scholarly journals Applying fecal microbiota transplantation (FMT) to treat recurrent Clostridium difficile infections (rCDI) in children

PeerJ ◽  
2018 ◽  
Vol 6 ◽  
pp. e4663 ◽  
Author(s):  
Shaaz Fareed ◽  
Neha Sarode ◽  
Frank J. Stewart ◽  
Aneeq Malik ◽  
Elham Laghaie ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Adverse Effects ◽  
Gut Microbiome ◽  
Pediatric Patients ◽  
Fecal Microbiota Transplantation ◽  
Diversity Index ◽  
Microbial Community Composition ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Significant Difference

Background Fecal Microbiota Transplantation (FMT) is an innovative means of treating recurrent Clostridium difficile infection (rCDI), through restoration of gut floral balance. However, there is a lack of data concerning the efficacy of FMT and its impact on the gut microbiome among pediatric patients. This study analyzes clinical outcomes and microbial community composition among 15 pediatric patients treated for rCDI via FMT. Methods This is a prospective, observational, pilot study of 15 children ≤18 years, who presented for rCDI and who met inclusion criteria for FMT at a pediatric hospital and pediatric gastroenterology clinic. Past medical history and demographics were recorded at enrollment and subsequent follow-up. Specimens of the donors’ and the patients’ pre-FMT and post-FMT fecal specimen were collected and used to assess microbiome composition via 16S rRNA gene sequencing. Results FMT successfully prevented rCDI episodes for minimum of 3 months post-FMT in all patients, with no major adverse effects. Three patients reported continued GI bleeding; however, all three also had underlying Inflammatory Bowel Disease (IBD). Our analyses confirm a significant difference between pre-and post-FMT gut microbiome profiles (Shannon diversity index), whereas no significant difference was observed between post-FMT and donor microbiome profiles. At the phyla level, post-FMT profiles showed significantly increased levels of Bacteroidetes and significantly decreased levels of Proteobacteria. Subjects with underlying IBD showed no difference in their pre-and post-FMT profiles. Conclusion The low rate of recurrence or re-infection by C. difficile, coupled with minimal adverse effects post-FMT, suggests that FMT is a viable therapeutic means to treat pediatric rCDI. Post-FMT microbiomes are different from pre-FMT microbiomes, and similar to those of healthy donors, suggesting successful establishment of a healthier microbiome.

scholarly journals A Mathematical Model to Evaluate the Routine Use of Fecal Microbiota Transplantation to Prevent Incident and Recurrent Clostridium difficile Infection

2014 ◽  
Vol 35 (1) ◽  
pp. 18-27 ◽  
Author(s):  
Eric T. Lofgren ◽  
Rebekah W. Moehring ◽  
Deverick J. Anderson ◽  
David J. Weber ◽  
Nina H. Fefferman
Keyword(s):  
Mathematical Model ◽  
High Risk ◽  
Clostridium Difficile ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Low Risk ◽  
Billing Data ◽  
Potential Health ◽  
Significant Difference ◽  
Incident Cases

Objective.Fecal microbiota transplantation (FMT) has been suggested as a new treatment to manage Clostridium difficile infection (CDI). With use of a mathematical model of C. difficile within an intensive care unit (ICU), we examined the potential impact of routine FMT.Design, Setting, and Patients.A mathematical model of C. difficile transmission, supplemented with prospective cohort, surveillance, and billing data from hospitals in the southeastern United States.Methods.Cohort, surveillance, and billing data as well as data from the literature were used to construct a compartmental model of CDI within an ICU. Patients were defined as being in 1 of 6 potential health states: uncolonized and at low risk; uncolonized and at high risk; colonized and at low risk; colonized and at high risk; having CDI; or treated with FMT.Results.The use of FMT to treat patients after CDI was associated with a statistically significant reduction in recurrence but not with a reduction in incident cases. Treatment after administration of high-risk medications, such as antibiotics, did not result in a decrease in recurrence but did result in a statistically significant difference in incident cases across treatment groups, although whether this difference was clinically relevant was questionable.Conclusions.Our study is a novel mathematical model that examines the effect of FMT on the prevention of recurrent and incident CDI. The routine use of FMT represents a promising approach to reduce complex recurrent cases, but a reduction in CDI incidence will require the use of other methods to prevent transmission.

scholarly journals Inter-individual Recovery of the Microbiota and Metabolome Over Time Following Fecal Microbiota Transplantation in Patients with RecurrentClostridium difficileInfection

2017 ◽  
Author(s):  
Anna M. Seekatz ◽  
Casey M. Theriot ◽  
Krishna Rao ◽  
Yu-Ming Chang ◽  
Alison E. Freeman ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Fecal Microbiota Transplantation ◽  
Significant Proportion ◽  
Short Chain Fatty Acids ◽  
Treatment Method ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Secondary Bile Acid ◽  
Over Time

