scholarly journals Individual and Group Response of Treatment with Ivacaftor on Airway and Gut Microbiota in People with CF and a S1251N Mutation

2021 ◽  
Vol 11 (5) ◽  
pp. 350
Author(s):  
Maartje I. Kristensen ◽  
Karin M. de Winter-de Groot ◽  
Gitte Berkers ◽  
Mei Ling J. N. Chu ◽  
Kayleigh Arp ◽  
...  

Ivacaftor has been shown to restore the functionality of the S1251N (also known as c.3752G>A) mutated CFTR, which may cause alterations in both airway and gut physiology and micro-environment, resulting in a change of microbiota in these organs. The aim of the present study was to analyze the effects of ivacaftor on the microbial community composition of both airway and gut in subjects with CF carrying one S1251N mutation, using a 16S rRNA gene-based sequencing approach. In 16 subjects with CF, repetitive samples from airways and gut were collected just before, and 2 months after, and, for 8 patients, also 9 and 12 months after, start of ivacaftor. 16S rRNA based sequencing identified 344 operational taxonomical units (OTUs) in a total of 139 samples (35 nasopharyngeal, 39 oropharyngeal, 29 sputum, and 36 fecal samples). Ivacaftor significantly enhanced bacterial diversity and overall microbiota composition in the gut (p < 0.01). There were no significant changes in the overall microbial composition and alpha diversity in upper and lower airways of these patients after ivacaftor treatment. Treatment with ivacaftor induces changes in gut microbiota whereas airway microbiota do not change significantly over time.

2019 ◽  
Vol 97 (Supplement_3) ◽  
pp. 293-294
Author(s):  
Camila S Marcolla ◽  
Benjamin Willing

Abstract This study aimed to characterize poultry microbiota composition in commercial farms using 16S rRNA sequencing. Animals raised in sanitized environments have lower survival rates when facing pathogenic challenges compared to animals naturally exposed to commensal organisms. We hypothesized that intensive rearing practices inadvertently impair chicken exposure to microbes and the establishment of a balanced gut microbiota. We compared gut microbiota composition of broilers (n = 78) and layers (n = 20) from different systems, including commercial intensive farms with and without in-feed antibiotics, organic free-range farms, backyard-raised chickens and chickens in an experimental farm. Microbial community composition of conventionally raised broilers was significantly different from antibiotic-free broilers (P = 0.012), from broilers raised outdoors (P = 0.048) and in an experimental farm (P = 0.006) (Fig1). Significant community composition differences were observed between antibiotic-fed and antibiotic-free chickens (Fig2). Antibiotic-free chickens presented higher alpha-diversity, higher relative abundance of Deferribacteres, Fusobacteria, Bacteroidetes and Actinobacteria, and lower relative abundance of Firmicutes, Clostridiales and Enterobacteriales than antibiotic-fed chickens (P &lt; 0.001) (Fig3). Microbial community composition significantly changed as birds aged. In experimental farm, microbial community composition was significant different for 7, 21 and 35 day old broilers (P &lt; 0.001), and alpha diversity increased from 7 to 21d (P &lt; 0.024), but not from 21 to 35d; whereas, in organic systems, increases in alpha-diversity were observed from 7d to 21d, and from 21d to 35d (P &lt; 0.05). Broilers and layers raised together showed no differences in microbiota composition and alpha diversity (P &gt; 0.8). It is concluded that production practices consistently impact microbial composition, and that antibiotics significantly reduces microbial diversity. We are now exploring the impact of differential colonization in a controlled setting, to determine the impact of the microbes associated with extensively raised chickens. This study will support future research and the development of methods to isolate and introduce beneficial microbes to commercial systems.


2021 ◽  
Vol 9 (2) ◽  
pp. 278
Author(s):  
Shen Jean Lim ◽  
Miriam Aguilar-Lopez ◽  
Christine Wetzel ◽  
Samia V. O. Dutra ◽  
Vanessa Bray ◽  
...  

