scholarly journals Trikafta therapy alters the CF lung mucus metabolome reshaping microbiome niche space

Author(s):  
Lauren Sosinski ◽  
Christian Martin-Hernandez ◽  
Kerri A Neugebauer ◽  
Lydia-Ann J Ghuneim ◽  
Douglas V Guzior ◽  
...  

Novel small molecule therapies for cystic fibrosis (CF) are showing promising efficacy and becoming more widely available since recent FDA approval. The newest of these is a triple therapy of Elexacaftor-Tezacaftor-Ivacaftor (ETI). Little is known about how these drugs will affect polymicrobial lung infections, which are the leading cause of morbidity and mortality among people with CF (pwCF). We analyzed the sputum microbiome and metabolome from pwCF (n=24) before and after TKT therapy using 16S rRNA gene amplicon sequencing and untargeted metabolomics. The lung microbiome diversity, particularly its evenness, was increased (p = 0.044) and the microbiome profiles were different between individuals before and after therapy (PERMANOVA F=1.92, p=0.044). Despite these changes, the microbiomes were more similar within an individual than across the sampled population. There were no specific microbial taxa that were different in abundance before and after therapy, but collectively, the log-ratio of anaerobes to pathogens significantly decreased. The sputum metabolome also showed changes due to TKT. Beta-diversity increased after therapy (PERMANOVA F=4.22, p=0.022) and was characterized by greater variation across subjects while on treatment. This significant difference in the metabolome was driven by a decrease in peptides, amino acids, and metabolites from the kynurenine pathway. Metabolism of the three small molecules that make up TKT was extensive, including previously uncharacterized structural modifications. This study shows that TKT therapy affects both the microbiome and metabolome of airway mucus. This effect was stronger on sputum biochemistry, which may reflect changing niche spaces for microbial residency in lung mucus as the drug effects take hold, which then leads to changing microbiology.

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yan Hui ◽  
Paulina Tamez-Hidalgo ◽  
Tomasz Cieplak ◽  
Gizaw Dabessa Satessa ◽  
Witold Kot ◽  
...  

Abstract Background The direct use of medical zinc oxide in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders. Results This study investigated the effect of using rapeseed-seaweed blend (rapeseed meal added two brown macroalgae species Ascophylum nodosum and Saccharina latissima) fermented by lactobacilli (FRS) as feed ingredients in piglet weaning. From d 28 of life to d 85, the piglets were fed one of three different feeding regimens (n = 230 each) with inclusion of 0%, 2.5% and 5% FRS. In this period, no significant difference of piglet performance was found among the three groups. From a subset of piglets (n = 10 from each treatment), blood samples for hematology, biochemistry and immunoglobulin analysis, colon digesta for microbiome analysis, and jejunum and colon tissues for histopathological analyses were collected. The piglets fed with 2.5% FRS manifested alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier relative to the 0% FRS group. The colon microbiota composition was determined using V3 and V1-V8 region 16S rRNA gene amplicon sequencing by Illumina NextSeq and Oxford Nanopore MinION, respectively. The two amplicon sequencing strategies showed high consistency between the detected bacteria. Both sequencing strategies indicated that inclusion of FRS reshaped the colon microbiome of weaned piglets with increased Shannon diversity. Prevotella stercorea was verified by both methods to be more abundant in the piglets supplied with FRS feed, and its abundance was positively correlated with colonic mucosa thickness but negatively correlated with blood concentrations of leucocytes and IgG. Conclusions FRS supplementation relieved the gut lymphocyte infiltration of the weaned piglets, improved the colon mucosa barrier with altered microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not lead to further improvements.


2020 ◽  
Vol 8 (4) ◽  
pp. 547
Author(s):  
Martina Troll ◽  
Stefan Brandmaier ◽  
Sandra Reitmeier ◽  
Jonathan Adam ◽  
Sapna Sharma ◽  
...  

