This article first, appeared in the St. Louis Beacon, May 13, 2009 - Are microbes making Americans fatter?
The number of overweight and obese people in the United States is skyrocketing. Thirty-five years ago, about 47 percent of adults were considered overweight, with 15 percent of them being obese. By 2008, those statistics increased to 76 percent of the population being overweight with 32 percent of them tipping the scales to obesity.
The 35-year trend is the same in children and adolescents, with an increase in overweight children (6-11 years of age) from 7 percent of the population to 19 percent and an increase in overweight adolescents (12-19 years old) from 5 percent to 17 percent.
What is fueling this trend?
Like detectives at the scene of a crime, scientists have looked for clues, starting with the usual suspects: genes and behavior. Right off the bat, researchers suspected a genetic contribution, as obesity tends to run in families. But family members also share similar diets and lifestyles, making it hard to dissect behavioral factors from the genetic ones.
One genetic mutation that has been linked to obesity in mice, dubbed the obese gene (ob), is also found in humans. This gene encodes a protein hormone called leptin. A mutation in this gene (or, in the gene that encodes its receptor) results in a lack of leptin response in mice, leading to obesity. But mutations in this genes appear to be very rare in humans, so ob could not be a significant factor in the increases we are seeing in obesity.
Besides, the genetic composition of our countries population just could not change that rapidly in a single generation. Something "nongenetic" is at work here.
What else might be fueling this trend to obesity? It doesn't take a scientist to hypothesize that a change in lifestyle is contributing to an increase in weight. Today's "super-size it" fast-foods, "big gulp" drinks and "all-you-can-eat" buffets, coupled with lack of physical exercise, leaves Americans consuming more and more calories without the physical activity needed to burn off those calories. Drive-through windows mean we don't even have to get out of our cars and walk to get our high-calorie food!
A high-calorie, low-exercise lifestyle is certainly a major contributor to the obesity epidemic we are experiencing -- although, as we shall see, probably not the only one.
Scientists have recently stumbled over a third potential cause of today's obesity outbreak, a cause both unexpected and surprising. The culprit? Micro-organisms that live in your gut.
This story starts with a different type of investigation, that of nutritionists exploring what people eat. After you eat, the job of your digestive system is to break down food and extract nutrients and energy from it. As food passes through the stomach and small intestine it is broken down by chemicals and enzymes and absorbed by the body.
We can monitor what we take into our bodies by reading the nutritional labels on food packages. These labels will list the nutritional benefits of the food, for example, a bowl of cereal with skim milk may contain 150 calories with 1.5 grams of fat, 315 mg of sodium, 115 mg of potassium, 34 g of carbohydrates, 11 g of protein and numerous vitamins and minerals. It was always assumed that this bowl of cereal offered the same nutritional value, whether the consumer was thin or overweight. But researchers are now finding that might not be the case.
The human digestive system is teeming with 10 trillion to 100 trillion micro-organisms, primarily bacteria. These bacteria outnumber the cells in the human body by at least 10 times. In this sense, we are more microbe than human!
This is a symbiotic microbe-human relationship, with both partners benefiting. The bacteria have a moist, warm place to live, and ample food. The human host also benefits because the bacteria inhibit the invasion of disease-causing relatives that could make the host sick. Even more importantly, they help in the digestion of the food you eat. The bacteria in your gut have certain digestive enzymes that your body lacks, which allows them to break down food products that would otherwise pass through your body as indigestible waste. When the bacteria break down this food, much of the extra energy and nutrients become available to you, added bang for your food buck.
None of this is news. Scientists have known about these beneficial bacterial inhabitants for a long time. What they didn't know was that the mix of intestinal bacteria in all humans is not the same.
Dr. Jeffrey Gordon of the Washington University School of Medicine and colleagues found that although humans can harbor thousands of different types of intestinal microbes, almost all (more than 90 percent) are bacteria that belong to one of two groups, the Firmicutes (an example is shown in the photo of Lactobacillus) and the Bacteriodetes (an example in the photo of Bacteroidetes).
Now comes the interesting bit: unexpectedly, the distribution of these two groups is different in obese people compared to their leaner counterparts. Of the volunteers in this study, obese people had a higher proportion of Firmicutes than lean people did, with the lean patients having a higher proportion of Bacteriodetes.
