It’s simple: Eat less.
Sometimes combined with the directive move more, this mantra has a clear point. In case you can’t reduce weight, you might be either stupid or lazy—or, probably, both.
But if things were that simple, diets would work. Middle-aged people would not suddenly start increasing body weight despite eating and moving similarly every year. No one would need to endure the population of one friend with the “fast metabolism” who can eat anything he wants. And who, even though he knows you’re on any diet, says through his overstuffed mouth, “I couldn’t even add pounds in the event I tried.”
Instead, it is becoming clear that some people’s guts are simply more streamlined than others’ at extracting calories from food. When a couple eats the same 3,000-calorie pizza, for example, their bodies absorb different levels of energy. And those calorie-converting abilities can change over the person’s lifetime with age along with other variables.
The question is, why? And is it possible to make changes, in case a person needed to?
If so, the answer will involve the trillions of microbes in our intestines and how they operate in concert with another variable that’s just beginning to get attention. Your immunity determines stages of inflammation in the gut that are constantly shaping the way we digest food—how many calories get absorbed, and how many nutrients simply pass through.
The partnership between microbes and weight gain has long been overlooked in humans, but people have known about similar effects in animals for decades. After World War II, antibiotics became affordable and abundant for the first time. Farmers began giving the medication for their livestock—for example, as a treatment for a milk cow’s infected udder—and noticed that animals who got antibiotics grew larger and more quickly.
This led to a flood of patent applications for antibiotic-laden foods for every variety of livestock. In 1950, the medication company Merck filed a patent for “a method of accelerating the growth of animals” with “a novel growth-promoting factor” that has been, simply, penicillin. Eli Lilly patented three new antibiotics to mix directly into the feed of sheep, goats, and cattle because the microbe-killing agents “increased feed efficiency.” Within the ensuing decades, it became standard practice to give livestock copious doses of antibiotics to make them grow faster and larger, although no person knew why this happened, or what other effects the practice might have.
Researchers have only recently shown that these antibiotics kill off many of the microbes that occur normally in the gut and help livestock, and people, digest food. By breaking up nutrients and helping them flow through the walls of the bowel, these microbes function a sort of gatekeeper between what exactly is eaten as well as what makes it directly into the body.
Killing them is not without consequences. Similar to how antibiotics are associated with faster growth in cattle, a decrease in diversity in the human microbiome is associated with obesity. As the usage of animal antibiotics exploded in the twentieth, so too did usage in humans. Increase use of coincides having the obesity epidemic. This might be a spurious correlation, of course—lots of things have already been upon the rise since the ’50s. But dismissing it entirely would require ignoring a growing number of evidence that our metabolic health is inseparable beginning with the health in our gut microbes.
In 2006, Jeffrey Gordon, a biologist at Washington University in St. Louis, reported that the microbiomes of obese mice had something in accordance: In comparison to their lean counterparts, the heavier mice had fewer Bacteroides and more Firmicutes species within their guts. What’s more, biochemical analyses showed that this ratio made the microbes better at “energy harvest”—essentially, extracting calories from food and passing it into the human body. That is, even though mice ate precisely the same amount and kind of food, the bacterial populations meant that many developed metabolic problems, while some didn’t. Similar bacterial patterns have since been confirmed in obese humans.
What’s more, Gordon found, the microbiome associated with obesity is transferable. In 2013, his lab took gut bacteria from pairs of human twins in which only one twin was obese, then fed the samples to mice. The mice given bacteria beginning with the obese humans quickly gained weight. The others did not.
Intestinal microorganisms are likewise transferred between humans, using fecal transplants, as a possible experimental treatment for serious infections like Clostridium difficile. In one study, obese patients who received transplants from lean donors later had healthier responses to insulin.
Short of this kind of hard reset considering the microbiome, preliminary research has demonstrated that adding also a single bacterial species to the person’s gut can alter her metabolism. Within tests reported last month within the journal Nature Medicine, people who took a probiotic containing Akkermansia muciniphila—which is usually found in greater amounts in non-obese people—saw subtle metabolic improvements, including weight loss.
The research authors aren’t suggesting that anyone go out and obtain this bacterium. But is known as a “proof of concept” regarding the idea that it’s possible to change a person’s microbiome in ways which have metabolic benefits.
Because leanness and obesity seem to be transmissible throughout the microbiome, “metabolic disease turns out to be, in certain ways, like an infectious disease,” says Lora Hooper, the chair considering the immunology department at the University of Texas Southwestern Hospital. Hooper did her postdoctoral research in Gordon’s lab in St. Louis. While other researchers focused on the gut microbiome itself, she took an interest within the immunity. Specifically, she wanted to know how an inflammatory response could influence these microscopic populations, and thus be related to gaining weight.
