◽  
Stéphanie Ferreira ◽  
Antoine Andremont ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Day Treatment ◽  
Temporal Changes ◽  
Shannon Index ◽  
Gene Profiling ◽  
Intestinal Microbiome ◽  
Rrna Gene ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Mixed Effect

ABSTRACT Although the global deleterious impact of antibiotics on the intestinal microbiota is well known, temporal changes in microbial diversity during and after an antibiotic treatment are still poorly characterized. We used plasma and fecal samples collected frequently during treatment and up to one month after from 22 healthy volunteers assigned to a 5-day treatment by moxifloxacin (n = 14) or no intervention (n = 8). Moxifloxacin concentrations were measured in both plasma and feces, and bacterial diversity was determined in feces by 16S rRNA gene profiling and quantified using the Shannon index and number of operational taxonomic units (OTUs). Nonlinear mixed effect models were used to relate drug pharmacokinetics and bacterial diversity over time. Moxifloxacin reduced bacterial diversity in a concentration-dependent manner, with a median maximal loss of 27.5% of the Shannon index (minimum [min], 17.5; maximum [max], 27.7) and 47.4% of the number of OTUs (min, 30.4; max, 48.3). As a consequence of both the long fecal half-life of moxifloxacin and the susceptibility of the gut microbiota to moxifloxacin, bacterial diversity indices did not return to their pretreatment levels until days 16 and 21, respectively. Finally, the model characterized the effect of moxifloxacin on bacterial diversity biomarkers and provides a novel framework for analyzing antibiotic effects on the intestinal microbiome.

scholarly journals Resident microbes of lactation rooms and daycares

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8168
Author(s):  
Diana H. Taft ◽  
Samir Akre ◽  
Nicolas Madrid ◽  
Andre Knoesen ◽  
David A. Mills ◽  
...  
Keyword(s):  
Beta Diversity ◽  
Alpha Diversity ◽  
Illumina Miseq ◽  
Shannon Index ◽  
Rrna Gene ◽  
Sample Collection ◽  
Unifrac Distance ◽  
Modern Development ◽  
Temperature And Humidity ◽  
The Impact

Dedicated lactation rooms are a modern development as mothers return to work while still providing breastmilk to their absent infants. This study describes the built environment microbiome of lactation rooms and daycares, and explores the influence of temperature and humidity on the microbiome of lactation rooms. Sterile swabs were used to collect samples from five different sites in lactation rooms at University of California, Davis and from five different sites in daycares located in Davis, California. DNA from the swabs was extracted and the V4 region of the 16S rRNA gene was sequenced using Illumina MiSeq. Temperature and relative humidity data were collected on a subset of the lactation rooms. Sampled lactation rooms could be either dedicated lactation rooms or could also serve other functions (e.g., combined lactation room and restroom lounge). The majority of sequence reads were identified as belonging to family Moraxellaceae, with 73% of all reads included in analysis identified as an unknown species of Acinetobacter. Alpha diversity was analyzed using the Shannon index, while beta diversity was analyzed using unweighted and weighted UniFrac distance. The Jaccard distance was used to measure amount of change at sampling locations between time points for analysis of the impact of temperature and humidity on the microbiome. There were significant differences in the beta diversity of the microbiome of lactation rooms by room type. There were also significant differences in the beta diversity of the microbiome by sample collection location. There were no significant differences in either alpha or beta diversity associated with room temperature or humidity. Additional studies are needed to understand if the differences in lactation room type may result in differences in the breastmilk microbiome of milk collected in those rooms, and to what extent any such differences may influence the infant microbiome.

scholarly journals Systematic Bias Introduced by Genomic DNA Template Dilution in 16S rRNA Gene-Targeted Microbiota Profiling in Human Stool Homogenates

mSphere ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Francesco Multinu ◽  
Sean C. Harrington ◽  
Jun Chen ◽  
Patricio R. Jeraldo ◽  
Stephen Johnson ◽  
...  
Keyword(s):  
16S Rrna ◽  
16S Rrna Gene ◽  
Genomic Dna ◽  
Rrna Gene ◽  
Microbial Composition ◽  
Unifrac Distance ◽  
Β Diversity ◽  
Unweighted Unifrac ◽  
Stool Samples ◽  
Community Representation

