The aggressive use of antibiotics could fuel mood disorders and anxiety
Antibiotics (ABs) are among the most used pharmaceutical drugs worldwide, as they are currently the most effective medicines for the treatment of bacterial infections. An excessive use of these drugs, however, can damage the gut microbiota, the population of microorganisms living in the intestines that help us to digest food.
Bacteria and other microorganisms in the gut are known to also communicate with the brain via a communication pathway that is referred to as the gut-brain axis. Recent research suggests that some gut bacteria help to reduce inflammation and support the healthy functioning of the brain.
Researchers at the First Affiliated Hospital of Chongqing Medical University have carried out a study exploring the possibility that the effects of ABs on gut bacteria could also facilitate the development of mental health disorders, particularly increasing anxiety. Their findings, published in Molecular Psychiatry, suggest that ABs do in fact damage gut bacteria that help regulate mood, linking their excessive use with higher levels of anxiety.
“ABs are widely abused in medicine and may be a risk factor for mental health,” wrote Ke Xu, Yi Ren and their colleagues in their paper. “To better understand their effects, we observed mental disorder symptoms in AB-treated mice and patients and investigated possible mechanisms.”
The effects of antibiotics on the gut and brain
As part of their study, Xu, Ren and their colleagues carried out a series of experiments involving adult mice and humans. In the first set of experiments, they administered ABs to mice, then observed their behavior and analyzed microbiomes in their feces, comparing both to those of mice who did not receive Abs.
“Using AB-treated mice, we found obvious anxiety-like behaviors, along with differential gut microbiota (mainly Firmicutes and Bacteroidota), reduced short-chain fatty acids (SCFAs), and disrupted gut-brain lipid metabolism,” wrote Xu, Ren and their colleagues. “Acetylcholine decreased in feces, colon wall, serum, and hippocampus of AB-treated mice, and this reduction was significantly correlated with anxiety-like behaviors.”
The researchers subsequently performed an additional experiment, where they collected stool and blood samples from three groups of people, while also asking them how anxious they felt. The first had recently taken antibiotics, did not take antibiotics and others who were healthy and did not require any AB treatment.
“Using AB-treated patients (n = 55), AB-naïve patients (n = 60), and healthy controls (n = 60), we also observed the obvious anxiety symptoms in AB-treated patients, along with differential gut microbiota (mainly Firmicutes), reduced SCFAs, and disrupted lipid metabolism in feces and serum,” wrote the authors. “AB-treated patients showed consistently lower serum and fecal acetylcholine, which was highly correlated with anxiety symptoms.”
Reversing the effects of ABs on mental health
When they analyzed the data they collected, the researchers found that the use of ABs was linked to anxiety-like behaviors in mice and higher levels of anxiety in humans. Moreover, the drugs appeared to reduce the amounts of some helpful gut bacteria, particularly those in the Bacteroides group.
In addition, the team found an association between the intake of ABs and a reduction in the neurotransmitter acetylcholine, a chemical that supports communication between nerve cells. Mice and human patients who had received ABs were found to have lower levels of acetylcholine both in the gut and brain compared to those who had not taken ABs.
“In both AB-treated mice and patients, co-occurrence analysis indicated that the Bacteroides-acetylcholine pair may play an important role in AB-induced anxiety,” wrote Xu, Ren and their colleagues.
“At the species level, Bacteroides_caecimuris in AB-treated mice and Bacteroides_plebeius in AB-treated patients were both decreased and significantly correlated with acetylcholine. Furthermore, exogenous methacholine (an acetylcholine derivative) intervention effectively alleviated anxiety-like behaviors and suppressed hippocampal microglial activation in AB-treated mice.”
Overall, the results of this study suggest that the excessive use of ABs could not only alter the gut microbiota, but it could also increase levels of anxiety and adversely impact people’s mental health. In the future, this work could inspire further research exploring the impact of AB intake on mental health, potentially also informing the development of therapeutic strategies aimed at re-balancing the gut microbiome after treatment with ABs.
“Our findings highlight the harmful effects of aggressive AB treatment on mood and show the potential of acetylcholine or its derivative to reverse this effect,” added the authors.
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