Meeting News

FMT safe in patients with obesity, more research needed

Jessica Allegretti

Researchers successfully engrafted microbiota to patients with obesity using stool from lean donors, giving them optimism about the future of fecal microbiota transplantation as a treatment for obesity.

Jessica R. Allegretti, MD, director of the FMT program at Brigham and Women’s Hospital, will present data from the study later this month at Digestive Disease Week in San Diego. On a conference call, she said researchers specifically wanted to look at patients with obesity who were still otherwise healthy.

“In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but they still have difficultly losing weight,” she said. “During our research, we wanted to focus on and understand that this is a very important population, which we call ‘metabolically uncompromised obese,’ and understand if FMT might be a viable treatment option for them.”

Researchers performed a parallel study of patients with obesity (BMI 35 kg/m²) who were metabolically healthy, defined as no type 2 diabetes, nonalcoholic steatohepatitis or metabolic syndrome (n = 22). They randomly assigned patients to 30 FMT capsules followed by two doses of 12 capsules for 12 weeks or identical placebo capsules.

Investigators collected stool samples at baseline and weeks 1, 4, 6, 8 and 12 after FMT and measured glucagon-like peptide-1 (GLP-1) and leptin. Change in the area under the curve for GLP-1, along with safety, was the primary outcome of the study. Researchers also explored gut microbiota profiles and diversity, as well as bile acid at 12 weeks after FMT as secondary endpoints.

Allegretti said there was no increase in the AUC of GLP-1 or early changes in BMI noted in either group at week 12. Therefore, the study failed to meet its primary endpoint.

However, there were no serious adverse events, and investigators observed global signals of donor community engraftment after FMT. This included increases in alpha diversity and similarity to stool samples from the donor that were not observed in the placebo arm of the study.

Additionally, researchers observed a decrease in bile acids among FMT recipients, which could ultimately benefit weight loss.

Allegretti said they will do further research to determine if GLP-1 is the right target, if they need a more sensitive assay for GLP-1 or if they need to change the FMT dosing in the study.

“We believe obesity is a very complex disorder that is developed with a multifactorial process,” Allegretti concluded. “We certainly hope our research will lend itself to understanding this a bit better and, hopefully, more targeted therapies in the future.” – by Alex Young

Reference:

Allegretti JR, et al. Abstract 621. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Allegretti reports she has financial ties to Finch Therapeutics, Janssen and Merck. Please see the DDW disclosure index for all other authors’ relevant financial disclosures.

 

Jessica Allegretti

Researchers successfully engrafted microbiota to patients with obesity using stool from lean donors, giving them optimism about the future of fecal microbiota transplantation as a treatment for obesity.

Jessica R. Allegretti, MD, director of the FMT program at Brigham and Women’s Hospital, will present data from the study later this month at Digestive Disease Week in San Diego. On a conference call, she said researchers specifically wanted to look at patients with obesity who were still otherwise healthy.

“In my clinical practice, we regularly see patients who have not yet developed some of these other conditions related to obesity, but they still have difficultly losing weight,” she said. “During our research, we wanted to focus on and understand that this is a very important population, which we call ‘metabolically uncompromised obese,’ and understand if FMT might be a viable treatment option for them.”

Researchers performed a parallel study of patients with obesity (BMI 35 kg/m²) who were metabolically healthy, defined as no type 2 diabetes, nonalcoholic steatohepatitis or metabolic syndrome (n = 22). They randomly assigned patients to 30 FMT capsules followed by two doses of 12 capsules for 12 weeks or identical placebo capsules.

Investigators collected stool samples at baseline and weeks 1, 4, 6, 8 and 12 after FMT and measured glucagon-like peptide-1 (GLP-1) and leptin. Change in the area under the curve for GLP-1, along with safety, was the primary outcome of the study. Researchers also explored gut microbiota profiles and diversity, as well as bile acid at 12 weeks after FMT as secondary endpoints.

Allegretti said there was no increase in the AUC of GLP-1 or early changes in BMI noted in either group at week 12. Therefore, the study failed to meet its primary endpoint.

However, there were no serious adverse events, and investigators observed global signals of donor community engraftment after FMT. This included increases in alpha diversity and similarity to stool samples from the donor that were not observed in the placebo arm of the study.

Additionally, researchers observed a decrease in bile acids among FMT recipients, which could ultimately benefit weight loss.

Allegretti said they will do further research to determine if GLP-1 is the right target, if they need a more sensitive assay for GLP-1 or if they need to change the FMT dosing in the study.

“We believe obesity is a very complex disorder that is developed with a multifactorial process,” Allegretti concluded. “We certainly hope our research will lend itself to understanding this a bit better and, hopefully, more targeted therapies in the future.” – by Alex Young

Reference:

Allegretti JR, et al. Abstract 621. Presented at: Digestive Disease Week; May 18-21, 2019; San Diego.

Disclosures: Allegretti reports she has financial ties to Finch Therapeutics, Janssen and Merck. Please see the DDW disclosure index for all other authors’ relevant financial disclosures.

 

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