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 Complete Microbiota Engraftment Is Not Essential for Recovery from Recurrent Clostridium difficile Infection following Fecal Microbiota Transplantation

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Christopher Staley ◽  
Colleen R. Kelly ◽  
Lawrence J. Brandt ◽  
Alexander Khoruts ◽  
Michael J. Sadowsky
Keyword(s):  
Clostridium Difficile ◽  
Bacterial Communities ◽  
Healthy Donor ◽  
Fecal Microbiota Transplantation ◽  
Fecal Microbiota ◽  
Mean Value ◽  
Bile Acid Metabolism ◽  
Secondary Bile Acid ◽  
Stool Samples ◽  
Relative Abundances

ABSTRACT Bacterial communities from subjects treated for recurrent Clostridium difficile infection (rCDI) by fecal microbiota transplantation (FMT), using either heterologous donor stool samples or autologous stool samples, were characterized by Illumina next-generation sequencing. As previously reported, the success of heterologous FMT (90%) was superior to that of autologous FMT (43%) ( P = 0.019), and post-FMT intestinal bacterial communities differed significantly between treatment arms ( P < 0.001). Subjects cured by autologous FMT typically had greater abundances of the Clostridium XIVa clade and Holdemania bacteria prior to treatment, and the relative abundances of these groups increased significantly after FMT compared to heterologous FMT and pre-FMT samples. The typical shift to post-FMT, donor-like assemblages, featuring high relative abundances of genera within the Bacteroidetes and Firmicutes phyla, was not observed in the autologous FMT subjects. Autologous FMT patient bacterial communities were significantly different in composition than those for heterologous FMT patients and donors ( P < 0.001). The SourceTracker program, which employs a Bayesian algorithm to determine source contributions to sink communities, showed that patients initially treated by heterologous FMT had significantly higher percentages of engraftment (i.e., similarity to donor communities, mean value of 74%) compared to those who suffered recurrence following autologous FMT (1%) ( P ≤ 0.013). The findings of this study suggest that complete donor engraftment may be not necessary if functionally critical taxa are present in subjects following antibiotic therapy. IMPORTANCE This study provides a detailed characterization of fecal bacterial communities in subjects who participated in a previously published randomized clinical trial to treat recurrent C. difficile infection (rCDI). Bacterial communities were characterized to determine differences between subjects who received fecal bacteria either from healthy donor stool samples or their own stool samples as “placebo” in order to determine which groups of bacteria were most important in achieving a cure. The results of this study suggested that bacteria associated with secondary bile acid metabolism could potentially provide resistance to infection and that complete transfer of healthy donor microorganisms was not necessary to resolve CDI following unsuccessful antibiotic treatment.

scholarly journals FECAL MICROBIOTES TRANSPLANTATION TECHNOLOGIES: MEDICAL, BIOTECHNOLOGICAL AND REGULATORY ASPECTS

2021 ◽  
Vol 14 (1) ◽  
pp. 46-56
Author(s):  
M. M. Bakalchuk ◽  
Keyword(s):  
Clinical Practice ◽  
Gastrointestinal Tract ◽  
Clostridium Difficile ◽  
Fecal Microbiota Transplantation ◽  
Treatment Method ◽  
Fecal Microbiota ◽  
Medical Community ◽  
Therapeutic Application ◽  
Regulatory Aspects ◽  
Recurrent Clostridium Difficile Infection

Fecal microbiota transplantation (FMT) is a treatment method based on donor's fecal solution injection into the patient's gastrointestinal tract. FMT is effectively used in the treatment of recurrent Clostridium difficile infection. There is also growing interest in the therapeutic application of the method to treat metabolic, autoimmune and other disorders that was not previously associated with intestinal microbiota. Despite the promising results of FMT use, the organizational and legal matters and that of the safety FMT application have not yet been resolved in the European and Ukrainian medical community. The purpose of this review was to summarize information on the FMT application and the regulatory aspects of its use. The analysis of the practical instructions provisions of for FMT applying in clinical practice was carried out, and the bioethical problems associated with the FMT use were investigated.

scholarly journals Gut Microbiota and Type 2 Diabetes Mellitus: Association, Mechanism, and Translational Applications

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Lili Zhang ◽  
Jinjin Chu ◽  
Wenhao Hao ◽  
Jiaojiao Zhang ◽  
Haibo Li ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Short Chain Fatty Acids ◽  
Fecal Microbiota ◽  
Secondary Bile Acid ◽  
Underlying Mechanisms