The preterm infant gut microbiota is influenced by environmental, endogenous, maternal, and genetic factors. Although siblings share similar gut microbial composition, it is not known how genetic relatedness affects alpha diversity and specific taxa abundances in preterm infants. We analyzed the 16S rRNA gene content of stool samples, ≤ and >3 weeks postnatal age, and clinical data from preterm multiplets and singletons at two Neonatal Intensive Care Units (NICUs), Tampa General Hospital (TGH; FL, USA) and Carle Hospital (IL, USA). Weeks on bovine milk-based fortifier (BMF) and weight gain velocity were significant predictors of alpha diversity. Alpha diversity between siblings were significantly correlated, particularly at ≤3 weeks postnatal age and in the TGH NICU, after controlling for clinical factors. Siblings shared higher gut microbial composition similarity compared to unrelated individuals. After residualizing against clinical covariates, 30 common operational taxonomic units were correlated between siblings across time points. These belonged to the bacterial classes Actinobacteria, Bacilli, Bacteroidia, Clostridia, Erysipelotrichia, and Negativicutes. Besides the influence of BMF and weight variables on the gut microbial diversity, our study identified gut microbial similarities between siblings that suggest genetic or shared maternal and environmental effects on the preterm infant gut microbiota.


Author(s):  
Xun Kang ◽  
Yanhong Wang ◽  
Siping Li ◽  
Xiaomei Sun ◽  
Xiangyang Lu ◽  
...  

The midgut microbial community composition, structure, and function of field-collected mosquitoes may provide a way to exploit microbial function for mosquito-borne disease control. However, it is unclear how adult mosquitoes acquire their microbiome, how the microbiome affects life history traits and how the microbiome influences community structure. We analyzed the composition of 501 midgut bacterial communities from field-collected adult female mosquitoes, including Aedes albopictus, Aedes galloisi, Culex pallidothorax, Culex pipiens, Culex gelidus, and Armigeres subalbatus, across eight habitats using the HiSeq 4000 system and the V3−V4 hyper-variable region of 16S rRNA gene. After quality filtering and rarefaction, a total of 1421 operational taxonomic units, belonging to 29 phyla, 44 families, and 43 genera were identified. Proteobacteria (75.67%) were the most common phylum, followed by Firmicutes (10.38%), Bacteroidetes (6.87%), Thermi (4.60%), and Actinobacteria (1.58%). The genera Rickettsiaceae (33.00%), Enterobacteriaceae (20.27%), Enterococcaceae (7.49%), Aeromonadaceae (7.00%), Thermaceae (4.52%), and Moraxellaceae (4.31%) were dominant in the samples analyzed and accounted for 76.59% of the total genera. We characterized the midgut bacterial communities of six mosquito species in Hainan province, China. The gut bacterial communities were different in composition and abundance, among locations, for all mosquito species. There were significant differences in the gut microbial composition between some species and substantial variation in the gut microbiota between individuals of the same mosquito species. There was a marked variation in different mosquito gut microbiota within the same location. These results might be useful in the identification of microbial communities that could be exploited for disease control.


2019 ◽  
Vol 8 (1) ◽  
pp. 60
Author(s):  
Mohd Baasir Gaisawat ◽  
Chad W. MacPherson ◽  
Julien Tremblay ◽  
Amanda Piano ◽  
Michèle M. Iskandar ◽  
...  

