The genes of the beneficial bacterial species Lactoplantibacillus (red) enable it to attach to a specific niche in the fruit fly gut (blue/cyan)
Beneficial bacteria occupy specific regions in the gut, contributing to our health via the microbiome. A new study has identified the genes that good bacteria use to colonize these regions, opening the door to creating engineered probiotics.
Years of research have demonstrated how important the gut microbiome is to many aspects of our health. For example, studies have shown that the microbiome influences everything from breast cancer and multiple sclerosis to blood sugar levels and personality.
For the microbiome to be effective, it requires a symbiotic relationship between the beneficial and not-so-beneficial bacteria that colonize specific areas of the gut. A new study led by the Carnegie Institution for Science (Carnegie Science) has discovered a way of guiding bacteria to the region where they'll be of most benefit.
"We're talking about an incredibly complex system of interconnected microbial communities, and each species needs to get to the right place where it can thrive and contribute to host health," said William Ludington from Carnegie Science's Department of Ecology and Evolutionary Biology and the study's corresponding author. "Researchers have been trying to figure out how each bacterial species is directed to the right location and how colonization by harmful or less-than-ideal species is minimized."
The researchers liken the process to an airport's baggage handling system, where checked luggage - in this case, beneficial bacteria - is conveyed from the check-in counter to a plane's cargo hold. Outwardly, it appears chaotic, but most of the time, the luggage is delivered to the right plane. If it isn't, there are corrective processes in place.
"Likewise, in the gut, beneficial bacteria need to get to the region where they can successfully create a colony," said Karina Gutiérrez-García, the study's co-lead author. "We worked to reveal the mechanisms that enable this to happen."
To figure out how symbiotic microbiome species got to where they needed to go, their so-called niche, the researchers developed technology that enabled them to watch a single cell of the beneficial bacterial species Lactiplantibacillus plantarum colonize the gut of a fruit fly in high-res and in real-time. The fruit fly was chosen because its microbiome is much smaller than that of humans and is well-defined.
"Developing this imaging technique was an exciting challenge," said study co-author Ren Dodge. "It allowed us to see the interactions of individual bacteria cells with the host gut in unprecedented detail."
Successful colonization relies on proteins called adhesins, which are present on the surface of bacteria. As their name suggests, adhesins stick to other cells, tissues or structures in the body. However, adhesins are usually non-discriminant about where they adhere and the attachment transient.
Using their live imaging tech, the researchers observed that adhesins used by L. plantarum isolated from wild fruit flies stably attached to host gut tissue. In contrast, human-sourced L. plantarum only formed a short-lived attachment. Looking more closely, they identified the genetic basis for the bacteria's improved adhesion within a specific gut niche.
"By identifying the genes that enable L. plantarum to colonize specific niches, we now have the insights into how to engineer greater precision into other bacteria," said co-lead author Kevin Aumiller. "This opens the door to creating probiotics that are optimized for specific niches in the human gut."