ABSTRACTA significant proportion of individuals develop recurrentClostridium difficileinfection (CDI) following initial disease. Fecal microbiota transplantation (FMT), a highly effective treatment method for recurrent CDI, has been demonstrated to induce microbiota recovery, a critical component of disease recovery. However, identification of the specific microbes and their functions that directly impact recovery from CDI remains difficult. We assessed for associations among microbial community members and metabolites in patients with recurrent CDI following treatment with FMT over time to identify groups of bacteria with potential restorative functions. Using 16S rRNA gene-based sequencing, we observed marked similarity of the microbiota between recipients following FMT (n = 6, sampling up to 6 months post-FMT) and their respective donors. Increased levels of the secondary bile acid deoxycholic acid and the short chain fatty acids (SCFAs) butyrate, acetate, and propionate were observed post-FMT. To take into account longitudinal sampling and intra-individual differences, we applied a generalized estimating equation approach to model metabolite concentrations with the presence of specific members of the microbiota. Microbial metabolites that were increased following FMT associated with members classified within theLachnospiraceae, Ruminococcaceae, and unclassifiedClostridialesfamilies. In contrast, members of these taxa were inversely associated with primary bile acids. The longitudinal aspect of this study allowed us to characterize individualized patterns of recovery, revealing variability between and within patients following FMT.IMPORTANCEClostridium difficileinfection (CDI) is an urgent and serious healthcare-associated problem. In recent years, fecal microbiota transplantation (FMT) has been successfully used to treat recurrent CDI, a frequent outcome of disease. While it is apparent that FMT promotes recovery of the microbiota, it is unclear how microbes and their functions promote recovery from disease. This study aimed to identify associations among microbes and metabolites following FMT and to identify critical microbial functions following FMT treatment for recurrent CDI. Overall, recovery of the metabolome was highly dynamic and individualized in all patients, who were all successfully treated. Our results suggest that microbial changes following FMT may be highly specific to the donor-recipient relationship. Further understanding of the host-microbe environments necessary to enable successful transplantation of microbes during FMT could aid development of specific microbial therapeutics for recurrent CDI and other gastrointestinal diseases.

scholarly journals 1497. Relapsing Clostridium difficile Infection: Resolution with Combined Patient Choice Fecal Microbiota Transplantation, Vancomycin Taper, and Vancomycin Suppression

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S545-S545
Author(s):  
Rebecca D Shadowen ◽  
Steven A Edds
Keyword(s):  
Clostridium Difficile ◽  
Clostridium Difficile Infection ◽  
Complete Resolution ◽  
Fecal Microbiota Transplantation ◽  
The United States ◽  
Fecal Microbiota ◽  
Small Sample ◽  
Patient Choice ◽  
Primary Study ◽  
Significant Difference

Abstract Background Clostridium difficile infection (CDI) results in approximately a half a million cases and 15,000 deaths annually in the United States. Relapse rates vary between 20 and 50% and account for frequent readmissions and morbidity. Application of treatment modalities for relapsing cases resulting in complete resolution is reported here. Methods An observational analytical cohort study was done from June 2014 to December 2018 by offering options to patients for treatment of their CDI relapse. Each chose between Fecal Microbiota Transplantation (FMT; N = 52), Vancomycin po 6-week taper (VTa; N = 4), or Vancomycin 125 mg po daily 6-month suppression (VSu; N = 18). The FMT was given either as a liquid NG instillation (FMT-L) twice 12–24 hours apart (N = 47) or 20 capsules (FMT-C) given over 90 minutes (N = 5). Patients were followed for at least 8 weeks after treatment with readmissions tracked for 6 months in all cases. Fisher exact test was used for statistical significance. Results No patient was readmitted to the hospital for CDI-associated problems during the term of this study. More men choose po Vancomycin with more women choosing FMT (VTa/VSu Female 38%: Male 62% and FMT Female 80%: Male 20%; P < 0.01). Overall, initial response rate was 90%. Resolution of CDI was highest among the FMT-L (95.7%; N = 45/47; P = 1) and the VSu (94%; N-17/18; P = 1). The VTa group had 75% resolution (N = 3/4; nsd). The FMT-C arm showed a 40% success rate (N = 2/5; nsd). Treatment failures (N = 7) chose re-treatment with 6 cases repeating VTa having one relapse responding to FMT-L. One relapse in the VSu group responded to a 6 months daily Vancomycin suppressive course. The only statistically significant difference was in male to female ratios. Cost of therapy was highest for FMT-L $2326, FMT-C $1870, VSu $965, and VTa $700 average per course. Conclusion This report integrates options in treatment that follows the relapsing CDI patient to complete resolution. This eliminated hospital readmission and further morbidity. Allowing the patient freedom of treatment option was well received. Of the treatment arms, FMT-L and VSu were equivalent in outcomes, followed by VTa and FMT-C. FMT-L as 2 instillations provides higher response rates than previously reported. This was a small sample size; however, primary study endpoints of no hospitalizations and complete resolution were attained. Disclosures All authors: No reported disclosures.

scholarly journals Durable Long-Term Bacterial Engraftment following Encapsulated Fecal Microbiota Transplantation To Treat Clostridium difficile Infection

