Weight Loss

Jessica R. Allegretti, MD, MPH, on the Role of FMT in Weight Loss

The Centers for Disease Control and Prevention estimates that approximately 93.3 million US adults had obesity from 2015 to 2016.1 And according to the researchers of a pilot study, these people may have another option for weight loss treatment.2

The study, which was coauthored by Jessica R. Allegretti, MD, MPH, director of the Fecal Microbiota Transplant Program at Brigham and Women’s Hospital, investigated the impact that fecal microbiota transplant (FMT) from a lean donor has on a person with obesity who is metabolically normal. The results showed that it is safe for people with obesity to receive FMT from a person who is lean. In fact, such a transplant may lead to engraftment of donor-specific taxa.

Gastroenterology Consultant spoke with Dr Allegretti about the research and its implications for clinical practice.

Gastroenterology Consultant: In discovering that FMT from lean donors is safe, were there any surprises in your findings?

Jessica Allegretti: Unfortunately, it was ultimately a negative study for our primary outcome, which was a change in glucagon-like-peptide-1 (GLP-1). What I take away from it all is that perhaps GLP-1 was not the correct pathway on which to focus. We did ultimately assess many other variables, and we certainly learned quite a bit from the study. We noted significant changes in the bile acid profiles, so we are doing follow-up work on analyzing various metabolites. In turn, the obvious next steps would be analyzing the dosage—maybe the reason it was a negative trial was because we did not dose correctly. There are still many questions, but at least we come away with knowing that FMT was safe and well tolerated, and that we were able to achieve engraftment of that lean donor bacteria. Those are all very promising first steps, but a lot of work still needs to be done.

GASTRO CON: Do you have a timeline on when we can expect those next steps in research?

JA: That is the $1 million question—figuratively and legitimately, because it takes $1 million to fund the research. We are currently in the funding acquisition phase, but I do expect within the next year or so to at least be in the beginning steps. For some context, this placebo-controlled pilot trial took us about 4.5 years to do.

GASTRO CON: What are common questions you received from peers about your research?

JA: Many people have asked me why I picked the donor I chose, and I think it is a valid question. There are always questions surrounding the super-donor and what is the correct donor composition; we do not know the answer to that question. I suspect that the correct donor will be very different for every disease process, and what we have learned about inflammatory bowel disease, for instance, is very different than what is needed in obesity. We went into the study with the lean donor hypothesis. We wanted someone who is lean but also metabolically active, so the donor we chose actually ate, on average, significantly more calories than the standard female donor. Was that the correct hypothesis? I do not know, because we only had the 1 donor. Again, the next step will be answering 2 questions: What is the correct dose, and what is the ideal donor composition? We have to test a couple of hypotheses going forward to try to whittle down the correct answer.

GASTRO CON: What are the key takeaways from your study for practitioners?

JA: Two key takeaways are that FMT in metabolically uncompromised patients with obesity is safe and well tolerated, and a question on whether or not changes in GLP-1 and weight loss will occur among this patient population remains, because we did not see any. We were able to achieve engraftment, so hopefully with corrective or longer follow-up we will gain insight into these important clinical findings. 

GASTRO CON: How do you want your research to impact clinical practice going forward?

JA: We chose to do this study because we wanted to better understand this patient population. The big picture goal is to be able to have targeted, better therapy to help treat people with obesity, which is a huge health burden affecting many Americans. There are inadequate treatment options right now other than surgical options, which of course carry a risk of morbidity. We were hoping to start to unlock the understanding of pathology of this disease to ultimately be able to develop more advanced therapeutic options. There is still a long way to go, but we think this was an important first step.

References:

  1. Hales CM, Carroll MD, Fryar CD, Ogden CL. Prevalence of obesity among adults and youth: United States, 2015–2016. NCHS Data Brief. 2017;(288):1-8. https://www.cdc.gov/nchs/data/databriefs/db288.pdf. Accessed October 1, 2019. 
  2. Allegretti JR, Kassam Z, Mullish BH, et al. Effects of fecal microbiota transplantation with oral capsules in obese patients. Clin Gastroenterol Hepatol. 2019;pii:S1542-3565(19)30739-6. doi:10.1016/j.cgh.2019.07.006.