scholarly journals Lower endoscopic delivery of freeze-dried intestinal microbiota results in more rapid and efficient engraftment than oral administration

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Christopher Staley ◽  
Hossam Halaweish ◽  
Carolyn Graiziger ◽  
Matthew J. Hamilton ◽  
Amanda J. Kabage ◽  
...  

AbstractFecal microbiota transplantation (FMT) is a highly effective treatment for recurrent Clostridioides difficile infection (rCDI). However, standardization of FMT products is essential for its broad implementation into clinical practice. We have developed an oral preparation of freeze-dried, encapsulated microbiota, which is ~ 80% clinically effective, but results in delayed engraftment of donor bacteria relative to administration via colonoscopy. Our objective was to measure the engraftment potential of freeze-dried microbiota without the complexity of variables associated with oral administration. We compared engraftment of identical preparations and doses of freeze-dried microbiota following colonoscopic (9 patients) versus oral administration (18 patients). Microbiota were characterized by sequencing of the 16S rRNA gene, and engraftment was determined using the SourceTracker algorithm. Oligotyping analysis was done to provide high-resolution patterns of microbiota engraftment. Colonoscopic FMT was associated with greater levels of donor engraftment within days following the procedure (ANOVA P = 0.035) and specific increases in the relative abundances of donor Lachnospiraceae, Bacteroidaceae, and Porphyromonadaceae (P ≤ 0.033). Lower relative abundances of Bacteroidaceae, Lachnospiraceae, and Ruminococcaceae families were associated with clinical failures. These results suggest that further optimization of oral capsule FMT may improve its engraftment efficiency and clinical efficacy.

2019 ◽  
Vol 73 ◽  
pp. 316-324
Author(s):  
Aleksandra Kwiatkowska ◽  
Karolina Skonieczna-Żydecka ◽  
Maria Marlicz ◽  
Wojciech Marlicz

The knowledge of the role of the digestive tract in human physiology and pathology has expanded tremendously in recent years. The human intestine is a habitat for a host complex of bacteria, fungi, viruses and Acheaea, all contributing to food digestion, fermentation, metabolism of xenobiotics as well as immune and neuroendocrine functions. Moreover, evidence is mounting that many environmental factors such as diet, drugs, stress and infection may potentially disrupt intestinal microbial milieu. Therefore, methods aimed to modulate gut microbiota are eagerly investigated and applied into daily clinical practice. Fecal microbiota transplantation (FMT) is a transplant of gut bacteria from a healthy donor to a recipent. Usually, the stool bacteria are introduced by means of colonoscopy, gastroduodenoscopy, enema, orogastric tube or orally in the form of a capsule containing freeze-dried material. The effectivness of FMT in the treatment of recurrent Clostridioides difficile infection (CDI) has been confirmed in a numer of high quality studies and is currently recommended as evidence-based therapy in clinical settings. However, FMT is promising in the treatment of other diseases, as it has proven to be an effective method of treating ulcerative colitis (UC) and is of promise in treating Crohn’s disease (CD), metabolic and neuropsychiatric disorders. Many questions related to FMT remain unanswered. A better understanding of fecal and mucosal microbial composition is needed, followed by the optimisation of regulatory issues and selection of best possible donor. Novel protocols based on a new class of probiotics as emerging alternatives to FMT in CDI are also briefly disscussed.


mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Christopher Staley ◽  
Thomas Kaiser ◽  
Byron P. Vaughn ◽  
Carolyn Graiziger ◽  
Matthew J. Hamilton ◽  
...  

