Manipulating the microbiome

The human micro­biome is one of the most com­plex com­mu­ni­ties of species on the planet. It is the col­lec­tion of all the micro­bial organ­isms in our bodies, the number of which is about 10 times greater than that of our own cells. One day, a better under­standing of the human micro­biome could allow researchers to manip­u­late it for the sake of improved health. How­ever, we cur­rently can’t even dis­cern the roles of indi­vid­uals in a com­mu­nity the frac­tion of its size.

Biology pro­fessor Slava Epstein believes that a better under­standing of much sim­pler com­mu­ni­ties with fewer species could one day inform our under­standing of the human microbiome.

Together with Karen Nelson, director of the J. Craig Ventor Institute’s genomic med­i­cine group, Epstein was recently awarded a three-​​year, $1.5 mil­lion research project funded by the National Sci­ence Foun­da­tion to explore the roles of indi­vidual organ­isms in simple model micro­bial com­mu­ni­ties located in the High Arctic habi­tats of Northern Greenland.

“The holy grail in micro­bial ecology is to figure out the roles of indi­vidual micro­bial species as a com­mu­nity develops,” Epstein said. He explained that sci­en­tists are cur­rently able to use genomics to get a genetic pic­ture of an entire com­mu­nity. The results, how­ever, are lim­ited and frag­mented because they cannot dis­tin­guish one organism’s con­tri­bu­tion from another’s.

With their com­ple­men­tary exper­tise in micro­bial cul­ti­va­tion and genomics, Epstein and Nelson will char­ac­terize the roles of a majority of species in sev­eral simple soil com­mu­ni­ties. First, Epstein’s team will iden­tify the bac­te­rial com­mu­ni­ties they wish to inves­ti­gate, and then they will cul­ti­vate as many species as pos­sible in the lab.

From there, Nelson’s team will ana­lyze each species for genetic, meta­bolic and mol­e­c­ular sig­na­tures to use as ref­er­ences when they look at the com­mu­nity as a whole.

Ulti­mately, they will use the col­lec­tive data to estab­lish com­pu­ta­tional models that can be used to pre­dict out­comes of var­ious envi­ron­mental changes. They will then make the same changes in the wild to verify whether the pre­dicted response is in fact observed. If the model is valid, they will look at larger com­mu­ni­ties, even­tu­ally working toward those as com­plex as the human microbiome.

“If we’re able to increase the abun­dance of one microor­ganism that is ben­e­fi­cial, or decrease the abun­dance of another that is not ben­e­fi­cial,” Epstein said, “this will be a totally dif­ferent universe.”

If pre­dic­tive models work with a simple model com­mu­nity, he said, then larger efforts should work on larger com­mu­ni­ties. He hopes the work will even­tu­ally lead to “smarter” infec­tious dis­ease treat­ments by tar­geting spe­cific organ­isms instead of indis­crim­i­nately wiping out entire com­mu­ni­ties, as is the case with cur­rent antibiotics.

“For now we need to show that the con­cept works in the simple set­ting,” Epstein said.

Provided by Northeastern University