During the last decade or so, multiple studies have proven that obese adults mount less effective immune responses to vaccinations, and also that both overweight and underweight people have elevated rates of infection. But these were long assumed to become effects of obesity, not causes.
“When I started my lab there wasn’t much found how immunity perceives the gut microbes,” Hooper says. “Many people thought the gut immunity might be the type of blind to them.” To her, it was obvious that this couldn’t be the case. A person’s gut is host to be about 100 trillion bacteria. They serve vital metabolic functions, but can quickly kill someone if they get into the bloodstream. “So clearly the immune system has got to become involved in maintaining them,” she says. It made sense to her that even subtle changes within the functioning of the immunity could influence microbial populations—and, hence, gaining weight and metabolism.
This theory was confirmed late last month in a paper in Science. Zac Stephens, a microbial ecologist with the University of Utah, and his colleagues had been collaborating with mice with altered immune T cells. They noticed that over time, these mice “ballooned,” as Stephens puts it. One of his colleagues started summoning them “pancakes.”
To determine how such an immune change may cause obesity, they tested the biomes considering the mice with and without having the immune alteration. They found that healthy mice have lots of bacteria coming from a genus called Clostridia, but few from Desulfovibrio, and also that their guts let most fat pass throughout. People who have a restructured immune system had fewer Clostridia and more Desulfovibrio, and this microbial balance helped the gut absorb more fats from food. These mice gained more weight and exhibited indications of diabetes type 2.
“Whether this applies in humans, we don’t know,” Hooper says, “but this can be a tantalizing clue.”
Mice aren’t humans, but their microbiomes are about as complex as our own. Reduced Clostridia and increased Desulfovibrio are seen in people with obesity and kind 2 diabetes. Bacteria can reasonably be expected to operate similarly within the guts of different species. But even if they can don’t, this experiment is a demonstration of principle: The immune system helps control the composition of the gut microbiome.
It does so by regularly mounting low-level immune responses to maintain populations of bacteria in order. “The gut is under a continuing state of inflammation, so to speak—constant immune stimulation from all the microbes,” says Stephens, pushing back upon the common misconception that inflammation is always bad. The role of considering the immune system within the gut would be to maintain balance. Changes to the body’s defenses, which could happen due to age or illness, can cause certain species to flourish in exchange for others.
This is the interesting part to Steven Lindemann, a researcher at Purdue University who was not involved in the Utah study. He studies the effects of foods upon the gut microbiome. “Although we all know that, on the balance, diet is the strongest contributor to gut microbiome composition,” he explained, this study means that when immune control over the colon stops working, growth could become unchecked and lead to further problems with metabolic regulation.
Lindemann says the fact that your immunity regulates the inhabitants of the small intestine is well established. He compares the bowel wall to the customs checkpoint: The goal is to weed out bad actors and illegal cargo, but allow legitimate trade to progress as regularly as possible. In the case of the immune-altered mice, he states, “we have a colonic border patrol that’s seemingly purpose is to lunch, allowing bad actor Desulfovibrio to bloom.”
If similar microbial changes have comparable effects in humans, it very well could have far-reaching implications for our particular diets. The very ideas of “nutritional value” and “calorie content” of food seem to vary based on the microbial population of the individual eating it and, potentially, her immune status. A person’s microbes—and those contained in any given food—would need to be regarded as another component considering the already flimsy calories-in, calories-out equation. This would also compound the difficulties already facing nutrition labels.
People trying to control their weight might conclude that tinkering with their microbiomes is the solution. This stands to support the already dubious and barely regulated industry of “probiotic” supplements, that have been projected to progress to $7 billion by 2025. But the answer probably won’t be so simple.
“A lot of the most recent research on probiotics suggests it’s really hard to keep and sustain new communities,” Stephens says. The immune system could explain that. “It might be that your immune response gets ‘stuck’ from a young age based upon what you’ve exposed it into. Probiotics might not be enough to change a person’s microbiome, because your immune system determined ahead of time that certain microbes are either appropriate or inappropriate in your gut.”
Stephens says the relationship between weight and the immune system will probably have got a lot more complicated before it gets simpler. Which makes it hard to give concrete advice. “Keeping diverse gut microbes with diverse dietary sources is perhaps the safest advice for now,” he states. “That will stimulate the ideal, strong immunity that can learn and regulate and do all the things it does, in ways we’re just beginning to comprehend.”
If all this uncertainty makes nutrition guidelines and nutrition even more inscrutable, additionally it stands to carry out some great by undermining the moralizing and simplistic character judgments often associated with body mass. Seeing obesity being a manifestation of the interplay between many systems—genetic, microbial, environmental—invites the realization that human physiology has changed along with our relationship to the species in and around us. As these new scientific models unfold, they impugn the thought of weight as a possible individual character flaw, revealing it regarding the self-destructive myth it has always been.
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