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

**Authors:** Florent Malard, Anne Vekhoff, Simona Lapusan, Francoise Isnard, Evelyne D’incan-Corda, Jérôme Rey, Colombe Saillard, Xavier Thomas, Sophie Ducastelle-Lepretre, Etienne Paubelle, Marie-Virginie Larcher, Clément Rocher, Christian Recher, Suzanne Tavitian, Sarah Bertoli, Anne-Sophie Michallet, Lila Gilis, Pierre Peterlin, Patrice Chevallier, Stéphanie Nguyen, Emilie Plantamura, Lilia Boucinha, Cyrielle Gasc, Mauricette Michallet, Joel Dore, Ollivier Legrand, Mohamad Mohty

PMC · DOI: 10.1038/s41467-021-23376-6 · 2021-05-25

## TL;DR

This study shows that autologous fecal microbiota transfer can safely restore gut microbiota diversity in AML patients undergoing intensive chemotherapy and antibiotics.

## Contribution

The study demonstrates the efficacy and safety of autologous fecal microbiota transfer in restoring gut microbiota in immunocompromised AML patients.

## Key findings

- AFMT restored gut microbiota diversity to pre-chemotherapy levels.
- AFMT was safe and feasible in immunocompromised AML patients.
- Microbial communities showed significant restoration after AFMT treatment.

## 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.

The combination of chemotherapy and broad-spectrum antibiotics induces gut microbiota (GM) dysbiosis in acute myeloid leukaemia (AML) leading to additional complications. Here, the authors report the efficacy in GM restoration and safety of autologous faecal microbiota transfer in treated AML patients in a phase II clinical trial.

## Linked entities

- **Diseases:** acute myeloid leukemia (MONDO:0015667), AML (MONDO:0018874)

## Full-text entities

- **Genes:** IFNG (interferon gamma) [NCBI Gene 3458] {aka IFG, IFI, IMD69}, TGFB2 (transforming growth factor beta 2) [NCBI Gene 7042] {aka CAEND2, G-TSF, LDS4, TGF-beta2}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, CD14 (CD14 molecule) [NCBI Gene 929], FLT3 (fms related receptor tyrosine kinase 3) [NCBI Gene 2322] {aka CD135, FLK-2, FLK2, STK1}, NPM1 (nucleophosmin 1) [NCBI Gene 4869] {aka B23, NPM}
- **Diseases:** anxiety (MESH:D001007), CMV disease (MESH:D003586), depression (MESH:D003866), hematochezia (MESH:D006471), blood cancer (MESH:D019337), bloodstream infections (MESH:D018805), anal fistula (MESH:D012003), irritable bowel syndrome (MESH:D043183), Cancer (MESH:D009369), AFMT (MESH:D005242), acute promyelocytic leukemia (MESH:D015473), diabetes (MESH:D003920), weight increase (MESH:D015431), digestive disorders (MESH:D004066), acute myeloid leukaemia (MESH:D054218), SAEs (MESH:D064420), death (MESH:D003643), AML (MESH:D015470), mucositis (MESH:D052016), thromboembolic (MESH:D013923), gastrointestinal symptoms (MESH:D012817), hemorrhoids (MESH:D006484), multiorgan failure (MESH:D051437), abdominal pain (MESH:D015746), colitis (MESH:D003092), MDRB (MESH:D018088), IC (MESH:D000084202), Leukemia (MESH:D007938), aplasia (MESH:C536482), Inflammatory (MESH:D007249), obesity (MESH:D009765), myelodysplastic syndrome (MESH:D009190), acute (MESH:D000208), fever (MESH:D005334), OL (MESH:C564538), febrile neutropenia (MESH:D064147), extended-spectrum beta-lactamase (MESH:C579922), CDI (MESH:D007239), dysbiosis (MESH:D064806), pain/discomfort (MESH:D010146), GM (MESH:C536735), infectious (MESH:D003141), inflammatory bowel disease (MESH:D015212), diarrhea (MESH:D003967), gastrointestinal GVHD (MESH:D005767), GvHD (MESH:D006086), cardiometabolic diseases (MESH:D024821),  (MESH:D007951)
- **Chemicals:** methicillin (MESH:D008712), Neopterin (MESH:D019798), imipenem-cilastatin (MESH:D000077728), -tazobactam (MESH:D000078142), AFMT (-), Cytarabine (MESH:D003561), PI (MESH:D010716), Cefepim (MESH:D000077723), SYTO9 (MESH:C103389), meronem (MESH:D000077731), IMP (MESH:D007291), propidium iodide (MESH:D011419), anthracycline (MESH:D018943), carbapenems (MESH:D015780), glycopeptide (MESH:D006020), gemtuzumab ozogamicin (MESH:D000079982), butyrate (MESH:D002087), vancomycin (MESH:D014640), Sb (MESH:D000965), piperacillin-tazobactam (MESH:D000077725),  (MESH:D000900)
- **Species:** Yersinia sp. (in: enterobacteria) (species) [taxon 41315], Cryptosporidium sp. (species) [taxon 90962], Vibrio sp. (species) [taxon 678], Bacteria Latreille et al. 1825 (Bacteria stick insect, genus) [taxon 629395], Bifidobacterium (genus) [taxon 1678], Entamoeba histolytica (species) [taxon 5759], Homo sapiens (human, species) [taxon 9606], Microsporidia (microsporidians, phylum) [taxon 6029], Strongyloides stercoralis (species) [taxon 6248], Dientamoeba fragilis (species) [taxon 43352], Rotavirus (genus) [taxon 10912], Enterobacteriaceae (enterobacteria, family) [taxon 543], Giardia duodenalis (species) [taxon 5741], Isospora sp. (species) [taxon 1743397], Roseburia (genus) [taxon 841], Blastocystis hominis (species) [taxon 12968], Clostridium (genus) [taxon 1485], Listeria sp. (species) [taxon 1960103], Escherichia coli (E. coli, species) [taxon 562], Clostridioides difficile (species) [taxon 1496], Cyclospora sp. (species) [taxon 44418], Campylobacter (genus) [taxon 194], Staphylococcus aureus (species) [taxon 1280], Enterococcus (genus) [taxon 1350]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8149453/full.md

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Source: https://tomesphere.com/paper/PMC8149453