Magnesium Orotate and the Microbiome–Gut–Brain Axis Modulation: New Approaches in Psychological Comorbidities of Gastrointestinal Functional Disorders Original paper

What was reviewed?

This narrative review examined how magnesium, and especially magnesium orotate, may modulate the microbiome–gut–brain axis in functional gastrointestinal disorders that commonly overlap with anxiety and depression. The authors pulled together recent animal and human evidence on magnesium’s effects on gut physiology, inflammation, neurotransmission, and microbial metabolism, then focused on whether magnesium orotate could act as an adjuvant alongside probiotics and standard therapies. The review also compared the plausibility of these approaches in adults versus children, with an emphasis on dysbiosis-driven symptom loops.

Who was reviewed?

The review covered evidence from both animal models and human studies, prioritizing recent literature and open-access full-text reports. The “who” therefore included experimental rodents exposed to magnesium deficiency or magnesium supplementation and then assessed for microbiome shifts and behavior-like outcomes, plus human cohorts with gut–brain axis conditions. These human populations included adults with major depression who showed suboptimal response to SSRIs and then received adjunct magnesium orotate, and patients with functional gastrointestinal disorders where psychological comorbidities commonly accompany GI symptoms. The pediatric perspective drew on children and adolescents with functional GI symptoms and neurodevelopmental conditions linked to dysbiosis.

What were the most important findings?

Across the reviewed evidence, magnesium intake repeatedly acted as a microbiome-sensitive signal that can change short-chain fatty acid output, immune tone, and stress-related behaviors. The review highlighted that magnesium shifts can alter microbial diversity and specific taxa in time- and dose-dependent ways, with animal data showing links between magnesium deficiency, increased inflammatory cytokine signaling, reduced overall diversity over time, and anxiety- or depression-like behavior. For microbiome signatures, the review emphasized psychobiotic candidates such as Lactobacillus and Bifidobacterium as gut–brain relevant genera and noted that magnesium status may influence these groups and related metabolite pathways. Importantly, small pilot human studies suggested that adding magnesium orotate to SSRI regimens, and especially combining magnesium orotate with probiotics, coincided with improved depression and anxiety scores, with relapse reported when patients returned to SSRI-only therapy.

What are the greatest implications of this review?

For clinicians, the review supports treating magnesium status as a practical, modifiable lever within gut–brain axis care, while also warning that responses may vary by baseline magnesium state, gut inflammation, and microbiome context. The biggest clinical implication is that magnesium orotate may offer a dual-action strategy: it can improve magnesium bioavailability and potentially support microbial and neurochemical pathways tied to symptom severity in functional GI disorders with psychological comorbidity. For a microbiome signatures database, the review frames magnesium as a factor that can reshape “psychobiotic” patterns and inflammatory signaling, making magnesium intake a key metadata variable when interpreting associations between taxa, mood symptoms, and functional GI outcomes.