The analysis of the gut microbiome with respect to health care prevention and diagnostic purposes is increasingly the focus of current research. We analyzed around 2000 stool samples from the KORA (Cooperative Health Research in the Region of Augsburg) cohort using high-throughput 16S rRNA gene amplicon sequencing representing a total microbial diversity of 2089 operational taxonomic units (OTUs). We evaluated the combination of three different components to assess the reflection of obesity related to microbiota profiles: (i) four prediction methods (i.e., partial least squares (PLS), support vector machine regression (SVMReg), random forest (RF), and M5Rules); (ii) five OTU data transformation approaches (i.e., no transformation, relative abundance without and with log-transformation, as well as centered and isometric log-ratio transformations); and (iii) predictions from nine measurements of obesity (i.e., body mass index, three measures of body shape, and five measures of body composition). Our results showed a substantial impact of all three components. The applications of SVMReg and PLS in combination with logarithmic data transformations resulted in considerably predictive models for waist circumference-related endpoints. These combinations were at best able to explain almost 40% of the variance in obesity measurements based on stool microbiota data (i.e., OTUs) only. A reduced loss in predictive performance was seen after sex-stratification in waist–height ratio compared to other waist-related measurements. Moreover, our analysis showed that the contribution of OTUs less prevalent and abundant is minor concerning the predictive power of our models.


2020 ◽  
Vol 99 (6) ◽  
pp. 703-712 ◽  
Author(s):  
V.C. de Jesus ◽  
R. Shikder ◽  
D. Oryniak ◽  
K. Mann ◽  
A. Alamri ◽  
...  

Severe early childhood caries (S-ECC) is a multifactorial disease that can lead to suffering and reduced oral health–related quality of life in young children. The bacterial and fungal composition of dental plaque and how children’s sex is associated with S-ECC are largely unknown. In this study, V4-16S rRNA and ITS1 rRNA gene amplicon sequencing was used to compare the plaque bacteriome and mycobiome of children <72 mo of age: 40 with S-ECC (15 males, 25 females) and 40 caries-free (19 males, 21 females). Health- and nutrition-related questionnaire data were also investigated. This study aimed to analyze potential sex-based differences in the supragingival plaque microbiota of young children with S-ECC and those caries-free. Behavioral and nutritional habit differences were observed between children with S-ECC and those caries-free and between male and female children. Overall, higher levels of Veillonella dispar, Streptococcus mutans, and other bacterial species were found in the S-ECC group as compared with caries-free controls ( P < 0.05). A significant difference in the abundance of Neisseria was observed between males and females with S-ECC ( P < .05). Fungal taxonomic analysis showed significantly higher levels of Candida dubliniensis in the plaque of children with S-ECC as compared with those caries-free ( P < 0.05), but no differences were observed with Candida albicans ( P > 0.05). Significant differences in the relative abundance of Mycosphaerella, Cyberlindnera, and Trichosporon fungal species were also observed between the caries-free and S-ECC groups ( P < 0.05). Machine learning analysis revealed the most important bacterial and fungal species for classifying S-ECC versus caries-free. Different patterns of crosstalk between microbial species were observed between male and female children. Our work demonstrates that plaque microbiota and sex may be important determinants for S-ECC and could be factors to consider for inclusion in caries risk assessment tools.


Digestion ◽  
2021 ◽  
pp. 1-9
Author(s):  
Yoshihiko Kono ◽  
Ryo Inoue ◽  
Takumi Teratani ◽  
Mineyuki Tojo ◽  
Yuko Kumagai ◽  
...  

<b><i>Background/Aims:</i></b> Recent studies have demonstrated that the populations of several microbes are significantly increased in fecal samples from patients with colorectal cancer (CRC), suggesting their involvement in the development of CRC. The aim of this study was to identify microbes which are increased in distal CRCs and to identify the specific location of microbes increased in mucosal tissue around the tumor. <b><i>Methods:</i></b> Tissue specimens were collected from surgical resections of 28 distal CRCs. Five samples were collected from each specimen (location A: tumor, B: adjacent normal mucosa, C: normal mucosa 1 cm proximal to the tumor, D: normal mucosa 3 cm proximally, and E: normal mucosa 6 cm proximally). The microbiota in the sample were analyzed using 16S rRNA gene amplicon sequencing and the relative abundance (RA) of microbiota compared among the 5 locations. <b><i>Results:</i></b> At the genus level, the RA of <i>Fusobacterium</i> and <i>Streptococcus</i> at location A was the highest among the 5 locations, significantly different from that in location E. The dominant species of each genus was <i>Fusobacterium nucleatum</i> and <i>Streptococcus anginosus.</i> The RAs of these species gradually decreased from locations B to E with a statistically significant difference in <i>F. nucleatum</i>. The genus <i>Peptostreptococcus</i> also showed a similar trend, and the RA of <i>Peptostreptococcus stomatis</i> in location A was significantly associated with depth of tumor invasion and tumor size. <b><i>Conclusion:</i></b> Although the clinical relevance is not clear yet, these results suggest that <i>F. nucleatum, S. anginosus</i>, and <i>P. stomatis</i> can spread to the adjacent normal tissues and may change the surrounding microenvironment to support the progression of CRC.


