A key question remains. Which chemical signals matter most to beneficial gut bacteria?

Moving Beyond Pathogens in Microbiology Research

Until now, much of what scientists understand about bacterial sensing has come from studying model organisms, especially disease-causing bacteria. Far less attention has been given to commensals, the non-pathogenic or beneficial microbes that naturally live in the human body. This gap has left researchers wondering what kinds of chemical information these helpful bacteria are actually detecting in their environment.

An international research team led by Victor Sourjik set out to address that question. The group included scientists from the Max Planck Institute for Terrestrial Microbiology, the University of Ohio and the Philipps-University Marburg. Their work focused on Clostridia, a group of motile bacteria found in large numbers in the human gut that are known to support gut health.

Gut Bacteria Detect a Wide Range of Nutrients

The researchers found that receptors from the human gut microbiome can recognize a surprisingly broad array of metabolic compounds. These substances include breakdown products from carbohydrates, fats, proteins, DNA, and amines. Through systematic screening, the team also identified clear patterns. Different types of bacterial sensors showed distinct preferences for certain classes of chemicals.

This finding revealed that gut bacteria are not responding randomly to their environment but are selectively tuned to specific metabolic signals.

Lactate and Formate Stand Out as Key Signals

By combining laboratory experiments with bioinformatic analysis, the researchers identified multiple chemical ligands that bind to sensory receptors controlling bacterial movement. These receptors help motile bacteria detect nutrients that are especially valuable for growth. The results suggest that movement in these bacteria is primarily driven by the search for food.

Among all the chemicals tested, lactic acid (lactate) and formic acid (formate) appeared most frequently as stimuli. This suggests that these compounds may serve as especially important nutrient sources for gut bacteria.

Cross-Feeding Supports a Healthy Microbiome

Some gut bacteria can produce lactate and formate themselves, highlighting the importance of ‘cross-feeding’. In this process, one bacterial species releases metabolites that other species use as food. This kind of cooperation helps stabilize the gut ecosystem.

“These domains appear to be important for interactions between bacteria in the gut and could play a key role in the healthy human microbiome,” explains Wenhao Xu, a postdoctoral researcher in Victor Sourjik’s research group and the study’s first author.

Discovery of New Sensory Receptors

Through a systematic analysis of multiple sensors, the team identified several previously unknown groups of sensory domains. These newly characterized sensors are specific for lactate, dicarboxylic acids, uracil (a RNA building block) and short-chain fatty acids (SCFAs).

The researchers also determined the crystal structure of a newly discovered dual sensor that responds to both uracil and acetate. This allowed them to understand how these molecules bind to the sensor at a molecular level. The sensor belongs to a large family of sensory domains with diverse functions.

Evolution Shows Remarkable Flexibility

By examining evolutionary relationships between uracil sensors and related sensory domains, the team found that ligand specificity can change relatively easily over time. This flexibility helps explain how bacteria adapt their sensing abilities as their environments change.

“Our research project has significantly expanded the understanding of sensory abilities of beneficial gut bacteria,” says Victor Sourjik. “To our knowledge, this is the first systematic analysis of the sensory preferences of non-model bacteria that colonise a specific ecological niche. Looking ahead, our approach can be similarly applied to systematically investigate sensory preferences in other microbial ecosystems.”