by Jemila C Kester, PhD

figures by Rebecca Clements

In the Seinfeld episode “The Stranded,” Jerry is choosing between two cold medicines. “This is quick-acting, but this is long-lasting,” he notes. “When do I need to feel good, now or later?” We often face a similar dilemma when choosing a particular diet as weight-loss “medicine.” With a third of American adults overweight , there’s a veritable buffet of options. But which diets are best?

Fad diets —weight-loss diets promising quick results based on scant scientific evidence—are the quick-acting pill. While fad diets can lead to quick weight loss in some dieters , most regain the weight within the first year .

In a recent study , researchers found a direct connection between gut bacteria and dieting efficacy. Along with many other studies , their data suggest the long-lasting pill might be found by feeding your gut microbiome —the trillions of microorganisms living in your intestines and their respective genes.

Failure Now: The role of the microbiome in losing weight

Have you ever started a diet with a friend, and while they are dropping pounds left and right, you struggle to nudge the scale at all? How is that possible, when you are both eating similarly? Depending on your microbiome, you might not be taking up and using equal energy from the same food. We are taught that what we eat gets broken down and absorbed in our intestines and either burned for energy or stored as fat. Except there’s more to it than that.

Food is mechanically and chemically broken down in the stomach. Next, it travels to the small intestine where enzymes break down the food even more into parts small enough to be absorbed into the body’s circulation and used for fuel.

The nuance arises from what happens to the food we can’t process. As humans, we don’t make the enzymes required to break down 45-65% of what our species has historically eaten , namely indigestible carbohydrates, or fiber. This indigestible portion of what we eat travels to our large intestine (also called the colon), where the resident microbes break it down for us, releasing molecules we are able to absorb and use.

Even when you and your friend eat the same amount, you might take up and use different amounts of calories from the same food, partly due to differences between your gut microbiomes . Variation between gut microbiomes is extremely high. While humans are 99% genetically identical, their microbiomes are only 50% the same , on average. These differences lead to differences in function. In short, intake doesn’t always mean uptake. In fact, microbiomes isolated from obese individuals have been shown to harvest more energy from the same amount of food . Therefore, changing what you eat may not reduce your caloric uptake linearly, depending on your personal microbiome.

Failure Later: The role of the microbiome in keeping weight off

What most fad diets have in common, beyond calorie restriction, is reduced variety. Many popular diets call for the reduction in—or even exclusion of—a macronutrient: carbohydrates, proteins or fats, primarily. While cutting out a macronutrient can lead to fast weight loss in up to 15% of dieters , it fails to maintain weight loss, with 95-99% regaining the weight with a year . This is partially because eliminating entire pieces of our diet is not sustainable mentally, and can even lead to stress, anxiety, and other mental health issues . New research suggests it’s also partly because of your microbiome and how a macronutrient-restrictive diet can affect it.

Complex carbohydrates are needed to maintain microbial richness in the gut, a hallmark of a functioning system. Low carb diets, like the Paleo diet, have been linked to less total bacteria and fewer of the bacteria found in the guts of healthy people. This microbial imbalance—termed dysbiosis—has been linked to many diseases , from autoimmunity, to metabolic and GI-tract disorders, to anxiety and depression.

Low fiber diets, specifically, are particularly deleterious. Diets high in simple carbs but low in fiber cause sugar and fat to be absorbed too early by the small intestine and go straight to the bloodstream. In addition to weight gain and increased fat storage from elevated blood sugar levels, these diets rob the large intestine dwellers of their meal, a likely cause of the dysbiosis seen with this diet (Figure 1). Conversely, diets high in fiber shift nutrient uptake to the colon, which can drive lower fat in the body and boost your ‘metabolism’ .

Protein is another macronutrient often on the chopping block with fad diets. There are conflicting results from studies looking at low protein diets, but most experts agree that plant-derived proteins have a better effect than animal-derived ones on gut health. This could be due to the higher fat content in animal-derived proteins.

Popular right now, the ketogenic diet is a low carb, high fat diet. In addition to the deleterious effects of reduced diversity and low fiber diets discussed above, new research on the ketogenic diet shows that it alters the gut microbiomes of mice by increasing the mucus-degrading bacterium Akkermansia muciniphila—a bug linked to both health and disease , meaning scientists don’t really know yet what this diet could do. Additionally, a recent study comparing several fad diets found that a high fat diet increased obesity and fat storage, and other work showed eating saturated fats leads to microbial imbalance. Together, these data suggest a high fat diet is suboptimal for lasting weight loss.

What is the long-lasting pill?

Altering your diet drastically might have lasting effects—and not the ones you’re aiming for. Fad diets call for less dietary diversity and therefore likely lead to reduced quantity and quality of your microbiome, which is associated with many health issues, including metabolic disorders and obesity .

Microbiome composition can affect weight loss , suggesting that eating for the trillions of microbes in our guts might be the key to achieving and maintaining a healthy weight . Still, more research is needed. To date, scientists have been unable to define a healthy microbiome by its constituents alone. This is likely because of the incredibly high variation of gut microbiota between individuals. In addition, “healthy” study participants are frequently on a Western diet (typically high in saturated fats and animal-derived proteins, low in fiber, and associated with weight gain ), which could confound results .

Future research will continue to expand our understanding of the microbiome and suggest ways to manipulate it to achieve our weight-loss goals. For now, this much is clear: eating a complex diet including all macronutrients seems to be the long-lasting weight-loss pill—for now and for later.

Jemila Kester earned her PhD in microbiology from the Harvard University in 2017. She is currently a postdoctoral associate at MIT. She lives in Cambridge, MA with her husband, their two daughters, and Steve the Dog.

Rebecca Clements is a third-year Ph.D. candidate in the Biological and Biomedical Sciences program at Harvard.

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