Gut microbiota has attracted widespread attention due to its crucial role in disease pathophysiology, including type 2 diabetes mellitus (T2DM). Metabolites and bacterial components of gut microbiota affect the initiation and progression of T2DM by regulating inflammation, immunity, and metabolism. Short-chain fatty acids, secondary bile acid, imidazole propionate, branched-chain amino acids, and lipopolysaccharide are the main molecules related to T2DM. Many studies have investigated the role of gut microbiota in T2DM, particularly those butyrate-producing bacteria. Increasing evidence has demonstrated that fecal microbiota transplantation and probiotic capsules are useful strategies in preventing diabetes. In this review, we aim to elucidate the complex association between gut microbiota and T2DM inflammation, metabolism, and immune disorders, the underlying mechanisms, and translational applications of gut microbiota. This review will provide novel insight into developing individualized therapy for T2DM patients based on gut microbiota immunometabolism.

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 Influence of Cultivation pH on Composition, Diversity, and Metabolic Production in an In Vitro Human Intestinal Microbiota

Fermentation ◽  
2021 ◽  
Vol 7 (3) ◽  
pp. 156
Author(s):  
Regina Haindl ◽  
Simon Schick ◽  
Ulrich Kulozik
Keyword(s):  
Cell Count ◽  
Fecal Microbiota Transplantation ◽  
Treatment Method ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Microbial Composition ◽  
Human Intestinal Microbiota ◽  
Special Value ◽  
Health Promoting

Fecal microbiota transplantation, an alternative treatment method for gastrointestinal diseases, has a high recovery rate, but comes with disadvantages, such as high donor requirements and the low storability of stool. A solution to overcome these problems is the cultivation of an in vitro microbiota. However, the influence of cultivation conditions on the pH are yet unknown. In this study, the influence of the cultivation pH (6.0–7.0) on the system’s behavior and characteristics, including cell count, metabolism, and microbial composition, was investigated. With an increasing cultivation pH, an increase in cell count, total amount of SCFAs, acetate, propionate, and the abundance of Bacteroidetes and Verrucomicrobia were observed. For the concentration of butyrate and the abundance of Actinobacteria and Firmicutes, a decrease with increasing pH was determined. For the concentration of isovalerate, the abundance of Proteobacteria and diversity (richness and Shannon effective), no effect of the pH was observed. Health-promoting genera were more abundant at lower pH levels. When cultivating an in vitro microbiota, all investigated pH values created a diverse and stable system. Ultimately, therefore, the choice of pH creates significant differences in the established in vitro microbiota, but no clear recommendations for a special value can be made.

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 Establishment of an In Vitro System of the Human Intestinal Microbiota: Effect of Cultivation Conditions and Influence of Three Donor Stool Samples

2021 ◽  
Vol 9 (5) ◽  
pp. 1049
Author(s):  
Regina Haindl ◽  
Julia Engel ◽  
Ulrich Kulozik
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Stable State ◽  
Short Chain Fatty Acids ◽  
Gastrointestinal Diseases ◽  
Fecal Microbiota ◽  
Short Chain ◽  
Cultivation Conditions ◽  
In Vitro System ◽  
Stool Samples

Fecal microbiota transplantation (FMT) is an alternative method for the treatment of gastrointestinal diseases with a high recovery rate. Disadvantages are ethical concerns, high donor requirements and the low storability of stool samples. The cultivation of an in vitro microbiota in a continuous bioreactor was established as an alternative to FMT to overcome these problems. In this study, the influence of the system parameters and donor stool characteristics was investigated. Each continuous colonic fermentation system was inoculated with feces from three different donors until a stable state was established. The influence of the fermentation conditions on the system’s behavior regarding cell count, metabolic activity, short-chain fatty acid profile and microbiota composition as well as richness and diversity was assessed. Cultivation conditions were found to affect the microbial system: the number of cells and the production of short-chain fatty acids increased. The abundance of Actinobacteria and Firmicutes decreased, Bacteroidetes increased, while Proteobacteria and Verrucomicrobia remained largely unaffected. Diversity in the in vitro system decreased, but richness was unaffected. The cultivation of stool from different donors revealed that the performance of the created in vitro system was similar and comparable, but unique characteristics of the composition of the original stool remained.

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