ABSTRACT Fecal microbiota transplantation (FMT) has become a common rescue therapy for recurrent Clostridium difficile infection, and encapsulated delivery (cFMT) of healthy donor microbiota shows similar clinical efficacy as more traditional routes of administration. In this study, we characterized long-term patterns of bacterial engraftment in a cohort of 18 patients, who received capsules from one of three donors, up to 409 days post-FMT. Bacterial communities were characterized using Illumina sequencing of the V5-V6 hypervariable regions of the 16S rRNA gene, and engraftment was determined by using the Bayesian algorithm SourceTracker. All patients recovered clinically and were free of C. difficile infection following cFMT. The majority of patients (61%) showed high levels of engraftment after the first week following FMT, which were sustained throughout the year. A small subset, 22%, experienced a decline in donor engraftment after approximately 1 month, and a few patients (17%), two of whom were taking metformin, showed delayed and low levels of donor engraftment. Members of the genera Bacteroides, Parabacteroides, and Faecalibacterium were significantly and positively correlated with donor similarity (ρ = 0.237 to 0.373, P ≤ 0.017). Furthermore, throughout the year, patient fecal communities showed significant separation based on the donor fecal microbiota that they received (P < 0.001). Results of this study, which characterize long-term engraftment following cFMT, suggest that numerical donor similarity is not strictly related to clinical outcome and identify a persistent donor-specific effect on patient fecal microbial communities. Furthermore, results suggest that members of the Bacteroidetes may be important targets to improve engraftment via cFMT. IMPORTANCE Recurrent Clostridium difficile infection (rCDI) is the most common cause of hospital- and community-acquired diarrheal infection associated with antibiotic use. Fecal microbiota transplantation (FMT), a treatment that involves administration of fecal bacteria from a healthy donor to a recipient patient, is a highly effective rescue therapy for rCDI that is increasingly being incorporated into standard clinical practice. Encapsulated, freeze-dried preparations of fecal microbiota, administered orally, offer the simplest and most convenient route of FMT delivery for patients (cFMT). In this study, we evaluated the extent of bacterial engraftment following cFMT and the duration of donor bacterial persistence. All patients studied recovered clinically but showed differing patterns in long-term microbial community similarity to the donor that were associated with members of the bacterial group Bacteroidetes, previously shown to be prominent contributors to rCDI resistance. Results highlight long-lasting, donor-specific effects on recipient patient microbiota and reveal potential bacterial targets to improve cFMT engraftment.


2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S599-S599
Author(s):  
Curtis Donskey ◽  
Michelle Hecker ◽  
Christian Rosero

Abstract Background Background: Fecal microbiota transplantation (FMT) is effective for treatment of recurrent Clostridioides difficile infection (CDI). However, limited data are available on the durability of FMT, especially after FMT via capsules and with more than 1 year of follow-up. Figure. Outcomes after FMT in 162 patients with recurrent CDI Methods Methods: A retrospective cohort study was conducted for all patients undergoing FMT from April 2013–November 2020 in a tertiary care hospital. Initial management was considered successful if 1 to 3 FMTs resulted in improved symptoms with no diagnosis of recurrent CDI at 3 months after the initial FMT. Medical record review and telephone interviews were conducted to determine the frequency of recurrent CDI after initial successful management. Results Results: One-hundred sixty-two patients received 228 FMT procedures (range, 1 to 5), including 78 (34%) via colonoscopy, 144 (63%) via freeze-dried oral capsules, and 6 (3%) via nasogastric/duodenal/PEG tube. The median follow-up time after initial FMT was 61 months (range, 10 to 99 months). Initial management was successful in 132 (81%) patients after 1 FMT and in 24 (14%) patients with 1-2 additional FMTs (Figure). During long-term follow-up, 29 recurrences occurred in 22 of 159 (14%) patients evaluated. Ten (34%) of the recurrences occurred greater than 12 months after the initial FMT. Of the 22 patients with recurrence after 3 months, 16 (73%) were successfully managed with CDI therapy or additional FMT. Conclusion Conclusion: In our center, FMT via colonoscopy or freeze-dried capsules was very successful in initial management of recurrent CDI and 85% had a durable response with no further recurrences. However, more than 1 FMT procedure was often required to achieve initial success and to manage late recurrences. Disclosures All Authors: No reported disclosures


2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Fengqiong Liu ◽  
Shanliang Ye ◽  
Xin Zhu ◽  
Xuesong He ◽  
Shengzhou Wang ◽  
...  

