Researchers studying mutually beneficial interactions between members of our vast community of friendly gut microorganisms have shown that two common organisms collaborate to increase the amount of calories harvested from a class of carbohydrates found in food sweeteners.
In the study, conducted in previously germ-free mice, colonization with two prominent human gut microbes led to fatter mice. School of Medicine scientists called the results an illustration of how understanding the menagerie of microorganisms that live in our guts can provide new insights into health.
The study was published online by the Proceedings of the National Academy of Sciences.
To one day consider manipulating gut microbes for medical benefits, such as weight loss or gain, scientists need to know what kind of microbes are living in our digestive systems and how they form strategic alliances with one another to benefit themselves and us. They also have to learn how much this cast of microbial characters varies in different human individuals.
“We are superorganisms containing a mixture of not just human cells but also bacterial cells and cells of another microscopic domain of life known as Archaea,” said senior author Jeffrey Gordon, M.D., the Dr. Robert J. Glaser Distinguished University Professor. “As adults, the number of these bacterial and archaeal microbial cells exceeds the number of our human cells by tenfold. The genes present in this community of 10-100 trillion bugs vastly outnumber our own genes and are a key part of our genetic landscape, providing us with attributes we have not had to evolve on our own.”
One such attribute is the ability to digest commonly consumed complex sugars known as polysaccharides. Many types of polysaccharides pass through the small intestine mostly unchanged because our human genome does not have the genes needed to digest them. Bacterial partners living in our colons, such as Bacteroides thetaiotaomicron, begin a fermentation process that breaks down these nutrients so that the stored calories can be liberated and absorbed.
But B. thetaiotaomicron doesn’t just work in a simple partnership with its host. The human gut contains hundreds, and perhaps thousands, of different microbial species, and the functions they perform affect each other and their hosts.
Gordon’s lab models the interactions between friendly gut microbes and their hosts using gnotobiotic mice. These mice are raised in a manner that keeps them germ-free. They are then colonized with one or more human gut-derived microbes to study how microbial-microbial and microbial-host interactions affect digestive health.
Buck Samuel, a doctoral student in Gordon’s lab, began to probe the influence of Methanobrevibacter smithii, an archaeon. Originally identified in the 1970s and mistaken for a primitive form of bacteria, archaea initially became famous because of their ability to live in extreme environments where nothing else could survive, such as hot springs.
Scientists first isolated archaea from the human intestine in 1982, and have recently recognized M. smithii as the most common archaeon in human intestines.
In addition to its prevalence, M. smithii was an intriguing target for study because of its ability to consume hydrogen and other byproducts of bacterial digestion of polysaccharides. Accumulation of such byproducts slows polysaccharide digestion.
Samuel and Gordon speculated that M. smithii could improve the overall efficiency of digestion of dietary polysaccharides, and wondered whether it also affected which types of polysaccharides are most coveted by intestinal bacteria.
Samuel colonized one group of gnotobiotic mice with the polysaccharide-digesting bacterium B. thetaiotaomicron. Another group was colonized with M. smithii, while a third group received both B. thetaiotaomicron and M. smithii.
The archaeon’s presence dramatically affected gene activity in B. thetaiotaomicron, shifting its appetite to a more abundant class of polysaccharides known as fructans. Commonly found in Western diet, fructans are used as food sweeteners. This taste change increased B. thetaiotaomicron‘s ability to produce energy for itself, and to make energy available in forms that the mouse could absorb and use.
The result was that mice colonized with both organisms had significantly more fat than animals colonized with either microbe alone. Thanks to B. thetaioatomicron, M. smithii also benefited by receiving increased amounts of formate, a product of polysaccharide fermentation that it uses.
“The presence of M. smithii improved the overall efficiency of the digestive system,” Gordon said. “It remains to be established whether we can intentionally manipulate this gut archaeon to improve digestive health. It will also be interesting to see if levels of M. smithii in the gut microbial community vary in obese versus lean individuals.”