Gut microbiota diversity after autologous fecal microbiota transfer in acute myeloid leukemia patients

Abstract

Acute myeloid leukemia (AML) intensive chemotherapy combined with broad-spectrum antibiotics, leads to gut microbiota dysbiosis promoting pathological conditions and an increased incidence of complications. Here we report findings from a phase II single-arm, multicenter study evaluating autologous fecal microbiota transfer (AFMT) in 25 AML patients treated with intensive chemotherapy and antibiotics (ClinicalTrials.gov number: NCT02928523). The co-primary outcomes of the study are to evaluate the efficacy of AFMT in dysbiosis correction and multidrug-resistant bacteria eradication. The main secondary outcomes are to define a dysbiosis biosignature, to evaluate the effect of dysbiosis correction on patient clinical status, to assess the short and mid-term safety of AFMT in this immunocompromised population, and to evaluate the feasibility of the AFMT procedure and acceptability by the patient. Intensive induction chemotherapy induces a dramatic decrease of α-diversity indices, and a microbial dysbiosis with a significant shift of the microbial communities and domination of pro-inflammatory families. After AFMT treatment, α-diversity indices return to their initial mean levels and the similarity index shows the restoration of microbial communities. The trial meets pre-specified endpoints. AFMT appears to be safe and may be effective for gut microbiota restoration in AML patients receiving intensive chemotherapy and antibiotics, with an excellent gut microbiota reconstruction based on both richness and diversity indices at the species level.

Immunity in acute myeloid leukemia: Where the immune response and targeted therapy meet

“…A clinical study using fecal material transfer (FMT) for ameliorating infection‐based complexities in AML patients undergoing intensive chemotherapy is currently underway (ClinicalTrials.gov Identifier: NCT02928523). A recent report from this study showed that autologous FMT was safe and able to restore the diversity of the microbiome of the patients treated [35] (Table 1), although the full impact of this restoration on patients’ susceptibility to infections was not fully addressed.…”

Fecal Microbiota Transplantation as New Therapeutic Avenue for Human Diseases

“…First, the authors confirmed that in their patients’ sample, chemotherapy-induced a decrease in gut microbiota alpha diversity and an increase in proinflammatory strains. After autologous FMT, alpha diversity returned to initial mean levels and microflora composition showed similarity indicating a restoration in its composition [ 173 ]. Whether autologous FMT might ameliorate AML condition still has to be investigated, but the clinical trial showed that the treatment is safe and reconstructs microbiota richness and diversity.…”

Fixing Functional GI Disorders Using Microbes: Easier Said Than Done

“…From a safety and “ecological restoration potential” perspective this would ideally be the autologous microbiome derived from fecal samples collected from a symbiotic state, prior to the occurrence of the FGID. To this end, acute myeloid leukemia patients treated with chemotherapy combined with a broad-spectrum antibiotic regime typically suffer from gut microbiota dysbiosis but displayed restored microbial communities in a one-armed phase II clinical trial after autologous FMT ( 26 ). Obviously FGID cannot be predicted to occur in the near future in most situations other than scheduled antibiotic treatment.…”