2020 ◽  
Vol 53 (1) ◽  
Author(s):  
Bui Phan Thu Hang ◽  
Ewa Wredle ◽  
Johan Dicksved

AbstractThe aim of this study was to characterize the colostrum and fecal microbiota in calves and to investigate whether fecal microbiota composition was related to colostrum microbiota or factors associated with calf health. Colostrum samples were collected in buckets after hand milking of 76 calving cows from 38 smallholder dairy farms. Fecal samples were taken directly from the rectum of 76 calves at birth and at 14 days age. The bacterial community structure in colostrum and feces was analyzed by terminal restriction fragment length polymorphism for all samples, and the microbial composition was determined by 16S rRNA gene amplicon sequencing for a subset of the samples (8 colostrum, 40 fecal samples). There was a significant difference in fecal microbiota composition between day 0 and day 14 samples, but no associations between the microbiota and average daily gain, birth weight, or transfer of passive immunity. At 14 days of age, Faecalibacterium and Butyricicoccus were prevalent in higher relative abundances in the gut of healthy calves compared to calves with diarrhea that had been treated with antimicrobials. Colostrum showed great variation in composition of microbiota but no association to fecal microbiota. This study provides the first insights into the composition of colostrum and fecal microbiota of young dairy calves in southern Vietnam and can form the basis for future more detailed studies.


Biology ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 31
Author(s):  
Jianbo Zhang ◽  
Peng Wang ◽  
Renqing Dingkao ◽  
Mei Du ◽  
Anum Ali Ahmad ◽  
...  

Background: The gut microbiota plays an important role in the health and production of animals. However, little information is available on the dynamic variations and comparison of intestinal microbiota in post-weaning yak calves living on the QTP. Methods: We explored the fecal bacterial microbiota succession of yak calves at different months after early weaning (60 d) compared with cattle calves by 16S rRNA gene amplicon sequencing and functional composition prediction. Results: We found no significant difference in blood biochemical parameters related to glucose and lipid metabolism between yaks and calves in different months after weaning. The core fecal bacterial microbiota from both species of calves was dominated by Ruminococcaceae, Rikenellaceae, and Bacteroidaceae. The fecal microbial community has a great alteration within the time after weaning in both cattle and yak calves, but cattle showed a larger change. After five months, the microbiota achieves a stable and concentrated state. This is also similar to the functional profile. Conclusions: Based on the exploration of dynamic changes in the fecal microbiota at an early stage of life, our results illustrated that there were no negative effects of intestinal microbiota succession on yak calves when early weaning was employed.


2021 ◽  
Vol 67 (3) ◽  
pp. 144-154
Author(s):  
Hafeez Ul Haq ◽  
Ye Li ◽  
Lingyue Jin ◽  
Ting Zhang ◽  
Linjie Cheng ◽  
...  

Abstract The frequent use of chemical fertiliser produces harmful effects on the soil ecosystem. Therefore, biocompatible methods are used to improve plant health and production through natural fertiliser or plant beneficial microorganisms. This study aims to investigate the effect of amended chicken manure-based natural fertiliser on bacterial communities and plant beneficial bacteria of tomato endosphere microbiome using the high throughput 16S rRNA gene amplicon sequencing. The results showed Proteobacteria (89.4 ± 4.7% to 86.7 ± 3.9%), Actinobacteria (6.03 ± 2.9% to 3.56 ± 2.1%), and Firmicutes (3.34 ± 1.3% to 0.59 ± 0.3%) as the dominant bacterial phyla of tomato endophytic microbiome. Pseudomonas and Bacillus were the most abundant identifiable genera in the chicken manure root (CMR) (amended manure treatments) sample. There was no significant difference in alpha bacterial diversity (Shannon index: p = 0.48) and species richness (Chao 1: p = 0.43) between control original root (OR) and CMR. However, the distribution of the dominant phyla was mainly affected by manure fertilisation. The non-metric multidimensional scaling (NMDS) and PCoA of beta diversity analysis suggested a significant separation in bacterial communities of tomato endophytes between CMR and OR. The most differently abundant bacterial taxa belong to Bacteroidetes in the OR group, whereas the beneficial bacterial communities of Actinobacteria and Firmicutes were more abundant in the CMR group. Therefore, the chicken manure application can significantly affect bacterial communities of tomatoes´ root endophytic microbiome and effectively improve the abundance of the beneficial microbes as biofertilisers.