Clostridium (C.) difficile-infection (CDI), a nosocomial gastrointestinal disorder, is of growing concern due to its rapid rise in recent years. Antibiotic therapy of CDI is associated with disrupted metabolic function and altered gut microbiota. The use of probiotics as an adjunct is being studied extensively due to their potential to modulate metabolic functions and the gut microbiota. In the present study, we assessed the ability of several single strain probiotics and a probiotic mixture to change the metabolic functions of normal and C. difficile-infected fecal samples. The production of short-chain fatty acids (SCFAs), hydrogen sulfide (H2S), and ammonia was measured, and changes in microbial composition were assessed by 16S rRNA gene amplicon sequencing. The C. difficile-infection in fecal samples resulted in a significant decrease (p < 0.05) in SCFA and H2S production, with a lower microbial alpha diversity. All probiotic treatments were associated with significantly increased (p < 0.05) levels of SCFAs and restored H2S levels. Probiotics showed no effect on microbial composition of either normal or C. difficile-infected fecal samples. These findings indicate that probiotics may be useful to improve the metabolic dysregulation associated with C. difficile infection.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Mei Wang ◽  
Brooke Smith ◽  
Brock Adams ◽  
Miller Tran ◽  
Ryan Dilger ◽  
...  

Abstract Objectives Enterotoxigenic Escherichia coli (ETEC) are an important cause of diarrhea in human infants and young farm animals. Osteopontin (OPN), a glycoprotein present in high concentration in human milk, has immunomodulatory functions, which could indirectly impact the microbiota. Furthermore, a previous study has shown fecal microbiota composition differs between wild-type and OPN knockout mice. Herein, the effects of OPN-enriched algae on the gut microbiota composition and volatile fatty acid (VFA) concentrations of ETEC-infected piglets were assessed. Methods Naturally-farrowed piglets were sow-reared for 21 days and then randomized to two weaning diets: WT (formula + 1% wild-type algae) or OPN (formula + 1% OPN-enriched algae). On postnatal day (PND) 31, all piglets were infected orally with a live culture of ETEC (1010 colony-forming unit/3 mL dose) daily for three consecutive days. On PND 41, ascending colon (AC) contents were collected. Gut microbiota was assessed by sequencing V3-V4 regions of 16S rRNA gene and VFAs were determined by gas chromatography. Alpha-diversity and VFAs were analyzed using PROC MIXED procedure of SAS. Beta-diversity was evaluated by permutational multivariate analysis of variance (PERMANOVA) and differential abundance analysis on the bacterial genera was performed using DESeq2 package of R. Results Shannon indices were lower in the AC contents of OPN piglets compared to WT piglets. The overall colonic microbiota of OPN piglets differed from that of WT piglets (PERMANOVA P = 0.015). At genus level, OPN-enriched algae increased the abundance of Streptococcus, decreased the abundances of Sutterella, Candidatus Soleaferrea, dga-11 gut group, Rikenellaceae RC9 gut group, Ruminococcaceae UCG-010, unculturedRuminococcaceae, Prevotella 2 and 7 compared to piglets consuming wild-type algae (P < 0. 05). OPN piglets also had higher (P < 0.05) concentrations of acetate, propionate, butyrate and valerate compared to WT. Conclusions In ETEC infected piglets, 1% OPN-enriched algae decreased alpha-diversity and modulated the microbiota composition and VFA profiles compared to 1% WT algae. Other studies have shown that OPN inhibits biofilm formation in vitro, but future research is needed to assess in vivo microbiome-modulation mechanisms. Funding Sources Triton Algae Innovations.


2020 ◽  
Author(s):  
Dandan Jiang ◽  
Xin He ◽  
Marc Valitutto ◽  
Li Chen ◽  
Qin Xu ◽  
...  

