Age-Matching in Pediatric Fecal Matter Transplants.
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ABSTRACT:
SUBMITTER: MacLellan AD
PROVIDER: S-EPMC8322514 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Age-Matching in Pediatric Fecal Matter Transplants.
MacLellan Abigale D AD Finlay B Brett BB Appel-Cresswell Silke S
Frontiers in pediatrics 20210716
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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:The human intestine harbors a huge number of diverse microorganisms where a variety of complex interactions take place between the microbes as well as the host and gut microbiota. Significant long-term variations in the gut microbiota (dysbiosis) have been associated with a variety of health conditions including inflammatory bowel disease (IBD). Conventional fecal microbiota transplantations (FMTs) have been utilized to treat IBD and have been proved promising. However, various limitations such as transient results, pathogen transfer, storage, and reproducibility render conventional FMT less safe and less sustainable. Defined synthetic microbial communities (SynCom) have been used to dissect the host-microbiota-associated functions using gnotobiotic animals or in vitro cell models. This review focuses on the potential use of SynCom in IBD and its advantages and relative safety over conventional FMT. Additionally, this review reinforces how various technological advances could be combined with SynCom to have a better understanding of the complex microbial interactions in various gut inflammatory diseases including IBD. Some technological advances including the availability of a gut-on-a-chip system, intestinal organoids, ex vivo intestinal cultures, AI-based refining of the microbiome structural and functional data, and multiomic approaches may help in making more practical in vitro models of the human host. Additionally, an increase in the cultured diversity from gut microbiota and the availability of their genomic information would further make the design and utilization of SynCom more feasible. Taken together, the combined use of the available knowledge of the gut microbiota in health and disease and recent technological advances and the development of defined SynCom seem to be a promising, safe, and sustainable alternative to conventional FMT in treating IBD.
| S-EPMC8820897 | 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: Not available
| S-EPMC11444755 | 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:Burgeoning study of host-associated microbiomes has accelerated the development of microbial therapies, including fecal microbiota transplants (FMTs). FMTs provide host-specific microbial supplementation, with applicability across host species. Studying FMTs can simultaneously provide comparative frameworks for understanding microbial therapies in diverse microbial systems and improve the health of managed wildlife. Ex-situ carnivores, including cheetahs (Acinonyx jubatus), often suffer from intractable gut infections similar to those treated with antibiotics and FMTs in humans, providing a valuable system for testing FMT efficacy. Using an experimental approach in 21 cheetahs, we tested whether autologous FMTs facilitated post-antibiotic recovery of gut microbiota. We used 16S rRNA sequencing and microbial source tracking to characterize antibiotic-induced microbial extirpations and signatures of FMT engraftment for single versus multiple FMTs. We found that antibiotics extirpated abundant bacteria and FMTs quickened post-antibiotic recovery via engraftment of bacteria that may facilitate protein digestion and butyrate production (Fusobacterium). Although multiple FMTs better sustained microbial recovery compared to a single FMT, one FMT improved recovery compared to antibiotics alone. This study elucidated the dynamics of microbiome modulation in a non-model system and improves foundations for reproducible, low-cost, low-dose, and minimally invasive FMT protocols, emphasizing the scientific and applied value of FMTs across species.
| S-EPMC11666765 | biostudies-literature
Project description:BackgroundFecal microbiota transplantation (FMT) and fecal virome transplantation (FVT, sterile filtrated donor feces) have been effective in treating recurrent Clostridioides difficile infections, possibly through bacteriophage-mediated modulation of the gut microbiome. However, challenges like donor variability, costly screening, coupled with concerns over pathogen transfer (incl. eukaryotic viruses) with FMT or FVT hinder their wider clinical application in treating less acute diseases.MethodsTo overcome these challenges, we developed methods to broaden FVT's clinical application while maintaining efficacy and increasing safety. Specifically, we employed the following approaches: (1) chemostat-fermentation to reproduce the bacteriophage FVT donor component and remove eukaryotic viruses (FVT-ChP), (2) solvent-detergent treatment to inactivate enveloped viruses (FVT-SDT), and (3) pyronin-Y treatment to inhibit RNA virus replication (FVT-PyT). We assessed the efficacy of these processed FVTs in a C. difficile infection mouse model and compared them with untreated FVT (FVT-UnT), FMT, and saline.ResultsFVT-SDT, FVT-UnT, and FVT-ChP reduced the incidence of mice reaching the humane endpoint (0/8, 2/7, and 3/8, respectively) compared to FMT, FVT-PyT, and saline (5/8, 7/8, and 5/7, respectively) and significantly reduced the load of colonizing C. difficile cells and associated toxin A/B levels. There was a potential elimination of C. difficile colonization, with seven out of eight mice treated with FVT-SDT testing negative with qPCR. In contrast, all other treatments exhibited the continued presence of C. difficile. Moreover, the results were supported by changes in the gut microbiome profiles, cecal cytokine levels, and histopathological findings. Assessment of viral engraftment following FMT/FVT treatment and host-phage correlations analysis suggested that transfer of phages likely were an important contributing factor associated with treatment efficacy.ConclusionsThis proof-of-concept study shows that specific modifications of FVT hold promise in addressing challenges related to donor variability and infection risks. Two strategies lead to treatments significantly limiting C. difficile colonization in mice, with solvent/detergent treatment and chemostat propagation of donor phages emerging as promising approaches. Video Abstract.
| S-EPMC11218093 | biostudies-literature
Project description:IntroductionAntibiotic resistant bacterial infections (ARBIs) are extremely common in nursing home residents. These infections typically occur after a course of antibiotics, which eradicate both pathological and beneficial organisms. The eradication of beneficial organisms likely facilitates subsequent ARBIs. Autologous fecal microbiota transplant (aFMT) has been proposed as a potential treatment to reduce ARBIs in nursing home residents. Our objective was to determine the feasibility and safety of aFMT in a nursing home population.MethodsPilot clinical trial. We evaluated feasibility as total number of stool samples collected for aFMT production and safety as the number and relatedness of serious (SAE) and non-serious adverse events (AE).ResultsWe screened 468 nursing home residents aged ≥18 years for eligibility; 67 enrolled, distributed among three nursing homes. Participants were 62.7% female and 35.8% Black. Mean age was 82.2 ± 8.5 years. Thirty-three participants underwent successful stool collection. Seven participants received antibiotics; four participants underwent aFMT. There were 40 SAEs (17 deaths) and 11 AEs. In the aFMT group, there were 3 SAEs (2 deaths) and 10 AEs. All SAEs and AEs were judged unrelated to the study intervention.ConclusionsIn this pilot study of aFMT in nursing home residents, less than half were able to provide adequate stool samples for aFMT. There were no related SAEs or AEs during the study. In sum, we conclude aFMT has limited feasibility in a nursing home population due to logistic and technical challenges but is likely safe.Trial registrationClinicalTrials.gov Identifier: NCT03061097.
| S-EPMC8921299 | biostudies-literature