While this is an interesting observation, it might, in principle, be a result of factors other than just weight. To test this possibility, these obese patients were put on diets (both low-fat and low-carbohydrate diets) to lose weight. Did the mix of microbes change? Yes. The balance of the two kinds of bacteria in their guts changed to reflect more closely that of lean patients, showing decreases in the proportion of Firmicutes and increases in Bacteriodetes.
What role might host genes play?
To look into this, the study also examined the intestinal microbes of genetically obese mice (ob/ob mice recessive for the obese gene). Like humans, genetically obese mice also contain a higher proportion of Firmicutes in their guts, while the guts of normal lean mice are dominated by the Bacteriodetes. But are the Firmicutes bacteria in genetically obese mice a cause or result of obesity?
To address this very key question, the investigators "infected" the guts of germ-free mice (mice that have never been exposed to bacteria) with microbial samples taken from the intestines of lean and obese mice. Both experimental groups gained weight, but the mice that received bacteria from the obese donors gained significantly more weight without increases in food consumption.
The mice with the "obese" bacteria gained weight not because they ate more food, but because they extracted more energy from their food.
How could the Firmicutes affect how much energy is extracted from the food that is eaten? Apparently the Firmicute bacteria living in higher proportions in obese mice are more efficient at breaking down complex polysaccharides (long-chain carbohydrates that are more difficult to digest) into simple sugars such as glucose. This additional glucose is then available for energy use by muscles and, if this energy is not used in exercise and other activity, it is stored in the body as fat.
So, what happens to a bowl of cereal eaten by an obese person compared to a lean person? When people, fat or thin, eat a bowl of cereal, their body produces enzymes such as pepsin, trypsin and chymotrypsin that break down proteins; sucrase and amylase that break down carbohydrates; bile and lipase that break down fats. But, when this person sits down to a meal, he or she never dines alone. The trillions of bacteria that live in their digestive systems also enjoy the feast.
Does a human need these bacteria to live? The studies involving germ-free mice suggest that these bacteria are not necessary for life. Germ-free mice that contain no bacteria in their guts are able to survive; their bodies alone are able to digest enough food to sustain themselves. But, by adding microbes to their digestive systems they gain more weight, and this is true whether the added bacteria are predominately obese (Firmicutes) or lean (Bacteriodetes). This means that both kinds of gastrointestinal bacteria improve the efficiency of the digestive system.
Apparently both kinds of bacteria fail to consume all of the products of their digestion, leaving "left overs" to be absorbed by the host. In this way, the germfree mice gain weight when infected with either kind of intestinal bacteria.
This is not the end of the story. Researchers who compared digestion in germ-free mice and normal mice found that the gut microbes in normal mice were manipulating their host's metabolism.
The microbes suppressed the production of a substance in the host called fasting-induced adipose factor (Fiaf). The function of Fiaf in the body is to keep fat cells from storing fat. By suppressing Fiaf, the "gates" to the fat cells stay open and store more fat. The microbes also lowered the levels of another protein in the body that stimulates breaking down fat stores. So, the microbes not only digest more food for the host to absorb, they also encourage the body to store more of that food as fat and work to keep that fat on.
The two kinds of intestinal bacteria are not equal in this process. Firmicutes bacteria that are present in a higher proportion in the guts of obese mice and people suppress Fiaf more effectively, and also are more efficient at breaking down polysaccharides, making more sugar available for absorption by the host. Fast-food diets and lack of exercise will make anyone overweight, but Firmicutes intestinal microbes appear to accelerate the process.
It would seem we are not only what we eat, but also who helps us eat it.
George B. Johnson's "On Science" column looks at scientific issues and explains them in an accessible manner.
Johnson, Ph.D., professor emeritus of Biology at Washington University, has taught biology and genetics to undergraduates for more than 30 years. Also professor of genetics at Washington University’s School of Medicine, Johnson is a student of population genetics and evolution, renowned for his pioneering studies of genetic variability. He has authored more than 50 scientific publications and seven texts.
As the founding director of The Living World, the education center at the St Louis Zoo, from 1987 to 1990, he was responsible for developing innovative high-tech exhibits and new educational programs.