Abstract Background To investigate the potential beneficial effect of fecal microbiota transplantation (FMT) on gastrointestinal symptoms, gut dysbiosis and immune status in discharged COVID-19 patients. Case presentation A total of 11 COVID-19 patients were recruited in April, 2020, about one month on average after they were discharged from the hospital. All subjects received FMT for 4 consecutive days by oral capsule administrations with 10 capsules for each day. In total, 5 out of 11 patients reported to be suffered from gastrointestinal symptoms, which were improved after FMT. After FMT, alterations of B cells were observed, which was characterized as decreased naive B cell (P = 0.012) and increased memory B cells (P = 0.001) and non-switched B cells (P = 0.012).The microbial community richness indicated by operational taxonomic units number, observed species and Chao1 estimator was marginally increased after FMT. Gut microbiome composition of discharged COVID-19 patients differed from that of the general population at both phylum and genera level, which was characterized with a lower proportion of Firmicutes (41.0%) and Actinobacteria (4.0%), higher proportion of Bacteroidetes (42.9%) and Proteobacteria (9.2%). FMT can partially restore the gut dysbiosis by increasing the relative abundance of Actinobacteria (15.0%) and reducing Proteobacteria (2.8%) at the phylum level. At the genera level, Bifidobacterium and Faecalibacterium had significantly increased after FMT. Conclusions After FMT, altered peripheral lymphocyte subset, restored gut microbiota and alleviated gastrointestinal disorders were observe, suggesting that FMT may serve as a potential therapeutic and rehabilitative intervention for the COVID-19.


2021 ◽  
Vol 14 (01) ◽  
pp. 016-020
Author(s):  
Juliana Peloso Signorette ◽  
Rômulo Tadeu Dias de Oliveira ◽  
José Maria Montiel ◽  
Priscila Larcher Longo

Abstract Objective This study aimed to perform a comprehensive review of clinical trials using fecal microbiota transplantation in cases of Clostridioides difficile infection. Methods This manuscript reviews clinical studies published from 2003 to 2020 at the Scientific Electronic Library Online (SciELO Brazil), Latin American and Caribbean Health Sciences Literature (LILACS) and US National Library of Medicine (MedLine/PubMed) databases using the descriptors antibiotic/antimicrobial, Clostridium difficile/Clostridioides difficile, intestinal microbiota/intestinal microbiome and fecal transplantation. Results Interventions on microbiota include the use of probiotics, prebiotics, and fecal microbiota transplantation as therapeutic methods. Results show that fecal microbiota transplantation is an excellent alternative for the treatment of recurrent C. difficile infections.


2021 ◽  
Vol 10 (3) ◽  
pp. 389
Author(s):  
Eleftheria Kampouri ◽  
Antony Croxatto ◽  
Guy Prod’hom ◽  
Benoit Guery

Clostridioides difficile is an increasingly common pathogen both within and outside the hospital and is responsible for a large clinical spectrum from asymptomatic carriage to complicated infection associated with a high mortality. While diagnostic methods have considerably progressed over the years, the optimal diagnostic algorithm is still debated and there is no single diagnostic test that can be used as a standalone test. More importantly, the heterogeneity in diagnostic practices between centers along with the lack of robust surveillance systems in all countries and an important degree of underdiagnosis due to lack of clinical suspicion in the community, hinder a more accurate evaluation of the burden of disease. Our improved understanding of the physiopathology of CDI has allowed some significant progress in the treatment of CDI, including a broader use of fidaxomicine, the use of fecal microbiota transplantation for multiples recurrences and newer approaches including antibodies, vaccines and new molecules, already developed or in the pipeline. However, the management of CDI recurrences and severe infections remain challenging and the main question remains: how to best target these often expensive treatments to the right population. In this review we discuss current diagnostic approaches, treatment and potential prevention strategies, with a special focus on recent advances in the field as well as areas of uncertainty and unmet needs and how to address them.


Sign in / Sign up

Export Citation Format

Share Document