Fast food, gut microbes, sweet drinks, desk jobs: over the years, obesity has been blamed on many things. A Time-Life book on food and nutrition from 1967 implicated—among other things—cars. “The automobile has almost eliminated walking,” write the authors. “This decrease in exercise, which reduces the requirement for calories, has not always been accompanied by a corresponding decrease in appetite.”
Cars clearly don’t account for the doubling of obesity worldwide since 1980. The truth is, there’s much we still don’t know about why people put on weight. Obesity is a complex disorder, and by now it’s clear that the simple explanation of “too many calories” doesn’t tell the whole story. Plenty of doctors will tell you they know people who eat well and exercise without being able to keep the weight off.
Scientific evidence is beginning to accumulate suggesting that obesity is, in part, a disease of inflammation—that is, of immune system activity gone awry. Obese individuals show immune abnormalities, with different macrophages (specialized immune system cells that engulf and destroy other cells) dominating in the body’s fat tissue than in lean individuals. And part of the close link between the immune and metabolic systems could involve the gut microbiota.
Increasing scientific evidence suggests that obesity is, in part, a disease related to inflammation
One of the leading theories on the mechanisms leading to obesity, with evidence from both mouse models and humans, incorporates both the gut microbiota and inflammatory processes. According to this theory, a key feature for initiating obesity is permeability of the gut barrier—the layer of cells in the intestine that normally controls which substances can go deeper into the body. The permeability seems to happen when the gut sees a reduction in molecules that normally signal to keep the barrier tightly sealed. But when the barrier is breached, large molecules found in the outer membranes of certain bacteria, called lipopolysaccharide (LPS for short) get past and starts to circulate widely around the body, causing the immune system to release protein messengers that initiate the cascade of reactions leading to inflammation (that is, cytokines). The chronic low-grade inflammation sets off metabolic effects, including disrupted glucose metabolism and fat absorption, with obesity as the end result.
The gut microbial community, which is in proximity to the intestinal barrier, appears to change when the LPS-driven inflammation occurs. Gut microbiota might play a role in kick-starting the whole inflammatory process, or might change only after the process has been initiated. Research is ongoing to try to sort out this cause and effect. It also remains to be seen under what conditions a lifestyle factor (like a high-fat diet) could be enough to set off all of these events in the human body.
As the mechanistic story of obesity unfolds, a major shift in thinking is already warranted. Obesity cannot be explained simplistically as a disease of too many cars, or even too many calories. A group of endocrinologists, in a recent position statement, introduced the term “adiposity-based chronic disease” (ABCD) for obesity, in part to reduce the stigma associated with the word. Yes, lifestyle is important, but we’re starting to see that obesity happens to people, not unlike allergies or Crohn’s disease or arthritis. Gut microbiota could help us understand exactly how.