Deep inside the colon, an unseen partnership between bacteria and nerve cells is quietly orchestrating the movement of food, fluids and waste through the intestines—a discovery that researchers at Boston Children's Hospital have only recently begun to understand.
Millions of people worldwide struggle with gut-related conditions like irritable bowel syndrome, gastroesophageal reflux disease and gastroenteritis. For decades, scientists have known that intestinal movement—the coordinated contractions that push material through the digestive tract—involves a symphony of systems: muscles, hormones, neurons and nerves. But a crucial player has been hiding in plain sight: the gut microbiome itself. A team led by Meenakshi Rao at Boston Children's Hospital, working with colleagues from Harvard Medical School, the University of North Carolina at Chapel Hill and Laval University, has now identified a previously unknown mechanism by which gut bacteria influence how the colon functions, published in Nature Neuroscience.
The insight came through a series of elegant experiments. The researchers gave mice antibiotics to wipe out their gut bacteria, then measured what happened to specific hormones called androgens and to intestinal motility. When the microbiome vanished, so did the healthy hormone signaling that keeps the gut moving properly. But then they discovered something remarkable: bacteria weren't simply producing hormones themselves. Instead, they were activating hormones that the body had already made but left inactive. The team identified a bacterial enzyme called glucuronidase—or GUS—that metabolizes inactive androgen-glucuronides into their active forms, essentially unlocking hormonal signals that nerve cells depend on.
To prove this, Rao's team delivered the engineered microbial enzyme directly into the colons of antibiotic-treated mice. The results were striking: the enzyme alone was enough to restore androgen signaling in the specific nerve cells that control gut movement, even without the full microbial community present. Using immunohistochemistry to visualize neurons and genetic engineering to understand which cell types mattered most, the researchers mapped a precise biological pathway: gut bacteria produce an enzyme that activates sex hormones, which then signal to specific nerve cells called NOS1+ enteric neurons, which in turn regulate how the intestines contract and move.
"The colon is an organ in which a lot of different systems in the body converge, including hormones, bacteria, immune cells and nerves," Rao explained. This study reveals how intricately these systems are woven together. The discovery also hints at something larger: if a single bacterial enzyme can restore this signaling, then targeted interventions might one day help people with motility disorders or other gut conditions that affect millions.
The research points toward a future where treating digestive problems might mean restoring not just the bacteria themselves, but understanding the specific molecular conversations happening between microbes and the human body. For now, the findings offer a window into the profound complexity of gut health—and a reminder that sometimes the most important biological partnerships are the ones we can't even see.