Microbial Engraftment and Efficacy of Fecal Microbiota Transplant for Clostridium Difficile in Patients With and Without Inflammatory Bowel Disease

Hirten, Robert; Grinspan, Ari; Fu, Shih-Chen; Luo, Yuying; Suárez‐Fariñas, Mayte; Rowland, Jem J.; Contijoch, Eduardo J.; Mogno, Ilaria; Yang, Nancy Y. C.; Luong, Tramy; Labrias, Philippe R; Peter, Inga; Cho, Judy H.; Sands, Bruce E.; Colombel, Jean Fréd́eric; Faith, Jeremiah J.; Clemente, José C.

doi:10.1093/ibd/izy398

Cited by 42 publications

(53 citation statements)

References 32 publications

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“…The absence of complete engraftment is consistent with findings in other disease states such as C. difficile disease and IBD, where there is not complete replacement of the recipient's microbiome with the donor's microbiome, yet clinical benefits and changes in the microbiome with FMT have been observed [ 28 – 30 ]. This suggests that the effects of the microbiome may not be dependent upon a single organism or group of organisms but rather on the functionality of the microbiome.…”

Section: Discussionsupporting

confidence: 80%

Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV

Utay¹,

Monczor²,

Somasunderam³

et al. 2020

PAI

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Background: Reduced 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.Methods: Six 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.Results: Median 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. Alpha diversity increased in 4 participants from weeks 0 to 6, including the 3 with the lowest alpha diversity at week 0. At week 26, alpha 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 alpha diversity that improved between weeks 0 and 6 with a shift in distribution.Conclusions: Weekly FMT was safe and well-tolerated. Alpha diversity increased in participants with the lowest baseline alpha 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

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Section: Discussionsupporting

confidence: 80%

Evaluation of Six Weekly Oral Fecal Microbiota Transplants in People with HIV

Utay¹,

Monczor²,

Somasunderam³

et al. 2020

PAI

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“…Human subjects: All individuals of age 18 and over were recruited in the study using a protocol approved by the Mount Sinai Institutional Review Board (HS# 11-01669). The donors and patients who received FMT for rCDI or rCDI and IBD were described in a previous study analyzed with 16S rRNA amplicon sequencing 69 .…”

Section: Methodsmentioning

confidence: 99%

Quantification of discrete gut bacterial strains following fecal transplantation for recurrentClostridioides difficileinfection demonstrates long-term stable engraftment in non-relapsing recipients

Aggarwala

Mogno

et al. 2020

Preprint

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Fecal Microbiota Transplantation (FMT), while successful for the treatment of recurrent Clostridioides difficile (rCDI) infection, lacks a quantitative identification of the discrete bacterial strains that transmit and stably engraft in recipients, and their association with clinical outcomes. Using >1,000 unique bacterial strains isolated and sequenced from a combination of 22 FMT donors and recipients, we develop a statistical approach Strainer to detect and track sequenced bacterial strains from low depth metagenomic sequencing data. On application to 14 FMT interventions, we detect stable and high engraftment of ∼71% of gut microbiota strains in recipients at even 5-years post-transplant, a remarkably durable therapeutic from a single administration. We found differential transmission and engraftment efficacy across bacterial taxonomic groups over short and long-time scales. Although ∼80% of the original pre-FMT recipient strains were eliminated by the FMT, those strains that remain persist even 5 years later, along with newer strains acquired from the environment. The precise quantification of donor bacterial strains in recipients independently explained the clinical outcomes of early and late relapse. Our framework identifies the consistently engrafting discrete bacterial strains for use in Live Biotherapeutic Products (LBP) as a safer, scalable alternative to FMT and enables systematic evaluation of different FMT and LBP study designs.

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“…Finally, a unique risk to the IBD population is the risk for flare of underlying IBD, which in one study was reported to be as high as 25.6% in IBD patients receiving FMT for recurrent CDI [ 36 ]. Nevertheless, a different study examining FMT in IBD patients with recurrent CDI reported no serious AEs [ 44 ]. A Cochrane meta-analysis examining FMT as a treatment for IBD included an analysis of 277 patients for serious AEs, indicating that 10/140 (7%) who received FMT experienced a serious AE compared to 7/137 (5%) in the control group (RR 1.40, 95% CI 0.55–3.58, I2 = 0%) [ 45 ].…”

Section: Case Discussionmentioning

confidence: 99%