ABSTRACT Variability in representation of microbial communities can be caused by differences in microbial composition or artifacts introduced at sample collection or processing. Alterations in community representation introduced by variations in starting DNA concentrations have not been systematically investigated in stool samples. The goal of this study was to evaluate the effect of the genomic DNA (gDNA) concentration in the resulting 16S rRNA gene library composition and compare its effect to other sample processing variables in homogenized human fecal material. Compared to a gDNA input of 1 ng/μl, inputs of ≤1.6 × 10 −3  ng/μl resulted in a marked decrease in the concentration of the 16S rRNA gene amplicon ( P < 0.001). Low gDNA concentrations (≤1.6 × 10 −3  ng/μl) were also associated with a decrease ( P < 0.001) in the number of operational taxonomic units and significant divergence in β-diversity profiles (unweighted UniFrac distance, P < 0.001), as characterized by an overestimation of Proteobacteria and underestimation of Firmicutes . Even a gDNA concentration of 4 × 10 −2  ng/μl showed a significant impact on the β-diversity profile (unweighted UniFrac distance, P = 0.03). Overall, the gDNA concentration explained 22.4% to 38.1% of the microbiota variation based on various β-diversity measures ( P < 0.001). By comparison, the DNA extraction methods and PCR volumes tested did not significantly affect the microbial composition profile, and the PCR cycling method explained less than 3.7% of the microbiota variation (weighted UniFrac distance, P = 0.03). The 16S rRNA gene yield and the microbial community representation of human homogenized stool samples are significantly altered by gDNA template concentrations of ≤1.6 × 10 −3  ng/μl. In addition, data from studies with a gDNA input of ≤4 × 10 −2  ng/μl should be interpreted with caution. IMPORTANCE The genomic DNA input for stool samples utilized for microbiome composition has not been determined. In this study, we determined the reliable threshold level under which conclusions drawn from the data may be compromised. We also determined the type of microbial bias introduced by less-than-ideal genomic input.

scholarly journals Species enumeration and diversity of fire experimental plot at Olokemeji Forest Reserve, Ogun State, Nigeria

Agro-Science ◽  
2021 ◽  
Vol 20 (2) ◽  
pp. 37-41
Author(s):  
A.J. Oloketuyi ◽  
O.D. Akinyemi ◽  
D.M. Taiwo ◽  
O.R. Jeminiwa ◽  
A.A. Ayodele
Keyword(s):  
Diversity Index ◽  
Abundant Species ◽  
Diversity Indices ◽  
Shannon Index ◽  
Experimental Plot ◽  
Gmelina Arborea ◽  
Forest Reserve ◽  
Ogun State ◽  
Evenness Index ◽  
High Dominance

The fire experimental plot of a total landed area of 0.174 ha was divided into three equal parts designated Plot A, Plot B and Plot C, corresponding to the early burnt, the late burnt and the control plot, respectively. Out of the 15 species of trees identified, six species belong to Fabaceae- Mimosoideae family and other families represented are Combretaceae, Meliaceae, Lamiaceae, Rubiaceae, Anacardiaceae, Urtiaceae and Sapotaceae. Gmelina arborea was the most abundant species and it was found in plot A, B and C. The diversity indices enumerated were Dominance index, Simpson index, Shannon index or diversity index and evenness index. Plot C had the highest abundance (species count), followed by Plot A and Plot B. While Plot B depicted a high dominance, dominance was low in Plot A and lowest in Plot C. This means that a particular species was dominating Plot B, which was Gmelina arborea. This Gmelina arborea also dominated Plot A but to a lesser extent compared to Plot B. Plot C was richer in species than Plot A and Plot B. The Shannon index was low across the three plots, but considerably highest in Plot C. Evenness index was moderate at Plot C, implying that there was an even distribution of tree species in Plot C, while evenness was low at Plot A and Plot B. Comparing the present data with the older data, it is clear that the fire experimental plot has undergone deforestation over the years, which requires urgent attention and reforestation. Key words: cluster, dendogram, deforestation, burning, richness

scholarly journals Molecular characterization of the intestinal microbiota in patients with and without abdominal bloating