Abstract Background:The Chinese monal (Lophophorus lhuysii) is an endangered bird species, with a wild population restricted to the mountains of southwest China, and only one known captive population in the world. We investigated the fecal microbiota and metabolome of wild and captive Chinese monals to explore differences and similarities in nutritional status and digestive characteristics. An integrated approach combining 16S ribosomal RNA (16S rRNA) gene sequencing and ultra-high performance liquid chromatography (UHPLC) based metabolomics were used to examine the fecal microbiota composition and the metabolomic profile of Chinese monals. Results: The results showed that the alpha diversity of gut microbes in the wild group were significantly higher than that in the captive group and the core bacterial taxa in the two groups showed remarkable differences at phylum, class, order, and family levels. Metabolomic profiling also revealed differences, mainly related to galactose, starch and sucrose metabolism, fatty acid, bile acid biosynthesis and bile secretion. Furthermore, strong correlations of metabolite types and bacterial genus were detected. Conclusions: There were remarkable differences in the gut microbiota composition and metabolomic profile between wild and captive Chinese monals. This study has established a baseline for a normal gut microbiota and metabolomic profile for wild Chinese monals, thus allowing us to evaluate if differences seen in captive organisms have an impact on their overall health and reproduction.


Author(s):  
Caspar Bundgaard-Nielsen ◽  
Nadia Ammitzbøll ◽  
Yusuf Abdi Isse ◽  
Abdisalam Muqtar ◽  
Ann-Maria Jensen ◽  
...  

AbstractBackgroundNew sensitive techniques have revealed a large population of bacteria in the human urinary tract, challenging the perception of the urine of healthy humans being sterile. While the role of this urinary microbiota is unknown, dysbiosis has been linked to disorders like urgency urinary incontinence and interstitial cystitis. When comparing studies it is crucial to account for possible confounders introduced due to methodological differences. Here we investigated whether storage condition or time of collection, had any impact on the urinary microbial composition.ResultsFor comparison of different storage conditions, urine was collected from five healthy adult female donors, and analyzed by 16S rRNA gene sequencing. Using the same methods, the daily or day-to-day variation in urinary microbiota was investigated in nineteen healthy donors, including four women, five men, five girls, and five boys. With the exception of two male adult donors, none of the tested conditions gave rise to significant differences in alpha and beta diversities between individuals. Conclusion: The composition of the urinary microbiota was found to be highly resilient to changes introduced by storage temperature and duration. In addition, we did not observe any intrapersonal daily or day-to-day variations in microbiota composition in women, girls or boys.Together our study supports flexibility in study design, when conducting urinary microbiota studies.Author summaryThe discovery of bacteria native to the urinary tract in healthy people, a location previously believed to be sterile, has prompted research into the clinical potential of these bacteria. However, methodological weaknesses can significantly influence such studies, and thus development of robust techniques for investigating these bacteria are needed. In the present study, we investigated whether differences in storage following collection, could affect the bacterial composition of urine samples. Next, we investigated if this composition exhibited daily or day-to-day variations.Firstly, we found, that the bacterial composition of urine could be maintained by storage at −80 °C, −20 °C, or refrigerated at 4 °C. Secondly, the bacterial composition of urine remained stable over time. Overall, the results of this study provide information important to study design in future investigations into the clinical implications of urinary bacteria.


2021 ◽  
Author(s):  
Artur Trzebny ◽  
Anna Slodkowicz-Kowalska ◽  
Johanna Björkroth ◽  
Miroslawa Dabert

AbstractThe animal gut microbiota consist of many different microorganisms, mainly bacteria, but archaea, fungi, protozoans, and viruses may also be present. This complex and dynamic community of microorganisms may change during parasitic infection. In the present study, we investigated the effect of the presence of microsporidians on the composition of the mosquito gut microbiota and linked some microbiome taxa and functionalities to infections caused by these parasites. We characterised bacterial communities of 188 mosquito females, of which 108 were positive for microsporidian DNA. To assess how bacterial communities change during microsporidian infection, microbiome structures were identified using 16S rRNA microbial profiling. In total, we identified 46 families and four higher taxa, of which Comamonadaceae, Enterobacteriaceae, Flavobacteriaceae and Pseudomonadaceae were the most abundant mosquito-associated bacterial families. Our data suggest that the mosquito gut microbial composition varies among host species. In addition, we found a correlation between the microbiome composition and the presence of microsporidians. The prediction of metagenome functional content from the 16S rRNA gene sequencing suggests that microsporidian infection is characterised by some bacterial species capable of specific metabolic functions, especially the biosynthesis of ansamycins and vancomycin antibiotics and the pentose phosphate pathway. Moreover, we detected a positive correlation between the presence of microsporidian DNA and bacteria belonging to Spiroplasmataceae and Leuconostocaceae, each represented by a single species, Spiroplasma sp. PL03 and Weissella cf. viridescens, respectively. Additionally, W. cf. viridescens was observed only in microsporidian-infected mosquitoes. More extensive research, including intensive and varied host sampling, as well as determination of metabolic activities based on quantitative methods, should be carried out to confirm our results.


