Successful treatment of fulminant <i>Clostridioides difficile</i> infection with emergent fecal microbiota transplantation in a patient with acute myeloid leukemia and prolonged, severe neutropenia

Lee, Matthew S L; Ramakrishna, Bharat; Moss, Alan C.; Gold, Howard S.; Branch‐Elliman, Westyn

doi:10.1111/tid.13216

Cited by 15 publications

(11 citation statements)

References 20 publications

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“…Helicobacter pylori has been classified as a carcinogen since 1994, although gastric cancer appears in the gastric mucosa epithelium, several observations suggest that the cancer cells may originate from circulating bone marrow stem cells recruited to the mucosa to replace normal gastric stem cells that have underwent apoptosis due to Helicobacter pylori infection [29]. Matthwe S. L. Lee et al reported that a patient with AML and prolonged severe neutropenia was successfully treated with emergent fecal microbiota transplantation (FMT) due to Clostridioides difficile infection [31]. Kazuhiko Kakihana et al indicated that FMT might shift the systemic allogeneic immune response to an anti-inflammatory state by changing the intestinal microbiota and might be effective against other forms of acute graft-versus-host disease [32], all of which suggested that FMT might be a promising and safe therapy.…”

Section: Discussionmentioning

confidence: 99%

Profiling of gut microbial dysbiosis in adults with myeloid leukemia

et al. 2021

FEBS Open Bio

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Dysregulation of gut microbiota is implicated in the pathogenesis of various diseases, including metabolic diseases, inflammatory diseases, and cancer. To date, the link between gut microbiota and myeloid leukemia (ML) remains largely unelucidated. Herein, a total of 29 patients with acute myeloid leukemia (AML), 17 patients with chronic myeloid leukemia (CML), and 33 healthy subjects were enrolled, and gut microbiota were profiled via Illumina sequencing of the 16S rRNA. We evaluated the correlation between ML and gut microbiota. The microbial α-diversity and β-diversity exhibited significant differences between ML patients and healthy controls (HCs). Compared to healthy subjects, we found that at the phylum level, the relative abundance of Actinobacteria, Acidobacteria, and Chloroflexi were increased, while that of Tenericutes was decreased. Correspondingly, at the genus level in ML, Streptococcus were increased, especially in AML patients, while Megamonas (p=0.02), Lachnospiraceae NC2004 group, and Prevotella 9 (p=0.007) were decreased. Moreover, ML-enriched species, including Sphingomonas, Lysobacyer, Helicobacter, Lactobacillus, Enterococcus, and Clostridium sensu stricto 1, were identified. Our results indicate that the gut microbiota was altered in ML patients compared to that of healthy subjects, which could

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Section: Discussionmentioning

confidence: 99%

Profiling of gut microbial dysbiosis in adults with myeloid leukemia

et al. 2021

FEBS Open Bio

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“…AFMT treatment was considered to limit the risk of such complications by promoting a return to non-disturbed intestinal microbiota. Nevertheless, there is limited clinical evidence to date on FMT e ciency in patients suffering from ALM and treated with antibiotics [37].…”

Section: Discussionmentioning

confidence: 99%

An oral FMT capsule as efficient as an enema for microbiota reconstruction following disruption by antibiotics, as assessed in an in vitro human gut model.

Verdier

Denis

Cyrielle³

et al. 2020

Preprint

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Abstract Background Fecal microbiota transfer (FMT) is an innovative treatment already successfully used in recurrent Clostridioides difficile infections. Researchers and clinicians are exploring its potential for treating other digestive or extra-intestinal pathologies where gut microbial dysbiosis has been evidenced, such as inflammatory bowel disease, obesity or cancers. Oral capsules were recently developed to address gaps of traditional routes of FMT such as enema or colonoscopy. Clinical studies are obviously the gold standard to evaluate FMT efficiency but remain limited by regulatory, ethics and cost constraints. The aim of the study was to use the in vitro human Artificial Colon ARCOL to compare the efficiency of two enema dosage (10 and 30 g) and a new oral caecum-release capsule in restoring gut microbiota composition and activity after treatment with ciprofloxacin, an antibiotic used in leukemia patients. Results By integrating the main physicochemical parameters of the human colon (pH, retention time, nutrient supply and anaerobiosis), ARCOL was shown to capture microbial diversity and inter-individual variability of stools from three healthy donors. Treatment with ciprofloxacin led to a state of marked dysbiosis with a sharp decrease in fermentation activities (production of gases and short chain fatty acids), a loss of microbial diversity and a shift in bacterial populations. All FMT treatments were able to speed-up the restoration of microbial profiles and functions, by decreasing the number of dysbiotic days from 12 to 7–8 depending on the FMT modes. Of note, the bacterial load showed no major influence on enema performance, and oral capsule was almost as efficient as enema even if the amount of administered bacteria was 100 times lower. Conclusions This study provides the first example of using an in vitro human colon model for evaluating autologous FMT efficiency and highlights the potential of oral capsule compared to a traditional enema formulation. This new mode of FMT administration combines efficiency with convenient and minimally invasive mode of administration. In accordance to 3R rules, gut models like ARCOL can be advantageously used to test FMT in preclinical phases as an alternative to in vivo assays.

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“…In immunocompromised hosts, safety issues, especially disseminated bacterial infections in neutropenic hosts, are of concern. To date, data on efficacy and safety of FMT for rCDI in haematologic malignancy and HSCT are limited to small case series and case reports [100][101][102][103][104][105]. A case report that led to an FDA national alert and mandated additional screening for those conducting FMT research under FDA supervision described a patient in a trial of FMT after allogenic HSCT (NCT03720392), who died from severe neutropenic sepsis secondary extended-spectrum beta-lactamase (ESBL) E. coli.…”

Section: Primary and Secondary Prevention Methodsmentioning

confidence: 99%