Out on the cutting edge of biology lies talk of manipulating our gut microbiome. This sounds like a bold idea, but it looks like we may already be hacking our microbiomes without even realizing it. A new paper from Shirong Liu in Howard Weiner’s lab at Harvard suggests that our gut cells have already figured out how to control bacteria inside us using miRNAs.
Gut Cells Release miRNAs
We know that fecal miRNAs can be biomarkers for disease. To see if miRNAs are in there normally, the Harvard team sampled both human and mouse droppings, in both of which they found butt-loads of miRNAs (we couldn’t resist):
- The miRNA profile was different in different parts of the intestine and there were more miRNAs overall in the ileum than the colon.
- Mice that were germ-free or antibiotic-treated had more fecal miRNAs, but mice with DSS-induced colitis, which kills off intestinal epithelial cells, had fewer.
To sniff out the source of these particularly malodorous miRNAs, the team knocked out Dicer1, which is necessary to make miRNAs, in various mouse cell types. When they blocked miRNA production in either intestinal epithelial cells or Hopx+ cells, miRNA levels dropped.
Gut miRNAs Are Hacking The Microbiome
miRNAs in the gut are interesting, but not all that surprising. The real surprise came when the team looked at mice with no Dicer (and thus fewer miRNAs) in their gut cells – these mice had more diverse gut flora. Impressively, transplanting purified miRNAs from wild type mouse poop into the miRNA-challenged mice reduced gut diversity back toward normal!
miRNAs affect gene expression in eukaryotes, so the team checked if any of these miRNAs had potential binding sites in bacterial genomes, and indeed they did:
- Testing two bacteria with predicted miRNA targets showed that both species grow better when mixed with those miRNAs, but scrambled versions had no effect.
- When the team labeled miRNAs with cy3, both bacteria sucked in the dye, showing that miRNAs really do get inside them.
- What’s more, miRNAs clearly changed expression of their predicted target genes.
- In an impressively elegant intervention, the team added E. coli growth-enhancing miRNAs to mouse drinking water, and the miRNAs increased E. coli inside the mice.
So secreted miRNAs change the microbiome, but does this have any effect on health? To test this, the team went back to mice with DSS-induced colitis. Those that couldn’t make miRNAs in their guts had worse symptoms, but simply transplanting miRNAs – not bacteria – from wild type mice made the colitis significantly better.
Wait But What About…
This study revealed a whole new interaction between host and microbiome, which opens up a new realm of questions. For example:
- What form of gut miRNAs are most important – free floating, inside extracellular vesicles, or other?
- How do miRNAs get inside bacteria?
- How do miRNAs change bacterial gene expression?
Despite the new questions begging for answers, this study shows that animals can and do manipulate the bacteria inside them on the genetic level. Perhaps the most exciting find is that simply putting miRNAs in drinking water can change gut bacteria. Since miRNAs are relatively cheap, and we keep finding more health effects of gut bacteria every day, this could lead to a simple daily microbiome shake, if we can figure out the right miRNAs to cultivate the right bacteria.
Wash your hands, then go check out the paper at Cell Host & Microbe, 2016.