Mi­crobes En­er­gize the Brain 

Note­wor­thy

Hu­mans are dif­fer­ent from other pri­mates due to a com­bi­na­tion of fea­tures. Prime among these is the large brain size that en­dows us with a dis­tinct ca­pac­ity for com­plex rea­son­ing, plan­ning, and de­ci­sion-mak­ing. But a large brain size de­mands a lot of en­ergy. Could mem­bers of the gut mi­cro­biota have co-evolved to sup­port this high de­mand for glu­cose in our brains? 

This is the ques­tion ad­dressed in a re­cent study by re­searchers from var­i­ous in­sti­tu­tions in the US. The gut mi­cro­biota is known, af­ter all, to in­flu­ence brain ac­tiv­ity by its con­nec­tion via the gut-brain axis. To un­der­stand whether pri­mate brain evo­lu­tion could have been in­flu­enced by mi­crobes in the gut, the au­thors in­oc­u­lated germ-free mice with the gut mi­cro­biota from three pri­mate species with dif­fer­ent brain sizes – hu­mans, macaques, and squir­rel mon­keys. In a pre­vi­ous study, this group had shown that trans­fer­ring gut mi­crobes from pri­mates into mice in­flu­enced host en­ergy me­tab­o­lism.

Hu­man and mon­key gut mi­cro­biota (GM) drive di­ver­gent gene ex­pres­sion in mouse brains. Car­toons and ar­rows sum­ma­rize ex­per­i­ments and analy­ses re­ported in the study. Dou­ble-headed ar­rows rep­re­sent dif­fer­en­tial gene ex­pres­sion be­tween host groups, in­clud­ing hu­mans, non-hu­man pri­mates (NHPs), and germ-free (gno­to­bi­otic) mice. Sin­gle-headed ar­rows rep­re­sent fe­cal-mi­cro­biota trans­plan­ta­tion. Source. Fron­tispiece: Hu­man and macaque brains com­pared, mod­i­fied from source.

In this new study, the con­nec­tion be­tween gut mi­crobes and the brain be­came ev­i­dent. Their ap­proach in­volved the analy­sis of gene ex­pres­sion in the frontal cor­tex, the part of the brain re­spon­si­ble for high-level cog­ni­tive func­tions, such as de­ci­sion-mak­ing, plan­ning, and  prob­lem-solv­ing. Frontal cor­tex gene ex­pres­sion pat­terns in mice brains with trans­planted mi­cro­biota looked sim­i­lar to those in the orig­i­nal pri­mate hosts. But even more in­ter­est­ing was the fact that the hu­man gut mi­cro­biota in­creased the ex­pres­sion of genes as­so­ci­ated with en­ergy pro­duc­tion and use in the brain, and down­reg­u­lated some genes in­volved in neu­rode­vel­op­men­tal dis­or­ders. 

Al­though this study was lim­ited to sam­ples from just three pri­mate species, it does sug­gest that gut mi­crobes can rewire the brain. The ob­served ef­fects also hint at a pos­si­ble co-evo­lu­tion of gut mi­crobes to sup­port the en­er­getic de­mands of larger brains, an in­trigu­ing hy­poth­e­sis that will need fur­ther test­ing.