Author(s):  
A. E. Chernikova ◽  
Yu. P. Potekhina

Introduction. An osteopathic examination determines the rate, the amplitude and the strength of the main rhythms (cardiac, respiratory and cranial). However, there are relatively few studies in the available literature dedicated to the influence of osteopathic correction (OC) on the characteristics of these rhythms.Goal of research — to study the influence of OC on the rate characteristics of various rhythms of the human body.Materials and methods. 88 adult osteopathic patients aged from 18 to 81 years were examined, among them 30 men and 58 women. All patients received general osteopathic examination. The rate of the cranial rhythm (RCR), respiratory rate (RR) heart rate (HR), the mobility of the nervous processes (MNP) and the connective tissue mobility (CTM) were assessed before and after the OC session.Results. Since age varied greatly in the examined group, a correlation analysis of age-related changes of the assessed rhythms was carried out. Only the CTM correlated with age (r=–0,28; p<0,05) in a statistically significant way. The rank dispersion analysis of Kruskal–Wallis also showed statistically significant difference in this indicator in different age groups (p=0,043). With the increase of years, the CTM decreases gradually. After the OC, the CTM, increased in a statistically significant way (p<0,0001). The RCR varied from 5 to 12 cycles/min in the examined group, which corresponded to the norm. After the OC, the RCR has increased in a statistically significant way (p<0,0001), the MNP has also increased (p<0,0001). The initial heart rate in the subjects varied from 56 to 94 beats/min, and in 15 % it exceeded the norm. After the OC the heart rate corresponded to the norm in all patients. The heart rate and the respiratory rate significantly decreased after the OC (р<0,0001).Conclusion. The described biorhythm changes after the OC session may be indicative of the improvement of the nervous regulation, of the normalization of the autonomic balance, of the improvement of the biomechanical properties of body tissues and of the increase of their mobility. The assessed parameters can be measured quickly without any additional equipment and can be used in order to study the results of the OC.


2018 ◽  
Vol 1 ◽  
pp. 107
Author(s):  
Adi Heryadi ◽  
Evianawati Evianawati

This study aims to prove whether transformational leadership training is effective for building anti-corruption attitudes of villages in Kebonharjo village, subdistrict Samigaluh Kulonprogo. This research is an experimental research with one group pre and posttest design.Subject design is 17 people from village of 21 candidates registered. Measuring tool used in this research is the scale of anti-corruption perception made by the researcher referring to the 9 anti-corruption values with the value of reliability coefficient of 0.871. The module used as an intervention made by the researcher refers to the transformational leadership dimension (Bass, 1990). The data collected is analyzed by statistical analysis of different test Paired Sample Test. Initial data collection results obtained sign value of 0.770 which means> 0.05 or no significant difference between anti-corruption perception score between before and after training. After a period of less than 1 (one) month then conducted again the measurement of follow-up of the study subjects in the measurement again using the scale of anti-corruption perception. The results of the second data collection were analysed with Paired Samples Test and obtained the value of 0.623 sign meaning p> 0.05 or no significant difference between post test data with follow-up data so that the hypothesis of this study was rejected.


Author(s):  
Sanjeeva Kumar Goud T ◽  
Rahul Kunkulol

The present study was aimed to study the effect of Sublingual Vitamin D3 on Serum Vitamin D level in Vitamin D deficiency patients. This was a cross-sectional and interventional study. All the Vitamin D deficiency patients of age 18-60years and either gender, willing to participate in the study were included. Patients who had greater than 20 ng/ml were excluded from the study. The total number of participants in our study was 200, out of these 111 males and 89 females, the mean age in our study was 51.07 ± 7.39Yrs. All volunteers were given sublingual vitamin D3 (60,000IU) in six doses every fifteen days of follow up for 3 months. The subject’s serum 25(OH)D levels were estimated before and after the treatment of sublingual vitamin D3. There was a statistically significant difference in serum vitamin D3 level before 16.61±6.71 ng/ml and after 35.80±7.80 ng/ml after treatment with Sublingual Vitamin D3. Six doses of 60,000IU of Vitamin D3 sublingual route having improved the role of serum 25(OH)D levels in the treatment of Vitamin D3 deficiency patients.Keywords: Vitamin D3; Sublingual route


Sign in / Sign up

Export Citation Format

Share Document