{
  "abstract": "The human gut harbors a complex and diverse microbial ecosystem—collectively termed the gut microbiota—that exerts profound effects on host physiology, including brain function. This bidirectional communication, known as the gut–brain axis, integrates neural, immunological, and neuroendocrine pathways, enabling gut microbiota to modulate neurotransmitter synthesis and signaling. Disruption of this microbial balance, or dysbiosis, has been increasingly implicated in the pathogenesis of major neuropsychiatric disorders. 1This review synthesizes current evidence linking gut microbiota to the regulation of four key neurotransmitter systems—tryptophan/serotonin, dopamine, gamma-aminobutyric acid (GABA), and glutamate—and their roles in four prevalent psychiatric conditions: schizophrenia, depression, generalized anxiety disorder (GAD), and autism spectrum disorder (ASD).2Emerging studies reveal that gut microbiota influence tryptophan metabolism and peripheral serotonin production via bacterial metabolites and immune modulation, thereby impacting mood and stress regulation.3 Similarly, certain taxa enhance dopamine synthesis or protect dopaminergic neurons, while others promote neuroinflammation and dopamine depletion.4 GABA production by Lactobacillus, Bifidobacterium, and other genera affects inhibitory signaling in the brain, with implications for anxiety, depression, and neurodegeneration. Furthermore, alterations in gut composition can shift glutamate–GABA balance, influencing synaptic plasticity and cognitive functions.2 5 6Clinical and preclinical data consistently demonstrate altered microbial signatures in neuropsychiatric disorders. In schizophrenia, dysbiosis correlates with neuroinflammatory pathways, neurotransmitter imbalances, and treatment-resistant psychosis.7 Depression is associated with reduced microbial diversity and shifts in serotonin- and dopamine-producing bacteria, contributing to HPA axis dysregulation.2 In GAD, decreased abundance of short-chain fatty acid–producing genera and impaired serotonin availability exacerbate anxiety symptoms.2 8 ASD presents with distinctive microbial patterns and comorbid gastrointestinal dysfunction, with evidence that microbiome-targeted interventions can improve behavioral and GI outcomes.9Therapeutic strategies targeting gut microbiota—such as probiotics, prebiotics, dietary modification, and fecal microbiota transplantation (FMT)—show promise in modulating neurotransmitter pathways and alleviating psychiatric symptoms. Notably, interventions like microbiota transfer therapy in ASD have demonstrated sustained improvements in both gastrointestinal and behavioral domains. However, mechanistic understanding remains incomplete, and inter-individual variability in microbiome composition poses a challenge for standardized therapies.2 10The gut–brain axis offers a compelling framework for understanding the interplay between microbial ecology and mental health. By elucidating the molecular mechanisms underlying microbiota–neurotransmitter–behavior relationships, this field may pave the way for novel, microbiome-based interventions that complement existing psychiatric treatments. Future research should focus on longitudinal, multi-omics approaches, personalized microbiota modulation, and integration of microbiome profiles into precision psychiatry.2 11Reference Generoso JS, Giridharan VV, Lee J, et al. The role of the microbiota- gut-brain axis in neuropsychiatric disorders. Braz J Psychiatry. 2021;43:293–305.Amjad Mhanna, Nafiza Martini, Ghefar Hmaydoosh, George Hamwi, Mulham Jarjanazi, Ghaith Zaifah, Reem Kazzazo, Aya Haji Mohamad, Zuheir Alshehabi. The correlation between gut microbiota and both neurotransmitters and mental disorders: a narrative review. Medicine February 02 2024;103(5):e37114. | DOI: 10.1097/MD.0000000000037114 Thangaleela S, Sivamaruthi BS, Kesika P, et al. Role of probiotics and diet in the management of neurological diseases and mood states: a review. Microorganisms. 2022;10:2268.Hamamah S, Aghazarian A, Nazaryan A, et al. Role of microbiota- gut-brain axis in regulating dopaminergic signaling. Biomedicines. 2022;10:436.Dicks LMT. Gut bacteria and neurotransmitters. Microorganisms. 2022;10:1969.Tian XY, Xing JW, Zheng QQ, et al. 919 syrup alleviates postpartum depression by modulating the structure and metabolism of gut microbes and affecting the function of the hippocampal GABA/Glutamate system. Front Cell Infect Microbiol. 2021;11:694443.Seeman MV. The gut microbiome and treatment-resistance in schizophrenia. Psychiatr Q. 2020;91:127–36.Stopińska K, Radziwoń-Zaleska M, Domitrz I. The microbiota- gut-brain axis as a key to neuropsychiatric disorders: a mini review. J Clin Med. 2021;10:4640.Ristori MV, Quagliariello A, Reddel S, et al. Autism, gastrointestinal symptoms and modulation of gut microbiota by nutritional interventions. Nutrients. 2019;11:2812–21.Kang DW, Adams JB, Gregory AC, et al. Microbiota transfer therapy alters gut ecosystem and improves gastrointestinal and autism symptoms: an open-label study. Microbiome. 2017;5:1–16.Srikantha P, Hasan Mohajeri M. The possible role of the microbiota-gut-brain-axis in autism spectrum disorder. Int J Mol Sci. 2019;20:14–9.",
  "authors": [
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic",
        "Stemosis for Scientific Research, Damascus, SYR"
      ],
      "name": "Amjad Mhanna"
    },
    {
      "affiliations": [
        "Stemosis for Scientific Research, Damascus, SYR",
        "Damascus University, Faculty of Medicine, Damascus, SYR",
        "University of Illinois at Chicago, Department of Medicine, Chicago, Il, USA"
      ],
      "name": "Nafiza Martini"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic",
        "Stemosis for Scientific Research, Damascus, SYR"
      ],
      "name": "Ghefar Hmaydoosh"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic",
        "Stemosis for Scientific Research, Damascus, SYR"
      ],
      "name": "George Hamwi"
    },
    {
      "affiliations": [
        "Aleppo Universiy, Faculty of Medicine, Aleppo, SYR"
      ],
      "name": "Mulham Jarjanazi"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic",
        "Stemosis for Scientific Research, Damascus, SYR"
      ],
      "name": "Ghaith Zaifah"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic",
        "Stemosis for Scientific Research, Damascus, SYR"
      ],
      "name": "Reem Kazzazo"
    },
    {
      "affiliations": [
        "Stemosis for Scientific Research, Damascus, SYR",
        "Aleppo Universiy, Faculty of Medicine, Aleppo, SYR"
      ],
      "name": "Aya Haji Mohamad"
    },
    {
      "affiliations": [
        "Stemosis for Scientific Research, Damascus, SYR",
        "Department of Pharmacology, Tartous University, Tartous, SYR"
      ],
      "name": "Samer Younes"
    },
    {
      "affiliations": [
        "Faculty of Medicine, Tishreen University, Latakia, Syrian Arab Republic"
      ],
      "name": "Zuheir Alshehabi"
    }
  ],
  "title": "OC96 Microbiota–neurotransmitter crosstalk: unlocking the gut–brain axis for novel psychiatric therapies",
  "uid": "4123d438-4bdb-5742-8a2e-41461eebc614"
}