2020 ◽  
Vol 8 (8) ◽  
pp. 1151
Author(s):  
Peris M. Munyaka ◽  
Fany Blanc ◽  
Jordi Estellé ◽  
Gaëtan Lemonnier ◽  
Jean-Jacques Leplat ◽  
...  

The gut microbiota comprises a large and diverse community of bacteria that play a significant role in swine health. Indeed, there is a tight association between the enteric immune system and the overall composition and richness of the microbiota, which is key in the induction, training and function of the host immunity, and may therefore, influence the immune response to vaccination. Using vaccination against Mycoplasma hyopneumoniae (M. hyo) as a model, we investigated the potential of early-life gut microbiota in predicting vaccine response and explored the post-vaccination dynamics of fecal microbiota at later time points. At 28 days of age (0 days post-vaccination; dpv), healthy piglets were vaccinated, and a booster vaccine was administered at 21 dpv. Blood samples were collected at 0, 21, 28, 35, and 118 dpv to measure M. hyo-specific IgG levels. Fecal samples for 16S rRNA gene amplicon sequencing were collected at 0, 21, 35, and 118 dpv. The results showed variability in antibody response among individual pigs, whilst pre-vaccination operational taxonomic units (OTUs) primarily belonging to Prevotella, [Prevotella], Anaerovibrio, and Sutterella appeared to best-predict vaccine response. Microbiota composition did not differ between the vaccinated and non-vaccinated pigs at post-vaccination time points, but the time effect was significant irrespective of the animals’ vaccination status. Our study provides insight into the role of pre-vaccination gut microbiota composition in vaccine response and emphasizes the importance of studies on full metagenomes and microbial metabolites aimed at deciphering the role of specific bacteria and bacterial genes in the modulation of vaccine response.


2021 ◽  
Author(s):  
Jialiang Li ◽  
Xueyan Li ◽  
Sina Zhang ◽  
Chen Jin ◽  
Zixia Lin ◽  
...  

Abstract BACKGROUNDThe liver-microbiome axis is implicated in the pathogenesis of hepatobiliary cancer, and the role of the gut microbiota in cholangiocarcinoma (CCA) remains unclear.METHODWe conducted a case-control study on the intestinal flora of 33 CCA patients and 47 cholelithiasis individuals. We performed 16S rRNA gene sequencing to identify disease-related gut microbiota and assess the potential of the intestinal microbiome as a non-invasive biomarker for CCA.RESULTWe found that gut microbiome of CCA patients had a significantly higher alpha diversity (Shannon and Observed species indices, p = 0.006 and p = 0.02, respectively) and an overall different microbial community composition (p = 0.032). The genus Muribaculaceae_unclassified was most strongly associated with CCA (p < 0.001). We put forward a disease predictive model including twelve intestinal microbiome genera distinguished CCA patients from CF patients with an area under curve (AUC) of approximately 0.93 (95%CI, 0.85–0.987). The forecasting performance of this model was better than CA19-9. Moreover, genera Ezakiella and Garciella were only observed among intrahepatic cholangiocarcinoma patients. Further, we assessed predicted functional modules alternations CCA patients and uncovered a microbiota pattern specific to CCA.CONCLUSIONOur findings provide evidence of the intestinal microbiome as a non-invasive biomarker for CCA.


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