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 ◽  
...  

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.

2018 ◽  
Author(s):  
Charles Burdet ◽  
Sakina Sayah-Jeanne ◽  
Thu Thuy Nguyen ◽  
Perrine Hugon ◽  
Frédérique Sablier-Gallis ◽  
...  

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.


2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S382-S382
Author(s):  
Charles Burdet ◽  
Thu Thuy Nguyen ◽  
Nathalie Saint-Lu ◽  
Sakina Sayah-Jeanne ◽  
Perrine Hugon ◽  
...  

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


2019 ◽  
Vol 63 (10) ◽  
Author(s):  
Charles Burdet ◽  
Thu Thuy Nguyen ◽  
Xavier Duval ◽  
Stéphanie Ferreira ◽  
Antoine Andremont ◽  
...  

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.


2013 ◽  
Vol 79 (24) ◽  
pp. 7827-7836 ◽  
Author(s):  
Danilo Ercolini ◽  
Erica Pontonio ◽  
Francesca De Filippis ◽  
Fabio Minervini ◽  
Antonietta La Storia ◽  
...  

ABSTRACTThe bacterial ecology during rye and wheat sourdough preparation was described by 16S rRNA gene pyrosequencing. Viable plate counts of presumptive lactic acid bacteria, the ratio between lactic acid bacteria and yeasts, the rate of acidification, a permutation analysis based on biochemical and microbial features, the number of operational taxonomic units (OTUs), and diversity indices all together demonstrated the maturity of the sourdoughs during 5 to 7 days of propagation. Flours were mainly contaminated by metabolically active genera (Acinetobacter,Pantoea,Pseudomonas,Comamonas,Enterobacter,Erwinia, andSphingomonas) belonging to the phylumProteobacteriaorBacteroidetes(genusChryseobacterium). Their relative abundances varied with the flour. Soon after 1 day of propagation, this population was almost completely inhibited except for theEnterobacteriaceae. Although members of the phylumFirmicuteswere present at very low or intermediate relative abundances in the flours, they became dominant soon after 1 day of propagation. Lactic acid bacteria were almost exclusively representative of theFirmicutesby this time.Weissellaspp. were already dominant in rye flour and stably persisted, though they were later flanked by theLactobacillus sakeigroup. There was a succession of species during 10 days of propagation of wheat sourdoughs. The fluctuation between dominating and subdominating populations ofL. sakeigroup,Leuconostocspp.,Weissellaspp., andLactococcus lactiswas demonstrated. Other subdominant species such asLactobacillus plantarumwere detectable throughout propagation. As shown by PCR-denaturing gradient gel electrophoresis (PCR-DGGE) analysis,Saccharomyces cerevisiaedominated throughout the sourdough propagation. Notwithstanding variations due to environmental and technology determinants, the results of this study represent a clear example of how the microbial ecology evolves during sourdough preparation.


2015 ◽  
Vol 81 (9) ◽  
pp. 3192-3204 ◽  
Author(s):  
Carlo Giuseppe Rizzello ◽  
Ivana Cavoski ◽  
Jelena Turk ◽  
Danilo Ercolini ◽  
Luana Nionelli ◽  
...  

ABSTRACTTriticum turgidumsubsp.durumwas grown according to four farming systems: conventional (CONV), organic with cow manure (OMAN) or green manure (OLEG), and without inputs (NOINPUT). Some chemical and technological characteristics differed between CONVand organic flours. As shown by two-dimensional electrophoresis (2-DE) analysis, OMANand OLEGflours showed the highest number of gliadins, and OMANflour also had the highest number of high-molecular-mass glutenins. Type I sourdoughs were prepared at the laboratory level through a back-slopping procedure, and the bacterial ecology during sourdough preparation was described by 16S rRNA gene pyrosequencing. Before fermentation, the dough made with CONVflour showed the highest bacterial diversity. Flours were variously contaminated by genera belonging to theProteobacteria,Firmicutes, andActinobacteria. Mature sourdoughs were completely and stably dominated by lactic acid bacteria. The diversity ofFirmicuteswas the highest for mature sourdoughs made with organic and, especially, NOINPUTflours. Beta diversity analysis based on the weighted UniFrac distance showed differences between doughs and sourdoughs. Those made with CONVflour were separated from the other with organic flours. Lactic acid bacterium microbiota structure was qualitatively confirmed through the culturing method. As shown by PCR-denaturing gradient gel electrophoresis (DGGE) analysis, yeasts belonging to the generaSaccharomyces,Candida,Kazachstania, andRhodotorulaoccurred in all sourdoughs. Levels of bound phenolic acids and phytase and antioxidant activities differed depending on the farming system. Mature sourdoughs were used for bread making. Technological characteristics were superior in the breads made with organic sourdoughs. The farming system is another determinant affecting the sourdough microbiota. The organic cultivation of durum wheat was reflected along the flour-sourdough fermentation-bread axis.


2011 ◽  
Vol 80 (1) ◽  
pp. 62-73 ◽  
Author(s):  
Charlie G. Buffie ◽  
Irene Jarchum ◽  
Michele Equinda ◽  
Lauren Lipuma ◽  
Asia Gobourne ◽  
...  

