Age-Matching in Pediatric Fecal Matter Transplants.
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ABSTRACT:
SUBMITTER: MacLellan AD
PROVIDER: S-EPMC8322514 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:IntroductionAlthough fecal microbiota transplantation (FMT) is a recommended, clinically efficacious, and cost-effective treatment for recurrent Clostridioides difficile infection (CDI), the scale of FMT use in the United States is unknown.MethodsWe developed a population-level CDI model.ResultsWe estimated that 48,000 FMTs could be performed annually, preventing 32,000 CDI recurrences.DiscussionImproving access to FMT could lead to tens of thousands fewer C. difficile episodes per year.
| S-EPMC7594930 | biostudies-literature
Project description:BackgroundEven in the modern era of kidney transplantation with improved surgical techniques, immunosuppression, and clinical care, HLA matching has been shown to be important in allograft survival in adults who receive an organ from either a deceased or living donor. We now explore the impact of genetic matching in pediatric first-kidney transplants.MethodsUsing the United Network for Organ Sharing data, we identified 18 602 first pediatric (<18 years) kidney transplants between October 1, 1987, and December 31, 2016. Recipients were classified by number of HLA mismatches and donor origin. Cox proportional hazard analyses, adjusting for recipient and donor transplant covariates, were performed to study the impact of HLA on kidney allograft survival.ResultsFor the fully adjusted Cox model there was a 30% increase in the hazard of allograft failure for 1 HLA mismatch, when compared with 0 mismatched recipients, and a 92% increase in risk for 6 mismatches. Although pediatric allografts from living donors survive as long or longer than those from deceased persons, they have a higher hazard of failure as a function of HLA mismatch. Kidney allografts from deceased donors HLA mismatched 0 to 3 were found to survive as long as organs from living donors HLA mismatched 4 to 6. In the full Cox model, there was a strong, linear effect on the hazard of allograft failure with quartile of age such that the youngest patients at age of transplant had the longest surviving grafts.ConclusionsHLA plays an important role in the survival of first pediatric kidney transplants. The better the match, and the earlier the transplant is performed in the child's life, the lower is the risk that the organ will fail.
| S-EPMC6056273 | biostudies-literature
Project description:BackgroundReduced microbiota diversity (dysbiosis) in people with HIV (PWH) likely contributes to inflammation, a driver of morbidity and mortality. We aimed to evaluate the safety and tolerability of 6 weekly oral fecal microbiota transplants (FMT) administered to reverse this dysbiosis.MethodsSix PWH on suppressive antiretroviral therapy (ART) received 6 weekly doses of lyophilized fecal microbiota product from healthy donors. Shotgun sequencing on stool before, after last FMT, and 20 weeks thereafter was performed. Inflammation and gut permeability biomarkers were measured.ResultsMedian age at week 0 was 39 years, CD4+ T cell count 496 cells/mm3, HIV RNA levels <20 copies/mL. FMT was safe and well-tolerated. α diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest α diversity at week 0. At week 26, α diversity more closely resembled week 0 than week 6 in these 4 participants. Metagenomic analysis showed no consistent changes across all participants. One participant had high gut permeability and inflammation biomarker levels and low α diversity that improved between weeks 0 and 6 with a shift in distribution.ConclusionsWeekly FMT was safe and well-tolerated. α diversity increased in participants with the lowest baseline α diversity during the treatment period. Future randomized, controlled trials of FMT should consider evaluating PWH with greater inflammation, gut damage, or dysbiosis as this population may be most likely to show a significant response.ClinicalTrials.gov Identifier: NCT03329560.
| S-EPMC7815055 | biostudies-literature
Project description:Recurrent Clostridium difficile infection (RCDI) is associated with repeated antibiotic treatment and the enhanced growth of antibiotic-resistant microbes. This study tested the hypothesis that patients with RCDI would harbor large numbers of antibiotic-resistant microbes and that fecal microbiota transplantation (FMT) would reduce the number of antibiotic-resistant genes.In a single center study, patients with RCDI (n = 20) received FMT from universal donors via colonoscopy. Stool samples were collected from donors (n = 3) and patients prior to and following FMT. DNA was extracted and shotgun metagenomics performed. Results as well as assembled libraries from a healthy cohort (n = 87) obtained from the Human Microbiome Project were aligned against the NCBI bacterial taxonomy database and the Comprehensive Antibiotic Resistance Database. Results were corroborated through a DNA microarray containing 354 antibiotic resistance (ABR) genes.RCDI patients had a greater number and diversity of ABR genes compared with donors and healthy controls. Beta-lactam, multidrug efflux pumps, fluoroquinolone, and antibiotic inactivation ABR genes were increased in RCDI patients, although donors primarily had tetracycline resistance. RCDI patients were dominated by Proteobacteria with Escherichia coli and Klebsiella most prevalent. FMT resulted in a resolution of symptoms that correlated directly with a decreased number and diversity of ABR genes and increased Bacteroidetes and Firmicutes with reduced Proteobacteria. ABR gene profiles were maintained in recipients for up to a year following FMT.RCDI patients have increased numbers of antibiotic-resistant organisms. FMT is effective in the eradication of pathogenic antibiotic-resistant organisms and elimination of ABR genes.
