Opinion: Splashing cold water on poo transplants for weight loss | Abstract TS

Oyour guts teem with life. Billions of bacteria, viruses and fungi call our gastrointestinal metropolises home. Single-celled microorganisms help break down complex carbohydrates and build vitamins. They patrol dark alleys to ward off pesky pathogens. They send signals through our intestinal tract and beyond. Scientists have spent decades studying these microbial citizens because unlocking their secrets could help understand, prevent and treat diseases ranging from heart disease to Alzheimer’s disease.

With half of all americans To have clinical obesity by 2030, weight loss applications may be the most promising front in gut microbiome research. In 2013, Lee Kaplan and Jeffrey Gordon, gastroenterologists at Massachusetts General Hospital (my home institution) and Washington University School of Medicine in St. Louis, respectively, conducted separate studies demonstrating this potential. In Kaplan’s study, published in Science Translational Medicine, mice that underwent weight loss surgery saw a remarkable change in their gut microbiome. And when these microbes were transplanted into the intestines of other mice, the recipients also experienced rapid weight loss. With fecal microbiota transplantation (FMT), Kaplan could achieve 20% of the benefits of bariatric surgery, without the surgery (5:178ra41).

Without a more targeted strategy, obesity may decrease. We need a scalpel, not a hammer.

In Gordon’s study, published in Science, mice received feces from human twins, one suffering from obesity and the other not. Mice that received the feces from the lean twin remained lean while those that received the feces from the obese twin gained weight. Additionally, housing the two recipient mice together so they could eat each other’s feces – which the mice actually do – allowed the heaviest mouse to lose weight, provided they were all fed a low-fat diet (341:1241214). The next step, said Gordon The New York Timeswas to determine which gut bacterial species induce thinness to give patients these specific microbes as a treatment for obesity.

Fast forward a decade, and we’ve moved on to human-to-human FMT experiences. Elaine Yu, a mass general endocrinologist, and Jessica Allegretti, a gastroenterologist at Brigham and Women’s Hospital, are conducting separate clinical trials with so-called “blind” FMT. In other words, they’re trying to examine whether oral capsules containing skinny donor feces — crapsules, if you will — can help obese patients lose weight. Despite the initial enthusiasm, the preliminary results published a few years ago by the two Yu’s trial and Allegretti’s trial showed no significant change in body weight. Without a more targeted strategy, hope for a microbial-based treatment for obesity may be dwindling. We need a scalpel, not a hammer.

Nonetheless, these sobering results have done little to stem the hype surrounding FMT and microbial therapies more broadly. Boston-based startup Finch Therapeutics, a partner in Allegretti’s trial, raised approximately $130 million the first day it went public in March 2021 on the promise of its freeze-dried poo pills treating everything from Crohn’s disease to obesity. However, the company does not yet have any products on the market. Similarly, microbiome researcher Jeff Leach got national media coverage for using a turkey baster to seed his intestines with the feces of a Tanzanian Hadza tribesman – a do-it-yourself FMT. (He earned the nickname “Doctor Shit” in Swahili.) Leach was trying to “regenerate” his gut microbiome from its supposedly unhealthy, industrialized state – a state that research has shown is associated with obesity, diabetes and other chronic diseases – to a purportedly more healthy and ancestral state. Many companies in the weight loss supplement industry, estimated to $94.5 billion in 2022, have also jumped on this bandwagon, peddling questionable weight loss claims about their prebiotics and probiotics.

Perhaps it’s the supposed ease of the solution that explains the unbridled excitement around a microbial treatment for obesity. The root causes of obesity are often mistakenly boiled down to failures in diet or exercise; the condition is commonly conceptualized as a lifestyle disease caused by bad behavior. So rather than resorting to the seeming extremes of drug therapy or bariatric surgery, a more “natural” option, like taking poop pills, has some appeal. But this approach may risk having potential off-target effects by altering the gut microbiome. For example, in at least one case, someone developed recurrent obesity after getting an FMT to treat Clostridium difficile infection, for which FMT is the standard of care. Thus, transforming the gut microbiome solely in the name of weight loss might not be safe or feasible. What new problems might we create with this myopic focus?

Maybe we’ll eventually figure out how to shape our gut microbiome to target obesity. Maybe not. There are obviously reasons to be optimistic, but not yet enough evidence to justify all the hype, especially because this nascent science is often distorted in the name of profit. Obesity is a complex chronic disease that is influenced by the gut microbiota but not necessarily a disease of the gut microbiota. The treatment of obesity therefore requires multimodal solutions. Despite centuries of trying to pinpoint the problem to a single culprit and identify an easy fix, there is no silver bullet.

Simar Bajaj is a researcher at Massachusetts General Hospital and Stanford University School of Medicine, where he studies obesity and cardiothoracic surgery.

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