Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation

Murthy, Hemant S.; Gharaibeh, Raad Z.; Al‐Mansour, Zeina; Kozlov, Andrew; Trikha, Gaurav; Newsome, Rachel C.; Gauthier, Josée; Farhadfar, Nosha; Wu, Yu; Kelly, Debra Lynch; Lybarger, John; Jobin, Christian; Wang, Gary P.; Wingard, John R.

doi:10.1016/j.bbmt.2020.07.023

Cited by 11 publications

(6 citation statements)

References 43 publications

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“…63 Second, FMT was essential for the recovery of Collinsella. Collinsella depletion has been associated with neutropenic fever after HCT 64 and microscopic colitis. 65 This genus elicits systemic immunoglobulin responses in inflammatory bowel disease 66 and has been associated with response to FMT in patients with ulcerative colitis.…”

Section: Discussionmentioning

confidence: 99%

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Rashidi

Ebadi

Rehman

et al. 2023

JCO

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PURPOSE Gut microbiota injury in allogeneic hematopoietic cell transplantation (HCT) recipients and patients with AML has been associated with adverse clinical outcomes. Previous studies in these patients have shown improvements in various microbiome indices after fecal microbiota transplantation (FMT). However, whether microbiome improvements translate into improved clinical outcomes remains unclear. We examined this question in a randomized, double-blind, placebo-controlled phase II trial. METHODS Two independent cohorts of allogeneic HCT recipients and patients with AML receiving induction chemotherapy were randomly assigned in a 2:1 ratio to receive standardized oral encapsulated FMT versus placebo upon neutrophil recovery. After each course of antibacterial antibiotics, patients received a study treatment. Up to three treatments were administered within 3 months. The primary end point was 4-month all-cause infection rate. Patients were followed for 9 months. RESULTS In the HCT cohort (74 patients), 4-month infection density was 0.74 and 0.91 events per 100 patient-days in FMT and placebo arms, respectively (infection rate ratio, 0.83; 95% CI, 0.48 to 1.42; P = .49). In the AML cohort (26 patients), 4-month infection density was 0.93 in the FMT arm and 1.25 in the placebo arm, with an infection rate ratio of 0.74 (95% CI, 0.32 to 1.71; P = .48). Unique donor bacterial sequences comprised 25%-30% of the fecal microbiota after FMT. FMT improved postantibiotic recovery of microbiota diversity, restored several depleted obligate anaerobic commensals, and reduced the abundance of expanded genera Enterococcus, Streptococcus, Veillonella, and Dialister. CONCLUSION In allogeneic HCT recipients and patients with AML, third-party FMT was safe and ameliorated intestinal dysbiosis, but did not decrease infections. Novel findings from this trial will inform future development of FMT trials.

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Section: Discussionmentioning

confidence: 99%

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Rashidi

Ebadi

Rehman

et al. 2023

JCO

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“…However, some research indicates that A. muciniphila could be harmful, especially in instances of graft-versus-host disease following allo-HSCT (26) or intestinal inflammation induced by Salmonella enterica Typhimurium (27). Patients who have compromised immune systems are particularly vulnerable to Bacteroides fragilis, a notorious opportunistic pathogen (28,29). All things considered, this begs the question of whether bacterial therapy could be harmful, depending on the pathology and host environment.…”

Section: Discussionmentioning

confidence: 99%

“…Every human has roughly 23,000 genes, but every microbe has about 600,000 genes. Accordingly, fewer than 4% of the entire hologenome is made up of human material (21,29). This review aims to provide a current understanding of the human gut microbiome, as well as an explanation of the shift from symbiosis to dysbiosis and how it affects human health.…”

Section: "Microbiome Dynamics: Symbiosis To Dysbiosis"mentioning

confidence: 99%

From Microbes to Immunity: A Comprehensive Review of Microbiome Modulation

Shahid,

Fatima,

Khan

et al. 2023

JHRR

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The host environment and the native microbial population, or microbiota, make up the microbiome, which is changing how medical professionals see pathogens in connection to human disease and health. The discovery that the majority of bacteria in human bodies perform ecosystem-critical tasks that benefit the entire microbial host system is perhaps the most fundamental development. The microbiome is the broad term for the diverse and abundant population of bacteria found in the gastrointestinal system. This ecosystem contains billions of microbial cells, the majority of which are essential to the preservation of human health. Nutrient consumption, immunology, digestion, and metabolism have all been related to the microbiome. Scientific research has recently established a correlation between alterations in the microbiome and the development of cancer, obesity, inflammatory pulmonary disease, and cardiovascular complications. Epithelial-intestinal microbiome modifications have a substantial impact on the development of diseases and human health. Numerous factors contribute to these changes, such as underlying medical issues and lifestyle decisions. Depending on where in the body it occurs, dysbiosis increases an organism's susceptibility to various threats. Due to the inherent diversity of the human microbiota, these bacteria carry out specific metabolic tasks and play unique roles in each anatomical location. It follows that knowledge of the microbial makeup and activities of the human microbiome in connection to health and disease is essential.

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“…However, whether intestinal commensal bacteria could have a role in the genesis and course of FN has not yet been addressed. In transplanted adults, GM profiles have been observed to diverge between patients who developed FN and those who did not [19]. In particular, patients with FN showed enrichment in Mogibacterium, Bacteroides fragilis and Parabacteroides distasonis, while they showed a depletion in Prevotella, Ruminococcus, Dorea, Blautia and Collinsella.…”

Section: Introductionmentioning

confidence: 99%

Febrile Neutropenia Duration Is Associated with the Severity of Gut Microbiota Dysbiosis in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

Masetti

D’Amico

Zama

et al. 2022

Cancers

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Febrile neutropenia (FN) is a common complication in pediatric patients receiving allogeneic hematopoietic stem cell transplantation (HSCT). Frequently, a precise cause cannot be identified, and many factors can contribute to its genesis. Gut microbiota (GM) has been recently linked to many transplant-related complications, and may also play a role in the pathogenesis of FN. Here, we conducted a longitudinal study in pediatric patients receiving HSCT from three centers in Europe profiling their GM during the transplant course, particularly at FN onset. We found that a more stable GM configuration over time is associated with a shorter duration of fever. Moreover, patients with longer lasting fever exhibited higher pre-HSCT levels of Collinsella, Megasphaera, Prevotella and Roseburia and increased proportions of Eggerthella and Akkermansia at the engraftment. These results suggest a possible association of the GM with the genesis and course of FN. Data seem consistent with previous reports on the relationship of a so-called “healthy” GM and the reduction of transplant complications. To our knowledge, this is the first report in the pediatric HSCT setting. Future studies are warranted to define the underling biological mechanisms and possible clinical implications.

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Baseline Gut Microbiota Composition Is Associated with Major Infections Early after Hematopoietic Cell Transplantation

Cited by 11 publications

References 43 publications

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

Randomized Double-Blind Phase II Trial of Fecal Microbiota Transplantation Versus Placebo in Allogeneic Hematopoietic Cell Transplantation and AML

From Microbes to Immunity: A Comprehensive Review of Microbiome Modulation

Febrile Neutropenia Duration Is Associated with the Severity of Gut Microbiota Dysbiosis in Pediatric Allogeneic Hematopoietic Stem Cell Transplantation Recipients

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