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

AbstractAcute 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.

Download Full-text

Gut microbiota profiles of treatment-naïve adult acute myeloid leukemia patients with neutropenic fever during intensive chemotherapy

10.1101/2020.07.09.194910 ◽

2020 ◽

Author(s):

Thanawat Rattanathammethee ◽

Pimchanok Tuitemwong ◽

Parameth Thiennimitr ◽

Phinitphong Sarichai ◽

Sarisa Na Pombejra ◽

...

Keyword(s):

Bone Marrow ◽

Acute Myeloid Leukemia ◽

Febrile Neutropenia ◽

Gut Microbiota ◽

Myeloid Leukemia ◽

Diversity Index ◽

Neutropenic Fever ◽

Intensive Chemotherapy ◽

Treatment Naïve ◽

Acute Myeloid

AbstractIntestinal bacterial flora of febrile neutropenic patients had significantly diverse. However, there were scanty reports of microbiota alteration of adult patients with acute myeloid leukemia (AML). Stool samples of each treatment-naïve AML patient were collected at the day before induction chemotherapy initiation (pretreatment), first day of neutropenic fever and first day of bone marrow recovery. Bacterial DNA was extracted from stool and sequenced bacterial 16s ribosomal RNA genes by next-generation sequencing. Relative abundance, overall richness, Shannon’s diversity index and Simpson’s diversity index were calculated. Ten cases of AML patients (4 men and 6 women) were included with median age of 39 years (range: 19-49) and all of patients developed febrile neutropenia. Firmicutes were dominated over the period of neutropenic fever and subsequent declined after bone marrow recovery contrast to Bacteroidetes and Proteobacteria. Enterococcus was more abundant at febrile neutropenia period compared to pretreatment while Bacteroides and Escherichia was notably declined during the febrile neutropenia. At the operational taxonomic units (OTUs) level, there was significant higher level of overall richness of pretreatment period than febrile neutropenic episode. Both of the diversity indexes of Shannon and Simpson were considerably decreased at febrile neutropenic period. Adult AML patients with first episode of febrile neutropenia after initial intensive chemotherapy demonstrated the significant decrease of gut microbiota diversity and the level of diversity consistently remained constant despite of bone marrow recovery.

Download Full-text