To prescribe the best medicine, it might help if a doctor knows which bacteria live in a patient’s gut. That’s the finding of a new study.
Reports had shown that some gut microbes can alter the drugs that people swallow. That might affect how well those drugs work. But researchers weren’t sure how big a problem this was. Now, a study suggests that gut bacteria can modify many drugs. And that means the genes in those microbes may predict how those drugs would work in that patient.
Maria Zimmermann-Kogadeeva is a computational biologist at Yale University in New Haven, Conn. She and her colleagues shared their new finding June 3 in Nature.
“Knowing how the gut microbes … affect a drug is hugely useful,” says Matthew Redinbo. He did not take part in the new research. But as a biochemist at the University of North Carolina at Chapel Hill, he understands that such effects could help drug companies develop more effective drugs. It could also help doctors choose the best treatment for a particular patient.
Researchers chose 76 types of bacteria that can live in the human gut. Then they tested if — and how — those bacteria changed the molecular structure of 271 drugs. From hormones to anti-virus drugs, each medicine had been designed to be taken by mouth.
The scientists put the bacteria into test tubes holding nutrients and drug solutions. After 12 hours, about two in every three of the drugs had been changed by at least one strain of bacteria. Each of these strains could modify between 11 and 95 different drugs.
“That is huge,” says Nichole Klatt. The microbiome is the sum of all of the microbes living in the body. Klatt is a microbiome researcher at the University of Miami in Florida. She, too, was not involved in the new study. Still, she notes, knowing which microbes affect which drugs isn’t enough. Future studies should look into exactly how bacteria make these changes, she says. Studies might also explore the impacts those altered drugs would have on the human body.
Zimmermann-Kogadeeva and her colleagues wanted to know which part of a bacterium’s DNA lets it modify a particular drug. To find out, they first chopped up DNA from the germs of interest. Then they inserted individual snippets of that DNA into the cells of E. coli bacteria. Afterward, they watched to see which, if any, of these altered E. coli were now able to change the drugs. This told them which DNA fragments could mess with those drugs.
Next, the researchers did a series of tests using different drugs. They started by sampling feces from 28 people. Then they tested whether the community of microbes in each person's poop could modify any of the drugs. In each test, they exposed all the microbial communities to the same drug.
The researchers also scouted in each stool sample for the drug-altering DNA snippets they’d found in the E. coli test. They searched, too, for bits of DNA from other microbes that were at least 50 percent similar to these germs genetically. Their idea was that similar DNA segments likely would do similar jobs.
Feces with more of the drug-altering DNA pieces made more changes to drugs, the team found. That suggests doctors could genetically test a patients’ poop before prescribing them medicine. Such stool tests might tell them whether a patient’s gut microbes would likely alter a drug they could be prescribed.
Such tests might one day help doctors choose which medicine to prescribe. Or doctors might prescribe a treatment that makes a person’s gut microbes friendlier to a certain drug. Antibiotics or fecal transplants might even become ways to change a patient’s gut microbes, says study coauthor Michael Zimmermann. He’s a pharmaceutical scientist and systems biologist at Yale.
But it’s important to consider, too, that the way germs mess with drugs “actually can be beneficial,” Zimmermann-Kogadeeva says. Drug companies might want to make drugs that take advantage of the ability of germs to make a drug work better, she says. Those companies might also design pills to avoid bad reactions with bacteria in the first place.
antibiotic A germ-killing substance, usually prescribed as a medicine (or sometimes as a feed additive to promote the growth of livestock). It does not work against viruses.
bacteria (singular: bacterium) Single-celled organisms. These dwell nearly everywhere on Earth, from the bottom of the sea to inside other living organisms (such as plants and animals). Bacteria are one of the three domains of life on Earth.
biology The study of living things. The scientists who study them are known as biologists.
cell The smallest structural and functional unit of an organism. Typically too small to see with the unaided eye, it consists of a watery fluid surrounded by a membrane or wall. Depending on their size, animals are made of anywhere from thousands to trillions of cells. Most organisms, such as yeasts, molds, bacteria and some algae, are composed of only one cell.
coauthor One of a group (two or more people) who together had prepared a written work, such as a book, report or research paper. Not all coauthors may have contributed equally.
colleague Someone who works with another; a co-worker or team member.
computational Adjective referring to some process that relies on a computer’s analyses.
develop To emerge or come into being, either naturally or through human intervention, such as by manufacturing. (in biology) To grow as an organism from conception through adulthood, often undergoing changes in chemistry, size and sometimes even shape.
DNA (short for deoxyribonucleic acid) A long, double-stranded and spiral-shaped molecule inside most living cells that carries genetic instructions. It is built on a backbone of phosphorus, oxygen, and carbon atoms. In all living things, from plants and animals to microbes, these instructions tell cells which molecules to make.
E. coli (short for Escherichia coli) A common bacterium that researchers often harness to study genetics. Some naturally occurring strains of this microbe cause disease, but many others do not.
fecal transplant A medical procedure that uses bacteria shed in feces (poop) from a healthy person to treat someone who is sick. The bacteria may be delivered down through the mouth and nose (via a tube) or up through the rectum. In some cases, the germs may even be delivered through a capsule that is swallowed. With luck, the new bacteria will colonize the sick patient’s gut — treating the targeted malady.
feces A body's solid waste, made up of undigested food, bacteria and water. The feces of larger animals are sometimes also called dung.
gene (adj. genetic) A segment of DNA that codes, or holds instructions, for a cell’s production of a protein. Offspring inherit genes from their parents. Genes influence how an organism looks and behaves.
germ Any one-celled microorganism, such as a bacterium or fungal species, or a virus particle. Some germs cause disease. Others can promote the health of more complex organisms, including birds and mammals. The health effects of most germs, however, remain unknown.
gut An informal term for the gastrointestinal tract, especially the intestines.
hormone (in zoology and medicine) A chemical produced in a gland and then carried in the bloodstream to another part of the body. Hormones control many important body activities, such as growth. Hormones act by triggering or regulating chemical reactions in the body.
microbe Short for microorganism. A living thing that is too small to see with the unaided eye, including bacteria, some fungi and many other organisms such as amoebas. Most consist of a single cell.
microbiome The scientific term for the entirety of the microorganisms — bacteria, viruses, fungi and more — that take up permanent residence within the body of a human or other animal.
nutrient A vitamin, mineral, fat, carbohydrate or protein that a plant, animal or other organism requires as part of its food in order to survive.
species A group of similar organisms capable of producing offspring that can survive and reproduce.
stool (in medicine) Another name for feces.
strain (in biology) Organisms that belong to the same species that share some small but definable characteristics. For example, biologists breed certain strains of mice that may have a particular susceptibility to disease. Certain bacteria or viruses may develop one or more mutations that turn them into a strain that is immune to the ordinarily lethal effect of one or more drugs.
transplant (in medicine) The replacement of a tissue or an organ with that from another organism. It is also a term for the material that will be transplanted.
virus Tiny infectious particles consisting of RNA or DNA surrounded by protein. Viruses can reproduce only by injecting their genetic material into the cells of living creatures. Although scientists frequently refer to viruses as live or dead, in fact no virus is truly alive. It doesn’t eat like animals do, or make its own food the way plants do. It must hijack the cellular machinery of a living cell in order to survive.