All animals harbor legions of bacteria in their guts that aid in digestion. Now research with tiny, transparent zebrafish suggests that some of these bugs do more: altering the activity of individual genes in their host, and potentially shaping the fish's development and physiology.
Previous experiments with mice revealed that bacteria influence their hosts' immunity, digestion, and other functions. But it was difficult to tease out the chemical signals the bugs use. To investigate, microbiologist John Rawls and colleagues in Jeffrey Gordon's lab at Washington University School of Medicine in St. Louis, Missouri, turned to the zebrafish, which remains transparent until it reaches an adult length of about 1 to 2 centimeters. The researchers raised zebrafish bereft of all bacteria and compared them to zebrafish raised normally.
Similar to their previous findings in germ-free mice, the new results showed that the immune system failed to fully develop in bacteria-deprived fish, which also had diminished abilities to process nutrients and regenerate their intestinal linings. More than 200 genes in the germ-free zebrafish showed levels of activity different than those in their bacteria-exposed cousins. Surprisingly, the team also found 66 genes analogous to ones regulated by beneficial bacteria in the mouse intestine--suggesting that some host-bacterial interactions derive from an ancient ancestor of both mice and fish.
Adding normal gut bacteria back to the germ-free zebrafish species by species revealed that some changes in gene expression were specific to certain types of bacteria, they report online this week in the Proceedings of the National Academy of Sciences. The researchers hope that identifying chemicals produced by the bacteria will help explain how the bugs interact with their hosts.
In raising the first germ-free zebrafish, the team has produced "extremely powerful tools for examining the influence of beneficial bacteria on animal development," says microbiologist Margaret McFall-Hgai of Kewalo Marine Laboratory in Honolulu, Hawaii. The zebrafish's transparency, small size, and rapid reproduction make it one of the best models for studying how animals and bacteria "talk" to each other, she adds.