| S-EPMC4885654 | biostudies-other
Project description:The intestinal microbiota and its functions are intricately interwoven with host physiology. Colonizing rodents with donor microbiota provides insights into host-microbiota interactions characterization and the understanding of disease physiopathology. However, a better assessment of inoculation methods and recipient mouse models is needed. Here, we compare the engraftment at short and long term of genetically obese mice microbiota in germ-free (GF) mice and juvenile and adult specific pathogen free (SPF) mice. We also tested the effects of initial microbiota depletion before microbiota transfer. In the present work, donor microbiota engraftment was better in juvenile SPF mice than in adult SPF mice. In juvenile mice, initial microbiota depletion using laxatives or antibiotics improved donor microbiota engraftment 9 weeks but not 3 weeks after microbiota transfer. Microbiota-depleted juvenile mice performed better than GF mice 3 weeks after the microbiota transfer. However, 9 weeks after transfer, colonized GF mice microbiota had the lowest Unifrac distance to the donor microbiota. Colonized GF mice were also characterized by a chronic alteration in intestinal absorptive function. With these collective results, we show that the use of juvenile mice subjected to initial microbiota depletion constitutes a valid alternative to GF mice in microbiota transfer studies.
| S-EPMC6339881 | biostudies-literature
Project description:Fecal matter from Boss taurus Raw sequence reads
| PRJNA588733 | ENA
Project description:This study examined the functional response of a host (zebrafish) to implantation of a conspecific or allospecific (goldfish) gastrointestinal (GIT) microbiome followed by diet manipulation and the repercussions of these manipulations on host GIT physiology. Implantation of a native zebrafish biome successfully reintroduced wildtype (WT) communities with the exception of several rare, phylogenetically distant species. Implantation of a foreign goldfish biome created communities that were distinct from WT, suggesting that the seeding community created substantial differences from the native host communities. A mismatched ?natural? diet and an implanted allospecific biome enriched for rarer and more phylogenetically diverse bacteria. Transcriptional changes within the GIT clustered in relationship to biome treatments, mirroring clustering of biome implants. Implantation of an allospecific biome along with an altered diet markedly down-regulated approximately 70% of the transcripts involved in cholesterol biosynthesis, while tissue content analysis revealed an increase in total tissue cholesterol. Furthermore, transcripts involved in lipogenesis pathways were significantly downregulated and correlated with a striking decrease in intestinal lipase activity driven by both biome and diet. Glucose-6P dehydrogenase (G6PD) activities increased during dietary manipulations regardless of biome, while the allospecific biome down-regulated transcripts involved in gluconeogenesis and altered glucokinase (GK) and hexokinase (HK) activities regardless of diet. However, growth rates did not reveal an impact of these responses. Adult zebrafish are unable to reform proportional representation within bacterial communities following transplantation of an allospecific biome resulting in transcriptional and enzymatic alterations for lipid and carbohydrate metabolism that did not affect overall animal homeostasis.
2018-08-30 | GSE118496 | GEO
Project description:As the importance of the gut microbiota in health and disease is a subject of growing interest, fecal microbiota transplantation (FMT) was suggested as an attractive therapeutic strategy to restore homeostasis of the gut microbiota, thereby treating diseases that were associated with alteration of the gut microbiota. FMT involves the administration of fresh, frozen, or dried fecal microorganisms from the gut of a healthy donor into the intestinal tract of a patient. This rediscovery of the potential benefits of an ancient practice was accompanied by a rapid progression of our understanding of the roles and mechanisms of gut microbes in the pathogenesis of disease. With a growing number of diseases being associated with dysbiosis or the alteration of gut microbiota, FMT was suggested as an attractive therapeutic strategy to "reset the gut" and initiate clinical resolutions or remissions. The number of FMT clinical trials is increasing worldwide, but no trials are registered in the Gulf region; this suggested the need for raising awareness of the latest studies on FMT. This review presented the emergent preclinical and clinical data to give an overview of the potential clinical applications, the benefits, and inconveniences that were worth considering for eventual future testing of fecal transplants in Qatar and the Middle East. This study highlighted the diversity of methods tested and commented on the variables that can affect the assessment of the effectiveness of FMT in specific diseases. The risks associated with FMT and the threat of antimicrobial resistance for this therapeutic approach were reviewed. From gastrointestinal diseases to neurodevelopmental disorders, understanding the roles of the gut microbiota in health and disease should be at the heart of developing novel, standardized, yet personalized, methods for this ancient therapeutic approach.
