Alleviating depression in mice by restoring gut microbiome

Depression is a significant challenge to diagnose and treat. Among the factors influencing depression onset and severity, there is growing evidence for chemical imbalances that generate oxidative stress throughout the body. To address this problem, researchers reporting in the ACS journal Langmuir developed antioxidant carbon dot nanozymes (synthetic enzyme-like substances) that reduced oxidative stress, rebalanced gut microbes and alleviated stress-induced depression in rats.

Mental health disorders such as depression not only reduce quality of life for affected individuals but also challenge public health and economic prosperity. One of the potential hallmarks of depressive disorder is a buildup of reactive oxygen- and nitrogen-containing compounds, which can overwhelm the body’s natural defenses. And the resulting oxidative stress impacts gut health by disrupting the balance of microbes, which can trigger inflammation and alter brain and neuronal function. To correct this problem, Jihong Huang, Weiwei He and colleagues synthesized enzyme-like substances with strong antioxidant capacity to reduce the reactive species and thereby restore gut microbe balance and alleviate depression.

The researchers created carbon dot nanozymes (CDzymes) by polymerizing glucose and the amino acid histidine to ensure antioxidant activity while maintaining biocompatibility. The CDzymes neutralized a range of reactive species in solution and in cultured mouse nerve cells without signs of toxicity. The researchers then moved to a rat model of depression known as chronic and unpredictable mild stress (CUMS). They compared animals in four groups — healthy rats, untreated CUMS rats, and CUMS rats treated with either gamma-aminobutyric acid (GABA), an antidepressant drug that inhibits nerve signaling, or CDzymes. Rats receiving either treatment displayed less depressive behavior than untreated CUMS rats in terms of reward-seeking, curiosity, willingness to explore and resistance to despair. The behavioral improvements observed with GABA or CDzymes treatment also aligned with improved levels of several depression-related neurotransmitters isolated from brain tissues.

The researchers then explored the impact of CUMS and treatment on the rodents’ gut microbiome by analyzing fecal microbes. Although microbial richness and diversity was greatly reduced in the depressed animals, this reduction was largely reversed to the same degree with GABA or CDzymes treatment. Additionally, the types of microbes present in the feces of treated rats was much closer to that of healthy rats, highlighting the link between gut health and mental health. This microbial restoration also resulted in improved metabolism of several amino acids critical to nerve signalling. Taken together, these results present CDzymes as effective as GABA in animal studies, making it another potential therapeutic option for addressing depressive disorder.

The authors acknowledge funding from the Central Government Guides the Local Science and Technology Development Special Fund, the Key Research and Development Project of Henan Province, and the Collaborative Innovation Center of Functional Food by Green Manufacturing.

###

The American Chemical Society (ACS) is a nonprofit organization chartered by the U.S. Congress. ACS’ mission is to advance the broader chemistry enterprise and its practitioners for the benefit of Earth and all its people. The Society is a global leader in promoting excellence in science education and providing access to chemistry-related information and research through its multiple research solutions, peer-reviewed journals, scientific conferences, e-books and weekly news periodical Chemical & Engineering News. ACS journals are among the most cited, most trusted and most read within the scientific literature; however, ACS itself does not conduct chemical research. As a leader in scientific information solutions, its CAS division partners with global innovators to accelerate breakthroughs by curating, connecting and analyzing the world’s scientific knowledge. ACS’ main offices are in Washington, D.C., and Columbus, Ohio.

Registered journalists can subscribe to the ACS journalist news portal on EurekAlert! to access embargoed and public science press releases. For media inquiries, contact newsroom@acs.org.

Note: ACS does not conduct research but publishes and publicizes peer-reviewed scientific studies.

Follow us: X, formerly Twitter | Facebook | LinkedIn | Instagram