New research suggests gut bacteria may play a more active role in digestion than previously understood by recycling hormones that help keep the colon moving. A study published in Nature Neuroscience found that certain gut microbes help reactivate testosterone, which then signals neurons in the gut to maintain normal intestinal transit.
Researchers discovered that androgen signaling, specifically testosterone, to neurons in the enteric nervous system is required for normal intestinal movement in mice. This signaling depends on the microbiome to function. The enteric nervous system, a network of neurons embedded in the gut wall, contains specific neurons called NOS1+ enteric neurons that produce nitric oxide and help regulate movement 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 significantly. Serum testosterone levels fell, and intestinal transit slowed. Restoring androgen signaling was partly enough to fix the movement problems, suggesting the hormone pathway is a key driver of the effect, not just bacterial diversity.
The study explains how gut bacteria recycle hormones. After the body uses testosterone, the liver deactivates it by attaching a glucuronide molecule and excretes it into the gut. Certain gut bacteria produce enzymes that 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 signals the neurons that keep digestion moving. The researchers confirmed this mechanism directly, showing the bacteria were performing a specific biochemical function that gut neurons depend on.
The study also found that NOS1+ enteric neurons increase androgen receptor expression after puberty, matching shifts in fecal bacterial enzyme activity. This timing suggests the microbiome and hormonal system develop together in a coordinated way.
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 movement at all. When androgen signaling was already absent, antibiotics had less additional impact on motility. This suggests antibiotic-induced disruption of digestion is at least partly caused by this hormone pathway, not just a general reduction in microbial diversity.
This research adds to evidence that the microbiome actively participates in hormone metabolism. Gut bacteria have been found to synthesize or break down androgens in conditions like prostate cancer and depression. This study shows microbial hormone reactivation also plays a role in healthy, everyday gut function. While the study was conducted in mice, researchers found that human colonic enteric neurons express androgen receptors in both males and females, and human gut bacteria produce the same enzymes that metabolize androgen glucuronides.
The findings offer context for understanding why gut disruption after antibiotics can feel more significant than a simple reduction in probiotic bacteria. Antibiotics affect more than diversity; they may interfere with specific microbial functions like hormone reactivation that influence gut motility through distinct pathways. Supporting a thriving microbiome with a diet rich in fiber and fermented foods helps maintain 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 takeaway is that the microbiome may be actively maintaining the hormonal environment that gut neurons need to function, a level of sophistication that science is only beginning to map.
