Two experts debated the role of the microbiome in human obesity, with potential therapeutic implications. The notion that the microbiome plays a role in obesity is all hype, asserted Max Nieuwdorp, MD, PhD, while Rob Knight, PhD, supported the argument that the microbiome is key in obesity.
Hope or Hype—Role of Microbiome in Obesity can be viewed on-demand by registered meeting participants at ADA2023.org. If you haven’t registered for the 83rd Scientific Sessions, register today to access the valuable meeting content through August 28.
Research into microbiomics in this field kicked off with a seminal paper in 2004 that found that gut microbiota regulate fat storage, noted Dr. Nieuwdorp, Full Professor of Internal Medicine at Amsterdam UMC Diabetes Center in The Netherlands. There were also several relatively large trials 10 years ago that studied hundreds of patients.
“Most of what my opponent shows you are association studies. But when you start doing the intervention with bacterial strains or fecal matter transplant, there’s no effect on obesity, weight or BMI (body mass index), although it does do something on insulin resistance,” Dr. Nieuwdorp said.
Part of the problem is that scientists have no reference values, and that much of the research, which is done by means of observational studies, suffers from bias, he said. Another difficulty is that half of the studies are done in murine models, and while diet is responsible for half of the changes in the gut microbiota of mice, diet only accounts for 5%-10% of that change in humans. Additionally, when participants are asked to complete questionnaires that describe what they’re eating, humans often lie.
“However, in the insulin resistance part, there might be some hope on the horizon, because it can produce an effect, at least temporarily, in the preclinical phase of metabolic syndrome and diabetes,” Dr. Nieuwdorp said.
The microbiome accounts for 99% of the genes in a human, and personalized therapies for obesity, such as fecal matter transplant, hold potential for addressing the epidemic in the U.S., according to Dr. Knight, Wolfe Family Endowed Chair of Microbiome Research at Rady Children’s Hospital of San Diego and Professor of Pediatrics, Computer Science, and Engineering at the University of California, San Diego.
Dr. Knight and his colleagues performed a study a decade ago in germ-free mice raised in a bubble and found that if they were given microbes from a fat mouse, but not a lean mouse, the mice became obese. The same thing happened if the mouse was given genes from an obese or a lean human.
“You heard some complaints about causality. This does demonstrate causality from the microbiome in a mammalian model,” Dr. Knight said.
Dr. Knight also cited data from a study of 800 people that found that gut microbes were primarily what determined whether it was healthier for an individual to eat ice cream or rice. Dr. Knight is on the scientific advisory board of a company that commercialized a test to determine which category an individual falls in based on their gut microbiota.
Another study of four patients with Clostridioides difficile, or C. diff, found that a fecal transplant of a few grams of stool from a healthy donor resets their microbiome to a healthy state completely within two to three days.
“That’s what it does in 90%-95% of C. diff cases,” said Dr. Knight.
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