New research suggests gut bacteria play an active role in recycling hormones that help keep digestion moving, and that antibiotics may disrupt this process in a specific way.
A study published in Nature Neuroscience found that androgen signaling, specifically testosterone, to neurons in the enteric nervous system is required for normal intestinal transit in mice. This signaling depends on the microbiome to function.
The enteric nervous system is a network of neurons in the gut wall. Within it, a group of neurons called NOS1+ enteric neurons produce nitric oxide and appear to regulate propulsive motor activity in the colon. A separate group of spinal afferent neurons also express androgen receptors and contribute to motility.
When researchers depleted the gut microbiome in mice using broad-spectrum antibiotics, androgen receptor expression in enteric neurons dropped, serum testosterone levels fell, and intestinal transit slowed. Restoring androgen signaling was partly enough to fix the motility deficits, suggesting the hormone pathway is a meaningful driver of the effect.
The study explains how this works. Testosterone does not disappear after the body uses it. The liver deactivates it by attaching a glucuronide molecule and excretes it into the gut. Under normal conditions, certain gut bacteria produce enzymes that help reactivate the testosterone so it can bind to androgen receptors in gut neurons.
This creates a recycling loop. The body excretes a deactivated hormone, gut bacteria reactivate it, and it goes back to work signaling the neurons that keep digestion moving. The researchers confirmed this mechanism directly.
Why antibiotics disrupt digestion
Broad-spectrum antibiotics can eliminate the specific bacterial populations responsible for producing these enzymes. Without those enzymes, the testosterone recycling loop breaks down. Androgen receptor expression in enteric neurons falls, serum testosterone drops, and the colon slows.
The researchers found that androgens were necessary for antibiotics to affect transit at all. When androgen signaling was already absent, antibiotics had less additional impact on motility. This suggests the antibiotic-induced disruption of digestion is at least partly mediated through this hormone pathway.
The study adds to evidence that the microbiome is an active participant in hormone metabolism. Gut bacteria have been identified that can synthesize or break down androgens in conditions like prostate cancer and depression. This study adds evidence that microbial hormone reactivation plays a role in healthy, everyday gut function.
While the study was conducted in mice, the researchers found that human colonic enteric neurons express androgen receptors in both males and females. Human gut bacteria also produce the same enzymes capable of metabolizing androgen glucuronides.
What this means for gut health
This research offers context for understanding why gut disruption after antibiotics can feel significant. The disruption may include interference with specific microbial functions like hormone reactivation that influence gut motility through distinct pathways.
A thriving microbiome depends on a diet rich in fiber and fermented foods, which supports the bacterial populations that produce these enzymes. After a course of antibiotics, the microbiome can take weeks to months to return to baseline.
The broader finding is that the microbiome may be actively maintaining the hormonal environment that gut neurons need to function. This is a level of sophistication that science is only beginning to map.
