Real-Time Imaging Reveals the Dynamics of Microbial Colonization in the Gut

A research team led by Carnegie Science's Will Ludington, Karina Gutiérrez-García, and Kevin Aumiller has identified genes that allow a beneficial bacterial species to colonize specific areas of the gastrointestinal tract. Published last week in Science, their findings could transform the understanding of gut microbiome composition and pave the way for advances in microbiome engineering.

The gut microbiome comprises hundreds to thousands of microbial species residing in the human body, significantly impacting health, fertility, and longevity. These microbial populations support digestion, modulate immune responses, and combat pathogens, among other critical functions.

However, the microbiome varies across the gut. Just as different organs in the gastrointestinal system specialize in food digestion and nutrient absorption, distinct microbial communities inhabit specific zones, performing unique roles in each region.

Multiple factors depend on the successful colonization of various regions within the gastrointestinal tract by different microbial populations. These include the bacteria's nutrient needs, local pH levels, dissolved oxygen content, competition with other bacterial strains, and the ability to survive harsh conditions such as stomach acid, bile salts, and immune-response cells.

“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,” details Ludington, who has been probing microbiome acquisition and composition for several years at Carnegie.

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.”

Will Ludington, Carnegie Science

Imagine checked luggage navigating a network of conveyor belts behind the scenes at a bustling urban airport. While the baggage handling system might appear disorganized and chaotic, most bags reach their intended planes successfully. Mechanisms are in place to address and correct any sorting errors that arise during the process.

Likewise, in the gut, beneficial bacteria need to get to the region where they can successfully create a colony. We worked to reveal the mechanisms that enable this to happen.”

Karina Gutiérrez-García, Study Co-Lead Author, Carnegie Science

Successful colonization relies on proteins in bacterial cell walls known as adhesins. These proteins adhere to various surfaces within the body, often binding non-specifically, which means they can attach to multiple tissue types.

This raises the question: how do symbiotic microbiome species navigate to their specific destinations?

To address this question, Ludington, Gutiérrez-García, Aumiller, and their team developed a technology that allowed them to observe a single cell of the bacterial species Lactiplantibacillus plantarum colonizing its niche in the fruit fly gut in real-time.

The research team also included Carnegie’s Ren Dodge, Benjamin Obadia, Haolong Zhu, and Ru-Ching Hsia, along with Ann Deng, Sneha Agrawal, and Xincheng Yuan from Johns Hopkins University, and Richard Wolff and Nandita Garud from UCLA.

Although the fruit fly is often seen as a kitchen pest, it is a valuable model organism in the laboratory. Its microbiome is well-defined and consists of a limited number of species, making it ideal for this type of research.

Observing the events in such high-resolution detail allowed the scientists to distinguish between short-lived colonization and sustained long-term success.

“Developing this imaging technique was an exciting challenge,” said Dodge, a key contributor to the research. “It allowed us to see the interactions of individual bacteria cells with the host gut in unprecedented detail.”

The researchers discovered that L. plantarum isolated from the guts of wild fruit flies could stably attach to host tissue, whereas L. plantarum from humans and other sources only formed temporary attachments.

Using this insight, they sought to uncover the genetic basis for this strong affinity. Through meticulous effort, they identified a specific set of genes responsible for symbiotic gut colonization within a 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. This opens the door to creating probiotics that are optimized for specific niches in the human gut.”

Kevin Aumiller, Study Co-Lead Author, Carnegie Science

“Looking ahead, we will attempt to elucidate the mechanism underlying this binding specificity,” Ludington concluded.