Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis

Eshel, Adi; Sharon, Itai; Nagler, Arnon; Bomze, David; Danylesko, Ivetta; Fein, Joshua; Geva, Mika; Henig, Israel; Shimoni, Avichai; Zuckerman, Tsila; Youngster, Ilan; Koren, Omry

doi:10.1182/bloodadvances.2021005110

Cited by 10 publications

(9 citation statements)

References 23 publications

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“…FMT did not result in BSI, similar to a recent report. 71 Strict donor and product evaluation was key in this safety and should continue in future studies.…”

Section: Discussionmentioning

confidence: 99%

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Rashidi

Ebadi

Rehman

et al. 2023

JCO

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PURPOSE Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial. METHODS Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months. RESULTS In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister. CONCLUSION In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.

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“…FMT did not result in BSI, similar to a recent report. 71 Strict donor and product evaluation was key in this safety and should continue in future studies.…”

Section: Discussionmentioning

confidence: 99%

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Rashidi

Ebadi

Rehman

et al. 2023

JCO

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“…The theoretical benefits of such studies include limiting the toxicity of corticosteroids and creating an opportunity to better elucidate the biological effect of targeted monotherapy. 58 In BMT CTN 1501, sirolimus demonstrated similar treatment efficacy and overall lower toxicity profile as compared to prednisone for standard risk GVHD, defined by the Minnesota GVHD Risk Score and MAGIC biomarker status. 61 There are currently 2 clinical trials investigating this approach in chronic GVHD: ibrutinib as monotherapy (NCT04294641) and the combination of itacitinib and ECP (NCT04446182).…”

Section: Future Directionsmentioning

confidence: 98%

“… 55 , 56 Although infection transmission is a possible risk with FMT, 57 these events are likely rare. 58 Larger multicenter studies are ongoing and planned to better evaluate the clinical efficacy of this microbiome-targeted approaches for SR acute GVHD (NCT03359980, NCT04769895).…”

Section: Future Directionsmentioning

confidence: 99%

Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease

2022

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Graft-versus-host disease (GVHD) is a common complication of allogeneic hematopoietic cell transplantation (HCT) and is associated with significant morbidity and mortality. For many years, there have been few effective treatment options for patients with GVHD. First-line systemic treatment remains corticosteroids, but up to 50% of patients will develop steroid-refractory GVHD and the prognosis for these patients is poor. Elucidation of the pathophysiological mechanisms of acute and chronic GVHD has laid a foundation for novel therapeutic approaches. Since 2017, there have now been 4 approvals by the US Food and Drug Administration (FDA) for GVHD. Ruxolitinib, an oral selective JAK1/2 inhibitor, received FDA approval for the treatment of steroid-refractory acute GVHD in 2019 and remains the only agent approved for acute GVHD. There are currently 3 FDA approvals for the treatment of chronic GVHD: (1) ibrutinib, a BTK inhibitor traditionally used for B-cell malignancies, was the first agent approved for chronic GVHD after failure of one or more lines of systemic therapy, (2) belumosudil, an oral selective inhibitor of ROCK2, for patients with chronic GVHD who received at least 2 prior lines of treatment, and (3) ruxolitinib for chronic GVHD after failure of one or two lines of systemic therapy. In this review, we highlight the clinical data which support these FDA approvals in acute and chronic GVHD with a focus on mechanism of actions, clinical efficacy, and toxicities associated with these agents.

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“…The main problem with existing donor transplants, which are not auto transplants, is that faeces are, by nature, non-sterile, and the transfer of faecal matter from one individual to the next can have unwanted side-effects if not screened properly. This problem can be solved via bacterial cocktails and personalized probiotics, in which we generate the transplant from scratch [80,81,82]. However, to our knowledge, generating from scratch a high variety of taxa has not been done yet commercially.…”

Section: Discussionmentioning

confidence: 99%

Recipient independent high accuracy FMT prediction and optimization in mice and humans

Shtossel

Turjeman

Riumin

et al. 2022

Preprint

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Background Some microbiome composition can be associated with negative outcomes, including among others, obesity, disease and the failure to respond to treatment. Microbiota manipulation or supplementation have been argued to restore the microbiome associated with a healthy condition. Fecal Microbiota Transplantation (FMT) is among the most popular microbiome intervention procedures. Current practices are to choose the transplanted microbiome based on the donor phenotype, and not based on the expected recipient phenotype. However, the two differ drastically. We here propose an algorithm to predict the expected outcome of FMT from the donor phenotype, and optimize the FMT for different required outcomes. Results We here show, using multiple microbiome properties, that the donor and recipient phenotypes differ widely, and propose a tool to predict the recipient phenotype after the FMT using only the donors' microbiome and when available demographics for transplants from humans to either antibiotic treated mice, or other humans. We then extend the method to optimize the best-planned transplant (bacterial cocktails) by combining the predictor and a genetic algorithm (GA). We validate the predictor using a de-novo FMT experiment highlighting the possibility to choose transplants that optimize an array of required goals. We further show that a limited number of taxa is enough to produce an optimal FMT. Conclusions Over the shelf FMT require recipient independent optimized FMT selection. Such a transplant can be from an optimal donor, or from a cultured set of microbes. We have here shown the feasibility of both types of donations in antibiotic treated mice and for transplants between humans.

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Origins of bloodstream infections following fecal microbiota transplantation: a strain-level analysis

Cited by 10 publications

References 23 publications

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Recent FDA Approvals in the Treatment of Graft-Versus-Host Disease

Recipient independent high accuracy FMT prediction and optimization in mice and humans

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