Turning the gut microbiome into a chat room

Altering how bacteria talk to each other can change the balance of microbes in the body, a new study suggests.

By butting in to bacterial conversations, friendly microbes may better resist the ravages of antibiotics, researchers report online March 19 in Cell Reports. Treating mice with antibiotics depleted the number of one major group of bacteria called Firmicutes naturally found in the gut. But boosting levels of a communication molecule slightly altered the microbial mix in the intestines, restoring a fraction of the Firmicutes population, the researchers found.

Manipulating bacterial communication might eventually help researchers reshape microbial mixes in people whose friendly bacteria have been discombobulated by antibiotics or disease. “It adds to the repertoire of tools that can be used,” says Willem M. de Vos, a microbiologist at Wageningen University in the Netherlands and Helsinki University in Finland. He was not involved in the study.

Researchers have assumed that bacteria in the intestines, often called the gut microbiome, talk to each other using a communication molecule called autoinducer-2 or AI-2 for short, says Anisa Ismail, an immunologist and microbiologist at Princeton University. Until now, that assumption has had little supporting evidence.

AI-2 is a chemical produced by many types of bacteria to count each other and determine when a large enough population, a quorum, has been reached to carry out certain activities. This “quorum sensing” molecule “is the Esperanto among the bacteria,” says Johannes Hübner, a clinical microbiologist at the Medical Center of the University of Munich. “It’s the only language they have in common.” 

In the new study, researchers led by Karina de Bivar Xavier of the Instituto Gulbenkian de Ciência in Oeiras, Portugal, treated mice with an antibiotic called streptomycin. Before the antibiotic, the mice had a gut microbial mix that was 43 percent Firmicutes and 48 percent Bacteroidetes. The ratio of those major groups of bacteria has been shown to be important for health.

After 28 days on the antibiotic, the Bacteroidetes group made up about 90 percent of the gut microbiome, while the Firmicutes had dwindled to 0.7 percent. Xavier’s team wanted to see if altering communication between bacteria could shift the microbiome toward a healthier mix.

The team made E. coli strains that either increased levels of AI-2 in the intestines or sponged it up and lowered the concentrations. Sucking away the chemical messenger made things even worse for the Firmicutes. Those bacteria made up only 0.13 to 0.24 percent of the gut microbes in antibiotic-treated mice also infected with AI-2–sponging E. coli. But E. coli that raise levels of the quorum sensing molecule boosted Firmicutes to 0.8 percent of the population. In contrast, one type of Bacteroidetes bacterium was abundant in mice with low levels of AI-2, making up 20.5 percent of the gut microbiome. But in mice with high levels of the communication chemical, those bacteria made up only 7.3 percent of the gut microbes.

The results indicate that quorum sensing can influence the microbiome, but the researchers don’t know the mechanism yet.

The shift is far too subtle for any therapies to be based on the findings, says Michael Otto, a molecular microbiologist at the National Institute of Allergy and Infectious Diseases in Bethesda, Md. He’s also not convinced that the changes are due to altering the chemical conversation. Researchers have debated whether Firmicutes and related bacteria actually use quorum sensing to talk to each other, or merely use the quorum sensing chemical as food. “Whether this whole thing is really quorum sensing … is not clear,” Otto says.

Also unclear is whether only helpful species of bacteria are increasing in number, says Hübner. His group has evidence that sending quorum signals to pathogenic bacteria can make them more dangerous.