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.

Figure 1: Comparison of complex and restrictive diets. A complex diet, one that contains all macronutrients, feeds colon microbes, which in turn release necessary molecules from the large intestine (left). Decreased variety in diet shifts uptake to the small intestine and leads to an imbalance in the microbiome (right).

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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14 thoughts on “Eating for a Trillion: Can your microbiome be the key to long-lasting weight loss?

  1. Hi, thank you so much for this insightful post. I do also have a suggestion for people who want to lose weight, you can try this weight loss product. It really helped me to get a fit body.

  2. “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.”

    What is up with this either ignorant or deceitful anti-paleo propaganda? You know that is a misleading presentation of the info. This is the same Harvard that earlier last century took money from sugar lobbyists to defend sugar and falsely put the blame on fat. Do you know no shame?

    A paleo diet may or may not be a low carb diet. It’s simply based on what we know about hunter-gatherers eat and what hominids have eaten for millions of years. As for hunter-gatherers, it’s true that most eat far less carbs than do those on the modern Western diet, although some eat a higher carb diet.

    The difference is what kind of carbs, more often tubers and rarely grains or legumes. Also, they eat a lot of fiber, which is why most advocates of the paleo diet follow a high-fiber diet, more fiber probably than consumed than by the average vegetarian and vegan.

    The paleo diet has been linked to no diseases. And neither has the ketogenic diet. Quite the opposite. To state otherwise is a baldfaced lie. It is also a lie to imply that a ketogenic diet is a “high fat diet increased obesity and fat storage,” since for most people fat is only fattening when combined with carbs, something we know from diverse scientific research and anthropological literature.

    If you knew the slightest thing about a ketogenic diet, you’d know that scientifically-speaking it doesn’t equate to a high-fat diet. All that is required to be in ketosis is for there to be restricted carbs, but this can be achieved with low-to-moderate fat intake. Monks regularly combine a plant-based diet (often vegan or vegetarian) with calorie restriction and fasting, which is another form of ketogenic diet.

    What is you point in bringing up the fact that, “saturated fats leads to microbial imbalance”? Many paleo advocates have more intelligent commentary about saturated fat than found in this article. Even for paleo dieters who follow a high-fat diet, most try to maintain the traditional balance with omega-3s that has been standard for most of human existence. The average American, including the average vegetarian, gets a greater imbalance of saturated fats (the latter from dairy).

    Yes, some of the limits of research mean “scientists don’t really know yet what this diet could do.” Yet it doesn’t stop you from making ignorant speculations and unfounded assertions. Who is paying you enough that you are willing to public dishonor and delegitimize yourself?

    1. Benjamin —

      An actual ketogenic diet is designed to have no carbs, not a lot of protein, and 85-90% fat. It was then “recreated” to incorporate more protein due to muscle loss and lack of building muscle. But it did not incorporate the carbohydrates, less than 5%. Just an FYI. This information in the article is accurate if you research it properly..

      1. Sorry Virginia,

        The statement that Paleo is a low carb diet could not be more ignorant or inaccurate.

        1. Paleo has been marketed by the most influential Paleo promoters as a low carb diet. Paleo is not just a low carb diet but lowering carbs is a big basis of the Paleo diet. You are disingenuous to argue differently.

      2. If you researched it properly, you’d know that almost ALL of the research suggests closer to a 70:25:5 split of fat:protein:carbs. While the numbers fluctuate depending on the research and who you ask, I have NEVER in my years of studying the topic seen a fat percentage higher than 80% — so to even imply 95% is ludicrous.

        Additionally, almost nobody recommends eating 0g daily carbs — I’ve seen numbers between 20g and 100g, but never 0g.

        Furthermore… nevermind. This isn’t even worth debating with you.

    2. Thanks Benjamin.

      As I was reading this, I knew I was going to have to respond.

      Can you imagine the damage the author has done to those just beginning their own journey in learning about their own health? Shameful.

  3. The truth is that the Paleo Diet will never be considered a fad because it’s just simply the way that humans evolved to eat over approximately 2 million years. And eating in a similar fashion to our ancestors has been proven time and time again to offer amazing health benefits, including prevention of most diseases of civilization such as cancer, heart disease, Alzheimer’s, and other chronic conditions that are mostly caused by poor diet and lifestyle. One of the biggest misunderstandings about the Paleo Diet is that it’s a meat-eating diet or a super low-carb diet.

      1. Other than infectious diseases, hunter-gatherers have an average lifespan equivalent to modern societies. And many of the infectious diseases were introduced by outsiders. Even malaria is thought to have originated among farming communities. In any case, the only factors shortening their lives are non-dietary. This kind of data is common knowledge at this point.

    1. That’s not true. You are believing what a few people are saying based on their preconceived ideas and interpretation of limited data and knowledge. Watch a Ted talk about there being no such thing as the paleo diet. I can’t remember the exact title but if you search paleo diet and Ted talk on YouTube you’ll find it. It’s presented by a lady who is a scientist like an anthropologist and or archeologist. She shows how in reality, people groups in different parts of the world have been eating very different diets based on their micro climate for all of history and they find evidence of grain and legume and tuber eating from very early.

  4. Overall, it looks like a balance of bacteria in the gut is the key to balance in fat storage and energy use. As well, overall health is largely affected by bacteria activity that keys hormones in our bodies, signaling energy storage and use- as well as basic neurological daily functions. Apparently, gut bacteria communicates through the pheromones that are produced by each group of bacteria type, and that communication might be balanced and controllable by introducing “false Flags” ( specific pheromones) that “trick” certain bacteria to increase or decrease activity. However, with SO MANY different bacteria in our bodies, the permutations of interactions must be a probability problem that can only be modeled properly by the time tested evolution of these basic interactions. Currently, processed foods, specific diets, lack of daily exercise, water starvation, all tax the ability of our evolved bacteriological systems to stay in balance. Just being sure that there is enough “selection” of available bacteria present in our bodies , I think, is a good idea. Let evolution sort out the balances, and simply keep up the basics of exercise, water, balance of diet, and–(I Think) probiotics to assure a good selection of bacteria . That is what I am doing. I hear Ray Kurtzweil takes a hundred pills a day? Yet, he also has a clone in the closet for good measure, in case of miss-calculation. Unaffordable for me.

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