In the Journals

Fecal microbiota transplant reduces prevalence of AMR genes in children

Photo of Suchitra Hourigan
Suchitra K. Hourigan

Children who underwent fecal microbiota transplant, or FMT, experienced a significant reduction in recurrent Clostridioides difficile infection, or CDI, and a decrease in the prevalence of antimicrobial resistance genes in their gut microbiota, according to findings published in Open Forum Infectious Diseases.

C. difficile infection causes significant morbidity and is increasing in prevalence in children,” Suchitra K. Hourigan, MD, a board-certified pediatric gastroenterologist at Pediatric Specialists of Virginia, told Infectious Diseases in Children. “FMT has been shown to be an effective treatment for recurrent C. difficile and has now been included in recent practice guidelines for treatment of recurrent C. difficile for both adults and children, although only certain pediatric centers currently offer this as an option.”

Hourigan said the mechanisms that make FMT work have not been fully explained, but it has been suggested that FMT restores the intestinal microbiome. A recent FDA warning on the transfer of multidrug-resistant organisms to an FMT recipient spurred the study, she said.

According to Hourigan and colleagues, most children receiving FMT have adult donors, and the differences between the adult and developing child’s gut microbiome could be concerning.

For the study, nine children without underlying inflammatory bowel disease and with recurrent CDI underwent FMT. The researchers collected stool samples from both the children and their donors before FMT and after FMT for up to 24 weeks.

Hourigan and colleagues noted that all recurrent CDI among children in the study resolved after FMT, and that antimicrobial resistance genes also decreased after transplantation (P < .001). However, the researchers identified an increase in genes related to tetracycline resistance following FMT (P < .001).

Both donors and children had very low levels of potential pathogens, but the overall level among children undergoing FMT decreased after transplant (P < .001). After undergoing FMT, all children had an expansion of Prevotella species 109 — a strain of a gram-negative bacteria — but no clinical infections occurred.

Before transplant, children had significantly lower alpha-diversity compared with donors. Alpha-diversity increased after FMT (P .002) and was sustained at follow-up.

According to the researchers, beta-diversity differed significantly between children before and after FMT. Donors were more likely to have Faecalibacterium prausnitzii and Bacteroides ovatus (P = .008) compared with recipients (P = .04). However, expansion increased after FMT for children. Furthermore, the researchers said biosynthetic pathways were most common among donors and increased among children following transplant.

Photo of Keith Crandall
Keith A. Crandall

Study author Maria M. Oliva-Hemker, MD, director of the division of pediatric gastroenterology, hepatology and nutrition and professor of pediatrics at Johns Hopkins Medicine, told Infectious Diseases in Children that data suggest that FMT is safe for children receiving the procedure for the treatment of recurrent or refractory CDI. However, she said little is known about the long-term effects.

“Many parents view FMT as safe because they believe it is ‘natural,’” she said. “There are parents who wish to have their children undergo this for management of chronic gastrointestinal symptoms or other conditions such as autism. It needs to be kept in mind that other than for the treatment or recurrent or refractory C. difficile, FMT is considered an experimental procedure and should only be done in children under research protocols approved by institutional review boards.”

Keith A. Crandall, PhD, study author and professor of biostatistics and bioinformatics at George Washington University, said the study’s small sample size and two different types of donor material means researchers cannot draw any conclusions about the safety of donor material or the efficacy of “related” donor material compared with “commercial” donor material.

“Our study clearly has some very interesting and exciting insights to justify the efficacy of FMT in children,” he told Infectious Diseases in Children. “However, there is much work yet to do, and we envision continuing our research with larger sample sizes and a greater diversity of patients.” – by Katherine Bortz

Disclosures: Crandall reports relevant financial activities outside of the submitted work. Hourigan and Oliva-Hemker report no relevant financial disclosures.

Photo of Suchitra Hourigan
Suchitra K. Hourigan

Children who underwent fecal microbiota transplant, or FMT, experienced a significant reduction in recurrent Clostridioides difficile infection, or CDI, and a decrease in the prevalence of antimicrobial resistance genes in their gut microbiota, according to findings published in Open Forum Infectious Diseases.

C. difficile infection causes significant morbidity and is increasing in prevalence in children,” Suchitra K. Hourigan, MD, a board-certified pediatric gastroenterologist at Pediatric Specialists of Virginia, told Infectious Diseases in Children. “FMT has been shown to be an effective treatment for recurrent C. difficile and has now been included in recent practice guidelines for treatment of recurrent C. difficile for both adults and children, although only certain pediatric centers currently offer this as an option.”

Hourigan said the mechanisms that make FMT work have not been fully explained, but it has been suggested that FMT restores the intestinal microbiome. A recent FDA warning on the transfer of multidrug-resistant organisms to an FMT recipient spurred the study, she said.

According to Hourigan and colleagues, most children receiving FMT have adult donors, and the differences between the adult and developing child’s gut microbiome could be concerning.

For the study, nine children without underlying inflammatory bowel disease and with recurrent CDI underwent FMT. The researchers collected stool samples from both the children and their donors before FMT and after FMT for up to 24 weeks.

Hourigan and colleagues noted that all recurrent CDI among children in the study resolved after FMT, and that antimicrobial resistance genes also decreased after transplantation (P < .001). However, the researchers identified an increase in genes related to tetracycline resistance following FMT (P < .001).

Both donors and children had very low levels of potential pathogens, but the overall level among children undergoing FMT decreased after transplant (P < .001). After undergoing FMT, all children had an expansion of Prevotella species 109 — a strain of a gram-negative bacteria — but no clinical infections occurred.

Before transplant, children had significantly lower alpha-diversity compared with donors. Alpha-diversity increased after FMT (P .002) and was sustained at follow-up.

According to the researchers, beta-diversity differed significantly between children before and after FMT. Donors were more likely to have Faecalibacterium prausnitzii and Bacteroides ovatus (P = .008) compared with recipients (P = .04). However, expansion increased after FMT for children. Furthermore, the researchers said biosynthetic pathways were most common among donors and increased among children following transplant.

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Photo of Keith Crandall
Keith A. Crandall

Study author Maria M. Oliva-Hemker, MD, director of the division of pediatric gastroenterology, hepatology and nutrition and professor of pediatrics at Johns Hopkins Medicine, told Infectious Diseases in Children that data suggest that FMT is safe for children receiving the procedure for the treatment of recurrent or refractory CDI. However, she said little is known about the long-term effects.

“Many parents view FMT as safe because they believe it is ‘natural,’” she said. “There are parents who wish to have their children undergo this for management of chronic gastrointestinal symptoms or other conditions such as autism. It needs to be kept in mind that other than for the treatment or recurrent or refractory C. difficile, FMT is considered an experimental procedure and should only be done in children under research protocols approved by institutional review boards.”

Keith A. Crandall, PhD, study author and professor of biostatistics and bioinformatics at George Washington University, said the study’s small sample size and two different types of donor material means researchers cannot draw any conclusions about the safety of donor material or the efficacy of “related” donor material compared with “commercial” donor material.

“Our study clearly has some very interesting and exciting insights to justify the efficacy of FMT in children,” he told Infectious Diseases in Children. “However, there is much work yet to do, and we envision continuing our research with larger sample sizes and a greater diversity of patients.” – by Katherine Bortz

Disclosures: Crandall reports relevant financial activities outside of the submitted work. Hourigan and Oliva-Hemker report no relevant financial disclosures.

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