Gut-brain connection in schizophrenia: A narrative review

Table 1 Overview of the roles and implications of various gut hormones and neuropeptides in appetite regulation, energy balance, and mood

Hormone/ neuropeptide	Source	Function	Mechanism of action	Clinical implications
Ghrelin	Stomach	Stimulates appetite	Activates neurons in the hypothalamus; levels increase before meals and decrease afterward	Implicated in meal initiation; dysregulation linked to impulsivity and risk-taking behaviors in schizophrenia
Leptin	Adipose tissue	Inhibits hunger	Signals the brain regarding energy stores; reduces appetite	Dysregulation associated with obesity and metabolic disorders
Peptide YY	Small intestine	Promotes satiety and reduces food intake	Secreted postprandially; acts on the hypothalamus	Linked to appetite regulation; imbalances can affect weight management
Glucagon-like peptide 1	Intestines	Promotes satiety; enhances insulin secretion	Acts on receptors in the brain; improves glucose homeostasis	Neuroprotective effects; may counteract Alzheimer’s disease progression by enhancing memory and reducing neuroinflammation
Serotonin	Gut (90% produced)	Regulates motility, secretion, vascular tone, mood, cognition	Alters motility and secretion; regulates mood and emotional states	Alterations linked to depression, anxiety, and irritable bowel syndrome
Neuropeptide Y	Brain	Increases food intake; reduces anxiety-like behavior	Stimulated by stress and fasting; acts on receptors in the brain	Imbalances associated with eating disorders and stress-related behaviors

Table 2 Key gut-derived metabolites, their bacterial sources, their function in the brain, and how they impact mental health and cognition[81,82]

Metabolite	Source (gut bacteria)	Role in the brain	Influence on mental health and cognition
Butyrate	Firmicutes (e.g., Clostridium, Faecalibacterium)	Modulates neuroinflammation, supports neuronal health, regulates neurotransmitter release	Enhances neuroprotection, reduces neuroinflammation, and supports cognitive function; potential to alleviate mood disorders
Gamma-aminobutyric acid	Lactobacillus, Bifidobacterium	Inhibitory neurotransmitter, regulates mood, anxiety, and central GABAergic signaling	Reduces anxiety and stress responses; GABA imbalance linked to mood disorders like depression and anxiety
Homovanillic acid	Bifidobacterium longum	Dopamine metabolite, involved in synaptic integrity and reward pathways	Alleviates depressive symptoms, enhances emotional regulation, and protects synaptic health
Serotonin	Enterococcus, Escherichia, Streptococcus	Regulates mood, cognition, and motor control	Deficiency linked to depression and anxiety; essential for mood regulation and emotional well-being
Acetylcholine	Gut bacteria involved in producing precursors (Lactobacillus, Bifidobacterium)	Key neurotransmitter for motor control, learning, and memory	Deficiency associated with cognitive decline, memory disorders, and Alzheimer’s disease

GABA: Gamma-aminobutyric acid.