| S-EPMC8475724 | biostudies-literature
Project description:Long term erythropoietic reconstitution after allogeneic hematopoietic stem cell transplantation (alloHSCT) has not been extensively studied. We aimed to describe erythropoietic reconstitution as an indicator of long-term graft function by modeling hemoglobin levels during the first 3 years post HSCT in pediatric patients. We retrospectively included 414 patients and 11,957 measurements. The largest hemoglobin increase was at day 45 and levels reached a steady state at day 648 with a level of 7.48 mmol/L. In patients transplanted for hematological malignancies hemoglobin levels normalized faster (p < 0.0001). Increasing patient age correlated with faster recovery (p < 0.0001), while donor age had no influence. Conditioning, donor type and graft source did not influence recovery significantly. In the ABO mismatched group there was a transient negative effect on hemoglobin levels, and a delay in reticulocyte recovery (21 vs. 19 days; p = 0.012). In contrast, hemoglobin levels reached a higher plateau beyond 9 months in these patients (p < 0.0001). After alloHSCT, experiencing a CMV reactivation negatively affected reconstitution (p = 0.034), while EBV reactivations and acute graft vs. host disease did not. In summary, erythropoietic recovery was mainly influenced by patient factors and primary disease, and less influenced by donor factors.
| S-EPMC7734089 | biostudies-literature
Project description:DNA methylation (DNAm) plays diverse roles in human biology, but this dynamic epigenetic mark remains far from fully characterized. Although earlier studies uncovered loci that undergo age-associated DNAm changes in adults, little is known about such changes during childhood. Despite profound DNAm plasticity during embryogenesis and early development, monozygotic twins show indistinguishable childhood methylation, suggesting DNAm is highly coordinated during the pediatric period. Here we examine the methylation of 27,578 CpG dinucleotides in peripheral blood DNA from 398 boys, aged 3 to 17 years, and find significant age-associated changes in DNAm at 2,078 loci. We report a deficit of such loci on the X chromosome, a preference for specific nucleotides immediately surrounding the interrogated CpG dinucleotide, and a primary association with developmental and immune ontological functions. These pediatric age-associated loci overlap significantly with those previously identified in adults (p < 0.001) but most of the pediatric loci are unique, suggesting many are childhood-specific. Meta-analysis (n = 1080) with two adult studies reveals that the methylation changes in 29.5% of the age-associated pediatric loci follow a linear pattern from childhood into adulthood; however, we also find a three-fold higher rate of change in children compared with adults and that a higher proportion of lifelong changes are more accurately modeled as a function of logarithmic age. We therefore conclude that DNAm changes occur more rapidly during childhood and are imperfectly accounted for by statistical corrections that are linear in age, further suggesting that future DNAm studies are matched closely for age. Age associated DNA methylation was evaluated at each CpG locus using a fixed-effects linear regression model adjusting for BeadChip as a covariate to account for batch effects. Analysis of variance (ANOVA) was conducted for each CpG locus to assess the age affect at each CpG locus which was subsequently corrected for multiple hypotheses using a Benjamini-Hochberg FDR. SUPPLEMENTARY FILES: * Matrix_AllSampleDetection.txt: Detection P-values for each sample and each loci * Matrix_AllSampleSignal.txt: Signal for Probe A and Probe B for each sample and each loci * Matrix_Non-Normalized_AllSampleBeta.txt: Beta values calculated using GenomeStudio v2010.3 Methylation Module 1.8.5 as Signal of Probe B / (Signal of Probe A + Signal of Probe B + 100) * Matrix_Normalized_AllSampleBetaPrime.txt: Beta Prime values used for analysis calculated from the Probe B and Probe A signals as Beta Prime = Signal of Probe B / (Signal of Probe A + Signal of Probe A)
2012-02-01 | E-GEOD-27097 | biostudies-arrayexpress