Skip to content

Drugs for bugs: Industry seeks small molecules to target, tweak and tune up our gut microbes

My first encounter with microbiologist Justin Sonnenburg, PhD, came when I was researching "Caution: Do Not Debug," an article I wrote five years ago for Stanford Medicine about the astonishing microbiotic superorganism that beats within the human gut.

According to the Human Microbiome Project, the typical healthy person is inhabited with trillions of intestinal microbes. A person typically hosts 160 or so species of gut bacteria. This bug collection carries its own "shadow genome" consisting of hundreds of times as many genes, in all, than our own measly 20,000 or so human ones.

In exchange for the three square meals a day we provide them, our microbial moochers do lots of good things: From my article:

[O]ur commensal microbes work hard for their living. They synthesize biomolecules that manipulate us in ways that are helpful to both them and us. They produce vitamins, repel pathogens, trigger key aspects of our physiological development, educate our immune system, help us digest our food and for the most part get along so well with us and with one other that we forget they’re there.

Since I wrote that piece, the list of microbial good deeds has continued to grow. As Sonnenburg pointed out recently in a review article in CELL Metabolism, "Starving our Microbial Self," our resident microbes are producing hundreds or thousands of little drug-like compounds. For example: Short-chain fatty acids, generated by our gut bacteria from starches and fiber in our diet, downregulate inflammation.

Quoted in a just-published feature in Nature Biotechnology, "Drugging the Microbiome," Sonnenburg elaborates:

Might a lack of dietary fiber lead directly to autoimmune and inflammatory diseases? That's the view of Justin Sonnenburg, a Stanford microbiologist. “A reduction in short-chain fatty acid production... is what happens when you get rid of dietary fiber, and [leads to] increasing inflammatory responses of the host immune system,” he says. “And it's this simmering state of inflammation that the Western immune system exists in that's really the cause of all the diseases that we've been talking about. ... You can just imagine that if you get rid of these important regulatory molecules, and the immune system becomes a little bit pro-inflammatory across a large population, you're going to see increases in things like cancer, heart disease, allergies, asthma and inflammatory bowel disease.”

While they're indispensable, our gut microbes can do bad things, too. Research has implicated them in the production of certain metabolites implicated in deleterious effects, with potential involvement in conditions ranging from heart disease to autism to Parkinson's to colon and liver cancer, according to the Nature Biotechnology feature.

Either way, it's going to be well worth our while to learn everything we can about the details of the ecosystem of one-celled creatures who call us "home."

Previously: Civilization and its dietary (dis) contents: Do modern diets starve out our gut-microbial community?, The future of probiotics and Researchers manipulate microbes in the gut
Photo by Duncan Hull

Popular posts

Category:
Biomedical research
Stanford immunologist pushes field to shift its research focus from mice to humans

Much of what we know about the immune system comes from experiments conducted on mice.  But lab mice are not little human beings. The two species are separated by both physiology and  lifestyles. Stanford immunologist Mark Davis is calling on his colleagues to shift their research focus to people.