2016 ◽  
Vol 310 (6) ◽  
pp. G417-G426 ◽  
Author(s):  
Tamar Ringel-Kulka ◽  
Andrew K. Benson ◽  
Ian M. Carroll ◽  
Jaehyoung Kim ◽  
Ryan M. Legge ◽  
...  
Keyword(s):  
Intestinal Microbiota ◽  
Operational Taxonomic Unit ◽  
Rrna Gene ◽  
Linear Discriminant ◽  
Abdominal Bloating ◽  
Well Differentiated ◽  
Irritable Bowel ◽  
The Relationship ◽  
The 16S Rrna Gene

Recent studies have demonstrated differences in the intestinal microbiota between patients with irritable bowel syndrome (IBS) and healthy controls (HC), suggesting a role for the intestinal microbiota in the pathogenesis of IBS. Alterations in the microbiota have also been implicated in the pathogenesis of abdominal bloating, a commonly reported symptom in IBS. We investigated the relationship between the intestinal microbiota, abdominal bloating, and altered bowel patterns in a cohort of patients with IBS and HC. The 16S rRNA gene from fresh fecal samples was amplified and pyrosequenced by using Roche-454 Titanium chemistry. A Core Measurable Microbiome (CMM) was generated for Operational Taxonomic Unit (OTU) detected in >75% of all samples and compositional features of CMM were compared between groups by Linear Discriminant Analysis (LDA). IBS differentiated from HC by LDA using continuous variation in the species/OTUs or the CMM genera. When subcategorized based on bloating symptoms and bowel characteristics, the same subjects were also well differentiated from one another and from HC. ANOVA analysis showed quantitative species/OTU differences between the subgroups including IBS with and without bloating, and subtypes based on bowel characteristics. The clear LDA differentiation and the significant microbial taxa differences between the groups imply a significant association of the microbiota with bloating symptoms and bowel characteristics in IBS. These changes in the microbiota may serve as a biomarker for IBS and its clinical subtypes and suggest a role for the intestinal microbiota in the pathogenesis of the main symptoms of the disorder.

scholarly journals Ceftriaxone and Cefotaxime Have Similar Effects on the Intestinal Microbiota in Human Volunteers Treated by Standard-Dose Regimens

2019 ◽  
Vol 63 (6) ◽  
Author(s):  
Charles Burdet ◽  
Nathalie Grall ◽  
Morgane Linard ◽  
Antoine Bridier-Nahmias ◽  
Michèle Benhayoun ◽  
...  
Keyword(s):  
Bacterial Diversity ◽  
Intestinal Microbiota ◽  
Standard Dose ◽  
Generation Cephalosporin ◽  
Gene Profiling ◽  
Pharmacokinetic Analysis ◽  
Rrna Gene ◽  
Open Label ◽  
Gram Negative ◽  
Human Volunteers

ABSTRACT Ceftriaxone has a higher biliary elimination than cefotaxime (40% versus 10%), which may result in a more pronounced impact on the intestinal microbiota. We performed a monocenter, randomized open-label clinical trial in 22 healthy volunteers treated by intravenous ceftriaxone (1 g/24 h) or cefotaxime (1 g/8 h) for 3 days. We collected fecal samples for phenotypic analyses, 16S rRNA gene profiling, and measurement of the antibiotic concentration and compared the groups for the evolution of microbial counts and indices of bacterial diversity over time. Plasma samples were drawn at day 3 for pharmacokinetic analysis. The emergence of 3rd-generation-cephalosporin-resistant Gram-negative enteric bacilli (Enterobacterales), Enterococcus spp., or noncommensal microorganisms was not significantly different between the groups. Both antibiotics reduced the counts of total Gram-negative enteric bacilli and decreased the bacterial diversity, but the differences between the groups were not significant. All but one volunteer from each group exhibited undetectable levels of antibiotic in feces. Plasma pharmacokinetic endpoints were not correlated to alteration of the bacterial diversity of the gut. Both antibiotics markedly impacted the intestinal microbiota, but no significant differences were detected when standard clinical doses were administered for 3 days. This might be related to the similar daily amounts of antibiotics excreted through the bile using a clinical regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT02659033.)

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