ABSTRACTAntibiotic-induced changes in the intestinal microbiota predispose mammalian hosts to infection with antibiotic-resistant pathogens.Clostridium difficileis a Gram-positive intestinal pathogen that causes colitis and diarrhea in patients following antibiotic treatment. Clindamycin predisposes patients toC. difficilecolitis. Here, we have used Roche-454 16S rRNA gene pyrosequencing to longitudinally characterize the intestinal microbiota of mice following clindamycin treatment in the presence or absence ofC. difficileinfection. We show that a single dose of clindamycin markedly reduces the diversity of the intestinal microbiota for at least 28 days, with an enduring loss of ca. 90% of normal microbial taxa from the cecum. Loss of microbial complexity results in dramatic sequential expansion and contraction of a subset of bacterial taxa that are minor contributors to the microbial consortium prior to antibiotic treatment. Inoculation of clindamycin-treated mice withC. difficile(VPI 10463) spores results in rapid development of diarrhea and colitis, with a 4- to 5-day period of profound weight loss and an associated 40 to 50% mortality rate. Recovering mice resolve diarrhea and regain weight but remain highly infected with toxin-producing vegetativeC. difficilebacteria and, in comparison to the acute stage of infection, have persistent, albeit ameliorated cecal and colonic inflammation. The microbiota of “recovered” mice remains highly restricted, and mice remain susceptible toC. difficileinfection at least 10 days following clindamycin, suggesting that resolution of diarrhea and weight gain may result from the activation of mucosal immune defenses.


2014 ◽  
Vol 80 (8) ◽  
pp. 2546-2554 ◽  
Author(s):  
Zongxin Ling ◽  
Zailing Li ◽  
Xia Liu ◽  
Yiwen Cheng ◽  
Yueqiu Luo ◽  
...  

ABSTRACTIncreasing evidence suggests that perturbations in the intestinal microbiota composition of infants are implicated in the pathogenesis of food allergy (FA), while the actual structure and composition of the intestinal microbiota in human beings with FA remain unclear. Microbial diversity and composition were analyzed with parallel barcoded 454 pyrosequencing targeting the 16S rRNA gene hypervariable V1-V3 regions in the feces of 34 infants with FA (17 IgE mediated and 17 non-IgE mediated) and 45 healthy controls. Here, we showed that several key FA-associated bacterial phylotypes, but not the overall microbiota diversity, significantly changed in infancy fecal microbiota with FA and were associated with the development of FA. The proportion of abundantBacteroidetes,Proteobacteria, andActinobacteriaphyla were significantly reduced, while theFirmicutesphylum was highly enriched in the FA group (P< 0.05). AbundantClostridiaceae1 organisms were prevalent in infants with FA at the family level (P= 0.016). FA-enriched phylotypes negatively correlated with interleukin-10, for example, the generaEnterococcusandStaphylococcus. Despite profound interindividual variability, levels of 20 predominant genera were significantly different between the FA and healthy control groups (P< 0.05). Infants with IgE-mediated FA had increased levels ofClostridium sensu strictoandAnaerobacterand decreased levels ofBacteroidesandClostridiumXVIII (P< 0.05). A positive correlation was observed betweenClostridium sensu strictoand serum-specific IgE (R= 0.655,P< 0.001). The specific microbiota signature could distinguish infants with IgE-mediated FA from non-IgE-mediated ones. Detailed microbiota analysis of a well-characterized cohort of infants with FA showed that dysbiosis of fecal microbiota with several FA-associated key phylotypes may play a pathogenic role in FA.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e8168
Author(s):  
Diana H. Taft ◽  
Samir Akre ◽  
Nicolas Madrid ◽  
Andre Knoesen ◽  
David A. Mills ◽  
...  

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.


2018 ◽  
Vol 84 (24) ◽  
Author(s):  
Matthew E. Mokszycki ◽  
Mary Leatham-Jensen ◽  
Jon L. Steffensen ◽  
Ying Zhang ◽  
Karen A. Krogfelt ◽  
...  

ABSTRACTA novelin vitrogut model was developed to better understand the interactions betweenEscherichia coliand the mouse cecal mucus commensal microbiota. The gut model is simple and inexpensive while providing an environment that largely replicates the nonadherent mucus layer of the mouse cecum. 16S rRNA gene profiling of the cecal microbial communities of streptomycin-treated mice colonized withE. coliMG1655 orE. coliNissle 1917 and the gut model confirmed that the gut model properly reflected the community structure of the mouse intestine. Furthermore, the results from thein vitrogut model mimic the results of publishedin vivocompetitive colonization experiments. The gut model is initiated by the colonization of streptomycin-treated mice, and then the community is serially transferred in microcentrifuge tubes in an anaerobic environment generated in anaerobe jars. The nutritional makeup of the cecum is simulated in the gut model by using a medium consisting of porcine mucin, mouse cecal mucus, HEPES-Hanks buffer (pH 7.2), Cleland’s reagent, and agarose. Agarose was found to be essential for maintaining the stability of the microbial community in the gut model. The outcome of competitions betweenE. colistrains in thein vitrogut model is readily explained by the “restaurant hypothesis” of intestinal colonization. This simple model system potentially can be used to more fully understand how different members of the microbiota interact physically and metabolically during the colonization of the intestinal mucus layer.IMPORTANCEBoth commensal and pathogenic strains ofEscherichia coliappear to colonize the mammalian intestine by interacting physically and metabolically with other members of the microbiota in the mucus layer that overlays the cecal and colonic epithelium. However, the use of animal models and the complexity of the mammalian gut make it difficult to isolate experimental variables that might dictate the interactions betweenE. coliand other members of the microbiota, such as those that are critical for successful colonization. Here, we describe a simple and relatively inexpensivein vitrogut model that largely mimicsin vivoconditions and therefore can facilitate the manipulation of experimental variables for studying the interactions ofE. coliwith the intestinal microbiota.


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

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


Sign in / Sign up

Export Citation Format

Share Document