Resident Microbes Restructure Body Chemistry

Microbiomes – the community of microorganisms such as bacteria, virus, and fungi that dwell in and on the human body – have been shown to influence everything from our athleticism to predisposition to the disease.

According to the paper published in the journal Nature, these microbes control the structure of bile acids and strongly simulate a specific gut receptors called farnesoid X, thereby changing everything from how cells communicate to one another to how genes express.

Bile acids are a family of molecules which are synthesized in the liver. They facilitate digestion of fats and oils, and carry information from the gut to other parts of the body, which is accomplished through the use of farnesoid X receptors.

“We hear a lot about how our own human genes influence our health and behaviors, so it may come as a shock to think that we could have molecules in the body that look and act the way they do not because of our genes, but because of another living organism,” explained Pieter Dorrestein of the UC San Diego, the lead author of the paper.

This action of microbes, for sure, can cripple our immunological defense mechanism. But how exactly such tiny organisms play such an authoritative figure in altering body chemistry of a human being?

To find out, a team of researchers at the University of California San Diego turned to a mouse model and create the first-ever map of all the molecules in every organ. They also laid out the ways in which how microbes restructure those molecules.

They started off by comparing germ-free (sterile) mice and mice with normal microbes. Then using mass spectrometry, they characterized and identified as many as non-living molecules in each organ as possible by benchmarking them with the structures in the GNPS database. They also located the microbes that cohabitate with these molecules and determined them via genetic sequencing.

768 samples from 96 sites of 29 organs from four germ-free mice and four mice with normal microbes were analyzed in total. The upshot of that assessment was a map of all of the molecules found in the body of a normal mouse with microbes, and that of molecules throughout a mouse free of microbes.

Then upon comparing the maps, the team found that as much as 70 percent of a mouse’s gut chemistry is regulated by its gut microbiome. 20 percent of molecules in organs that lie far from the gut, such as the uterus or the brain, were revealed to be different in the mice with microbes present.

They also discovered that the structure of bile acids remains unscathed in the case of sterile mice. However, in the case of mice with normal microbiomes, the molecules are inordinately restructured, and are tagged with amino acids such as phenylalanine, tyrosine and leucine instead of being conjugated (by enzymes in the liver) with amino acids, such as glycine and taurine.

“More than 42,000 research papers have been published about bile acids over the course of 170 years,” said Robert Quinn of Michigan State University. “And yet these modifications had been overlooked.”

Well, are these types of microbe-modified bile acids found in humans, too? Yes, of course.

To make sure, the team used the Mass Spectrometry Search Tool (MASST) and looked for 1,004 public datasets of specimens analyzed with mass spectrometry. Mass spectrometry analysis of 3000 stool samples was also carried out.

The result: 25.3 percent of all human samples in the datasets match that of the unique microbial-modified bile acids found in mice. Also, as the researchers pointed out, these novel bile acids were predominantly found in infants and patients with inflammatory bowel disease or cystic fibrosis.

As has been stated, bile acids leverage farnesoid X receptor to deliver messages from the gut to other parts of the body. They also bind and activate the said receptors, then shut off production of more bile acids by blocking genes responsible for it. Farnesoid X receptors also help optimize the levels of liver triglyceride and fluid regulation in the intestines, making them useful in curbing progression of liver disease and possibly obesity.

So it’s fairly certain to say that, in the lab-grown mice and human cells , bile acids that have been tempered by microbes strongly stimulate farnesoid X receptors, reducing expression of genes responsible for bile acid production in the liver.

“This study provides a clear example of how microbes can influence the expression of human genes,” Dorrestein said. “What we still don’t know is the downstream consequences this could have, or how we might be able to intervene to improve human health.”

The result of the study is freakishly astonishing, especially considering the extent of influences such tiny organisms have on a human. We are literally shaped by resident microbes.