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Christopher Staley ◽  
Thomas Kaiser ◽  
Byron P. Vaughn ◽  
Carolyn Graiziger ◽  
Matthew J. Hamilton ◽  
...  
Keyword(s):  
Clostridium Difficile ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Rescue Therapy ◽  
Specific Effect ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Content Type ◽  
Freeze Dried

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.

scholarly journals One dog’s waste is another dog’s wealth: A pilot study of fecal microbiota transplantation in dogs with acute hemorrhagic diarrhea syndrome

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250344
Author(s):  
Arnon Gal ◽  
Patrick C. Barko ◽  
Patrick J. Biggs ◽  
Kristene R. Gedye ◽  
Anne C. Midwinter ◽  
...  
Keyword(s):  
Pilot Study ◽  
Fecal Microbiota Transplantation ◽  
Diversity Index ◽  
Fecal Microbiota ◽  
Rrna Gene ◽  
Post Discharge ◽  
Small Pilot Study ◽  
Clinical Scores ◽  
Healthy Donors ◽  
Diarrhea Syndrome

Canine acute hemorrhagic diarrhea syndrome (AHDS) has been associated in some studies with Clostridioides perfringens overgrowth and toxin-mediated necrosis of the intestinal mucosa. We aimed to determine the effect of a single fecal microbiota transplantation (FMT) on clinical scores and fecal microbiomes of 1 and 7 dogs with AHDS from New Zealand and South Africa. We hypothesized that FMT would improve AHDS clinical scores and increase microbiota alpha-diversity and short-chain fatty acid (SCFA)-producing microbial communities’ abundances in dogs with AHDS after FMT. We sequenced the V3-V4 region of the 16S-rRNA gene in the feces of AHDS FMT-recipients and sham-treated control dogs, and their healthy donors at admission, discharge, and 30 days post-discharge. There were no significant differences in median AHDS clinical scores between FMT-recipients and sham-treated controls at admission or discharge (P = 0.22, P = 0.41). At admission, the Shannon diversity index (SDI) was lower in AHDS dogs than healthy donors (P = 0.002). The SDI did not change from admission to 30 days in sham-treated dogs yet increased in FMT-recipients from admission to discharge (P = 0.04) to levels not different than donors (P = 0.33) but significantly higher than sham-treated controls (P = 0.002). At 30 days, the SDI did not differ between FMT recipients, sham-treated controls, and donors (P = 0.88). Principal coordinate analysis of the Bray-Curtis index separated post-FMT and donor dogs from pre-FMT and sham-treated dogs (P = 0.009) because of increased SCFA-producing genera’s abundances after FMT. A single co-abundance subnetwork contained many of the same OTUs found to be differentially abundant in FMT-recipients, and the abundance of this module was increased in FMT-recipients at discharge and 30 days, compared to sham-treated controls. We conclude in this small pilot study FMT did not have any clinical benefit. A single FMT procedure has the potential to increase bacterial communities of SCFA-producing genera important for intestinal health up to 30 days post-FMT.

scholarly journals The Composition and Predictive Function of the Fecal Microbiota Differ Between Young and Adult Donkeys

2020 ◽  
Vol 11 ◽  
Author(s):  
Jingya Xing ◽  
Guiqin Liu ◽  
Xinzhuang Zhang ◽  
Dongyi Bai ◽  
Jie Yu ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Microbial Community Composition ◽  
Age Groups ◽  
Fecal Microbiota ◽  
Microbial Colonization ◽  
Rrna Gene ◽  
Functional Prediction ◽  
Microbial Composition ◽  
Significant Difference ◽  
And Function

The community of microorganisms inhabiting the gastrointestinal tract of monogastric herbivores played critical roles in the absorption of nutrients and keeping the host healthy. However, its establishment at different age groups has not been quantitatively and functionally examined. The knowledge of microbial colonization and its function in the intestinal tract of different-age donkeys is still limited. By applying the V3–V4 region of the bacterial 16S rRNA gene and functional prediction on fecal samples from different-age donkeys, we characterized the gut microbiota during the different age groups. In contrast to the adult donkeys, the gut microbiota diversity and richness of the young donkeys showed significantly less resemblance. The microbial data showed that diversity and richness increased with age, but a highly individual variation of microbial composition was observed at month 1. Principal coordinate analysis (PCoA) revealed a significant difference across five time points in the feces. The abundance of Bacteroides, Lactobacillus, and Odoribacter tended to decrease, while the proportion of Streptococcus was significantly increased with age. For functional prediction, the relative abundance of pathways had a significant difference in the feces across different age groups, for example, Terpenoids and Polyketides and Folding, Sorting, and Degradation (P &lt; 0.05 or P &lt; 0.01). The analysis of beta diversity (PCoA and LEfSe) and microbial functions predicted with PICRUSt (NSTIs) clearly divided the donkeys into foals (≤3 months old) and adults (≥7 months old). Microbial community composition and structure had distinctive features at each age group, in accordance with functional stability of the microbiota. Our findings established a framework for understanding the composition and function of the fecal microbiota to differ between young and adult donkeys.

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