A new study published in Cell from the lab of MCB faculty member Nick Bellono reveals that octopuses detect microbial cues on surfaces to distinguish prey and eggs from inanimate objects—an astonishing example of how animals can sense their environment through the invisible world of microbiomes.
The research, led by postdoctoral fellow Rebecka Sepela, uncovers a new paradigm: that animal behavior can be directly guided by microbial communities in the environment. By combining sensory biology, microbiology, molecular evolution, and structural biology, the study shows how octopuses integrate chemical signals produced by environmental microbes into their decision-making, informing behaviors as distinct as hunting and caring for offspring.
“What Rebecka found is how microbes inform the octopus of which potential prey surfaces are worth pursuing and which egg surfaces are worth nurturing,” Bellono explains.
A New Role for Microbes in Animal Sensing
Octopuses are famously curious, exploring the seafloor with their arms to identify food and shelter. Previous work from the Bellono lab characterized a family of sensory receptors found in the octopus’s arms that allow them to “taste by touch.” These receptors are particularly tuned to detect poorly soluble molecules—chemicals that don’t travel far in water and tend to stay near surfaces.
“We started with the question: What do octopuses actually sense from their environment?” Bellono says. “These receptors seemed ideal for picking up cues from the surfaces they probe.”
What Sepela discovered was surprising: the key wasn’t the surface itself, but the microbiome growing on that surface. In other words, octopuses aren’t just sensing prey or eggs directly—they’re detecting the microbes that grow on them.
“We asked how microbial information was being relayed to the octopus sensory system,” says Sepela. “These receptors lie at the interface between the external environment and the nervous system, so we wondered what kinds of microbes could activate them.”
Screening Hundreds of Microbes for Molecular Signals
To tackle that question, Sepela designed an ambitious screen. She cultured nearly 300 strains of microbes collected from the octopus’s natural habitat and tested whether they could activate the octopus’s sensory receptors.
“The idea was, if a microbial strain could activate a receptor, then it could generate a neural signal that tells the octopus: This is something I care about,” Sepela explains.
The results were clear. A few specific microbes activated the receptors, and those microbes were especially enriched in microbiomes found on decaying prey or unhealthy eggs—the kinds of surfaces an octopus needs to distinguish quickly.
“We then asked: What are these microbes producing that allows them to communicate with the octopus?” says Sepela. “Microbes are chemical factories. They constantly take in environmental cues and produce molecules that reflect their surroundings.”
Using a collaborative, interdisciplinary approach, Sepela and her colleagues isolated the exact molecules that triggered the octopus receptors. That effort involved partnerships with researchers in Jon Clardy’s lab at Harvard Medical School, which specializes in natural product discovery. Then with structural biologists in Ryan Hibbs’ lab at the University of California, San Diego, they revealed how those molecules bound and activated the octopus receptors.
Behavior Guided by Microbial Chemistry
Once they identified the molecules, the team could link receptor activation to octopus behaviors in the wild. For example, a particular microbe found on decaying crabs produced a chemical that told the octopus the prey was no longer fresh. Another microbe found on rejected eggs released a compound associated with eggs that mothers had rejected from their clutches.
“The microbiome is acting almost like a chemical translator,” Sepela says. “It integrates environmental signals—like changes in temperature or nutrient levels—and outputs molecules that inform the octopus how to behave.”
This microbial “language” is constantly shifting in response to environmental conditions, and the octopus is attuned to these shifts. A surface covered with healthy microbial communities might trigger nurturing behavior; another, with microbial signatures of decay, might be avoided—or indicate a meal.
“In a comparative way, we found microbial strains that distinguish between live and decaying prey, and between viable and non-viable eggs,” Sepela says. “And those microbes produce molecules that allow the octopus to tell the difference.”
A Model for Microbe-Driven Behavior Across Species
Although the work focuses on octopuses, Bellono and Sepela believe the implications extend far beyond a single species.
“This might seem like a very specific case—an octopus exploring the seafloor,” Bellono says. “But what we’re seeing is actually a general rule about how organisms sense microbiomes.”
In humans, for instance, the microbiome has been linked to a wide range of conditions, including digestion and anxiety. However, the complexity of these internal microbial ecosystems
makes it challenging to attribute specific molecules to specific effects. The octopus model, by contrast, offers a simplified system: one receptor, one microbial strain, one behavioral output.
“The octopus gives us a way to study cross-kingdom communication with reduced complexity,” Bellono says. “It’s a system where we can link a microbial signal directly to a behavior—whether that’s predation or parental care.”
This idea has even deeper evolutionary roots. Sepela notes that the closest known animal relatives, choanoflagellates, transition from single-cell to multicellular life in response to microbial cues—suggesting that microbial signaling may have shaped animal evolution from the very beginning.
In addition to its scientific insights, Bellono and Sepela see this work as a testament to the value of basic, curiosity-driven research.
“This project grew out of a simple question: How does the octopus use its arms?” Bellono recalls. “By following that question, we ended up uncovering a new way that animals sense their world. Across life, evolution, and organ systems, microbes are essential—and this study shows another example of how deeply they influence physiology and behavior.”
