The human body is full of tiny microorganisms -- hundreds to thousands of species of bacteria collectively called the microbiome, which are believed to contribute to a healthy existence. The gastrointestinal (GI) tract¹ -- and the colon² in particular -- is home to the largest concentration and highest diversity of bacterial³ species. But how do these organisms persist and thrive in a system that is constantly in flux⁴（在变化） due to foods and fluids moving through it? A team led by California Institute of Technology (Caltech) biologist Sarkis Mazmanian believes it has found the answer, at least in one common group of bacteria: a set of genes⁵ that promotes stable microbial colonization⁶ of the gut⁷. A study describing the researchers' findings was published as an advance online publication of the journal Nature on August 18.

 

"By understanding how these microbes colonize⁸, we may someday be able to devise（设计） ways to correct for abnormal changes in bacterial communities -- changes that are thought to be connected to disorders⁹ like obesity¹⁰, inflammatory bowel¹¹ disease and autism," says Mazmanian, a professor of biology at Caltech whose work explores the link between human gut bacteria and health.

 

The researchers began their study by running a series of experiments to introduce a genus of microbes called Bacteriodes to sterile¹², or germ-free, mice. Bacteriodes, a group of bacteria that has several dozen species, was chosen because it is one of the most abundant genuses in the human microbiome, can be cultured in the lab (unlike most gut bacteria), and can be genetically¹⁴ modified to introduce specific mutations.

 

"Bacteriodes are the only genus in the microbiome that fit these three criteria," Mazmanian says.

 

Lead author S. Melanie Lee (PhD '13), who was an MD/PhD student in Mazmanian's lab at the time of the research, first added a few different species of the bacteria to one mouse to see if they would compete with each other to colonize the gut. They appeared to peacefully coexist. Then, Lee colonized¹⁵ a mouse with one particular species, Bacteroides fragilis, and inoculated¹⁶ the mouse with the same exact species, to see if they would co-colonize the same host. To the researchers' surprise, the newly introduced bacteria could not maintain residence in the mouse's gut, despite the fact that the animal was already populated by the identical species.

 

"We know that this environment can house hundreds of species, so why the competition within the same species?" Lee says. "There certainly isn't a lack of space or nutrients¹⁷, but this was an extremely robust¹⁸ and consistent finding when we tried to essentially¹⁹ 'super-colonize' the mice with one species."

 

To explain the results, Lee and the team developed what they called the "saturable²⁰ niche²¹ hypothesis." The idea is that by saturating²² a specific habitat, the organism will effectively exclude others of the same species from occupying that niche. It will not, however, prevent other closely related species from colonizing²³ the gut, because they have their own particular niches²⁴. A genetic¹³ screen revealed a set of previously²⁵ uncharacterized genes -- a system that the researchers dubbed²⁶ commensal colonization factors (CCF) -- that were both required and sufficient for species-specific colonization by B. fragilis.

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