Pediatric Fecal Microbiota Transplantation in Recurrent
            <i>Clostridioides Difficile</i>

Parnell, Jacob M; Nicholson, Maribeth R; Kellermayer, Richárd; Kahn, Stacy A.

doi:10.3928/19382359-20211111-01

Cited by 3 publications

(1 citation statement)

References 57 publications

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“…Here an entire community of bacteria and viruses, including metabolites and other fecal particles, are transferred from a healthy donor to a patient to stabilize the GM community. This is used to treat recurrent Clostridioides di cile infection (rCDI) in adults and children with very high cure rates [24,25]. Recently, a small trial investigated maternal FMT in seven cesarean-born babies and found no adverse effects and an infant GM closer resembling infants born vaginally [26].…”

Section: Introductionmentioning

confidence: 99%

Fecal virome is sufficient to reduce necrotizing enterocolitis

Offersen,

Mao,

Spiegelhauer

et al. 2024

Preprint

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Background: Fecal filtrate transfer (FFT, i.e. “sterile filtered” fecal matter) is gaining increasing attention as a safer alternative to traditional fecal microbiota transplantation (FMT) for treating gastrointestinal (GI) complications. Indeed, in the case of necrotizing enterocolitis (NEC), a life-threatening GI emergency occurring in preterm infants, FFT is superior to FMT in terms of both safety and efficacy when investigated in preterm piglets. Since fecal filtrate is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects by modulating the recipient gut microbiota. However, this assumption remains unproven. Results: To address this gap, we isolated the virome of donor feces from the residual postbiotic fluid with no loss of bacteriophage infective potential or bacteriophage spillover to the residual fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring to NEC-susceptible preterm piglets. Importantly, transfer of isolated donor virome was equally effective as FFT in reducing the severity of NEC-like pathology, whereas the residual postbiotic fraction was ineffective. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens. A viral metagenomics analysis indicated enrichment and diversification of recipient gut viral communities with concomitant constraining effect on bacterial composition in accordance with lytic phage predation of resident bacteria. Surprisingly, virome transfer but not residual postbiotic fluid was associated with suspected viral gastroenteritis as indicated by diarrhea, intestinal atrophy, and weight loss. Although virome sequencing did not reveal any obvious causative agent, we suggest that unidentified eukaryotic viruses are candidates responsible for these side effects. Conclusion: Using NEC as a relevant case for microbiota-directed therapy, we show that transfer of isolated fecal virome is sufficient to reduce pathogenic bacterial load and overall disease burden. However, we also highlight that receiving exogenous virome increases the risk of enteric virus infection. Despite diarrhea being a minor concern in the human infant context, future work should identify ways of eliminating eukaryotic viruses without losing treatment efficacy.

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Section: Introductionmentioning

confidence: 99%

Fecal virome is sufficient to reduce necrotizing enterocolitis

Offersen,

Mao,

Spiegelhauer

et al. 2024

Preprint

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Precision medicine: Overview and challenges to clinical implementation

Haga¹

2023

Principles of Gender-Specific Medicine

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Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis

Offersen,

Mao,

Spiegelhauer

et al. 2024

Gut Microbes

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Fecal filtrate transfer (FFT) is emerging as a safer alternative to traditional fecal microbiota transplantation (FMT) – particularly in the context of necrotizing enterocolitis (NEC), a severe gastrointestinal condition affecting preterm infants. Using a preterm piglet model, FFT has demonstrated superiority over FMT in safety and NEC prevention. Since FFT is virtually devoid of bacteria, prokaryotic viruses (bacteriophages) are assumed to mediate the beneficial effects. However, this assumption remains unproven. To address this gap, we separated virus-like particles (30 kDa to 0.45 µm) of donor feces from the residual postbiotic fluid. We then compared clinical and gut microbiota responses to these fractions with the parent FFT solution after transferring them to NEC-susceptible preterm piglets. Virome transfer was equally effective as FFT in reducing the severity of NEC-like pathology. The bacterial compositional data corroborated clinical findings as virome transfer reduced the relative abundance of several NEC-associated pathogens e.g. Klebsiella pneumoniae and Clostridium perfringens . Virome transfer diversified gut viral communities with concomitant constraining effects on the bacterial composition. Unexpectedly, virome transfer, but not residual postbiotic fluid, led to earlier diarrhea. While diarrhea may be a minor concern in human infants, future work should identify ways of eliminating this side effect without losing treatment efficacy.

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Pediatric Fecal Microbiota Transplantation in Recurrent Clostridioides Difficile

Cited by 3 publications

References 57 publications

Fecal virome is sufficient to reduce necrotizing enterocolitis

Fecal virome is sufficient to reduce necrotizing enterocolitis

Precision medicine: Overview and challenges to clinical implementation

Fecal virus-like particles are sufficient to reduce necrotizing enterocolitis

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