September 12, 2012 | 7
There’s a food fight in your guts. Not the Tater-Tot-chucking, spoonful-of-mashed potato-flinging, melee-in-the-cafeteria type of food fight. Rather, your intestines are the site of an ancient and complex war between your own cells and trillions of bacteria—a war over what happens to your food as it moves through your body. Some of the bacteria form genuine alliances with your intestinal cells, breaking down tough plant fibers that your cells cannot handle on their own, or chopping up lengthy caterpillar molecules into more digestible packages, in exchange for a portion of the day’s calories. Other bacteria lurk and loiter, sipping the nutrient-rich broth sloshing in your intestines as they wait for their chance to overrun your guts at the expense of your health. Every day, these microorganisms squabble amongst themselves for greater access to available nutrients. And sometimes your cells fight back, working extra hard to digest the food you eat before those persistent microbes help themselves to a disproportionately large serving. Studies suggest that the diversity of bacterial species in our guts partially determines how efficiently our cells process and store food and that, in a feedback loop, what we eat alters the demographics of the bacteria in our intestines. Commonly prescribed antibiotics are responsible for unintended microbial casualties, further changing how our resident population of microorganisms responds to our diet. Although scientists are still figuring out the rules of this intricate food fight, it’s evident by now that our guts are not entirely our own—they are composite organs, part-human, part-microbe, which evolved, and continue to function, as communities whose many minute members are sometimes cooperative, sometimes combative and always hungry.
A study published this week adds nuance to scientists’ evolving understanding of how gut bacteria change the way animals digest food. Ivana Semova and John Rawls of the University of North Carolina at Chapel Hill, along with their colleagues, studied the absorption of fluorescent fatty acids in the intestines of tiny translucent zebrafish (Danio rerio). Compared to zebrafish raised in germ-free environments, zebrafish whose guts were colonized by bacteria absorbed more fat from their diets. And the more the fish ate, the larger the population of bacteria in their guts. In particular, eating encouraged the growth of a tribe of bacteria known as Firmicutes, which in turn increased the number of energy-rich fat bubbles stored within the fish’s intestinal cells for later use. Studies with people and mice have also shown that high-calorie diets stimulate the growth of Firmicutes in the gut, hinting that this particular group of bacteria may respond to its host’s diet in similar ways across many different species. What remains unclear is whether Firmicutes helps animals absorb more calories from their food in a mutually beneficial partnership or if the relationship is more complex—and sometimes less than benevolent.
Bacteria constitute between 40 and 60 percent of the dry weight of human feces, with trillions of cells in every gram. Zebrafish intestines are not home to the exact same species of bacteria that live in our own guts, but—if you take a broad enough view of the communities—they have a surprising amount of overlap. Both communities are dominated by the phyla Proteobacteria, Firmicutes, and Bacteroidetes (phylum is the taxonomic level below kingdom). Young zebrafish are also particularly convenient for scientists who want an inside look on the digestive process because day-old zebrafish are transparent—you you can see everything that is happening in their intestines under a microscope without the need for a damaging and disruptive dissection.
Semova and Rawls chemically bonded fluorescent molecules to two common fatty acids, palmitic acid pentanoic acid, and mixed the glowing fats into the egg yolk of embryonic zebrafish. The intestinal cells of zebrafish that were exposed to bacteria as they developed glowed more brightly than the intestinal cells of zebrafish that were raised in sterile environments, indicating that zebrafish guts squirming with bacteria absorbed more fat. The intestinal cells of zebrafish with healthy populations of gut bacteria, collectively known as gut microbiota, also contained larger lipid droplets—bubbles of fat stored as expedient sources of energy.
The number of lipid droplets in the fish’s intestinal cells depended on their diet. Fish with bacteria in their guts and a steady source of food had much higher numbers of lipid droplets in their intestinal cells than fish that were denied food for a few days. Eating specifically promoted the growth of bacterial species in the phylum Firmicutes and this increase was not reflected by changes in the numbers of bacteria in the surrounding water. Eating changes a fish’s internal ecosystem. The more a zebrafish eats, the more Firmicutes in its guts. And the more Firmicutes in a zebrafish’s guts, the more efficiently its intestinal cells absorb fat.
To investigate how Firmicutes stimulates fat absorption, Semova and Rawls grew different strains of bacteria in different liquid media, which you can think of as a kind of broth. After filtering out the bacteria, they exposed baby zebrafish to the different media. Only media from Firmicutes significantly increased the number of lipid droplets in the fish’s intestinal cells, suggesting that whatever proteins or molecules those bacteria secreted into the media somehow enhanced fatty acid absorption. The results were published September 13 in Gut Host & Microbe.
These findings mirror the conclusions of many previous studies, which have shown, for example, that starving mice for a single day reduces the population of Firmicutes in their guts and that transplanting Firmicutes from obese mice into the germ-free intestines of lean mice makes the thin rodents plump. When obese people begin a low-fat or low-carb diet, Bacteroidetes proliferates and Firmicutes dwindles. Clearly, Firmicutes is happiest when we are eating a lot. One pertinent and unanswered question is whether we should share that happiness. Are Firmicutes graciously helping us extract more calories from our food, taking only a modest cut for themselves? Are they selfishly increasing their own numbers when the eating is good, forcing our cells to sweat to get the most out of our food? Are they in fact making digestion too easy, liberating so many calories from our food that we absorb far more than we need? Perhaps there is truth in all these scenarios.
“We are in the midst of a revolution of our ability to describe the composition and physiological potential of these bacterial communities,” Rawls says. “What we can begin to speculate on, though, are the different types of relationships that might be taking place. We know gut microbiota enhance our ability to extract calories from complex carbohydrates, which is clearly a mutually beneficial relationship. But it’s thought that all vertebrates have the capacity to digest and absorb other types of nutrients, such as lipids, proteins and simple carbohydrates, so it’s not readily clear how we could enter into a mutually beneficial relationship with bacteria with regard to those nutrients. When we see fatty acid absorption increased in zebrafish, that may be selfish or defensive response. Perhaps the fish recognizes the presence of more bacteria and increases its own fatty acid absorption. It may not always be such a friendly arrangement.”