From Gut to Brain: The roles of intestinal microbiota, immune system, and hormones in intestinal physiology and gut–brain–axis

📖 Top 20% JournalJun 7, 2025Molecular and cellular endocrinology

How Gut Bacteria, Immunity, and Hormones Affect Gut Function and Communication with the Brain

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Abstract

The gut microbiota significantly influences gut hormones and neurotransmitters in the gut-brain axis.

The gut-brain axis is a communication network between the gastrointestinal tract and the central nervous system, integrating various signals.
Gut microbiota affects the production of hormones such as ghrelin, glucagon-like peptide-1 (GLP-1), and cholecystokinin (CCK), which modulate nutrient absorption and immune responses.
Key gut hormones play roles in appetite regulation, metabolism of nutrients, insulin and glucagon secretion, and influence on mood and cognition.
Dysbiosis, or microbial imbalance, is associated with altered stress responses and behaviors such as anxiety and depression.
Current literature on the cellular and molecular mechanisms of gut hormones and microbiota is limited and primarily based on animal studies.

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The intestine plays numerous roles in the normal physiology of our body. Gut-brain axis (GBA) is a complex communication network linking the gastrointestinal (GI) tract and central nervous system (CNS). This bidirectional system integrates endocrine, neural, and immune signals, impacting host metabolism and cognition. The gut microbiota, a critical component of the GBA, significantly impacts gut hormones, neurotransmission, neural development, and other components of gut-brain-axis. The microbiota-gut-brain axis facilitates communication via metabolites such as short chain fatty acids (SCFAs), and neurotransmitters such as dopamine, γ-amino butyric acid (GABA) and serotonin. The microbiota influences gut peptide production, including ghrelin, glucagon like pepetide-1 (GLP-1), serotonin, and cholecystokinin (CCK), thereby modulating nutrient absorption and immune responses. Gut hormones such as ghrelin, CCK, GLP-1, gastric inhibitory peptide (GIP), serotonin (5-HT), neurotensin, peptide YY (PYY) and melatonin play key roles in the GBA. These hormones play several roles including modulation of appetite and satiety, metabolism of nutrients such as lipid and glucose, insulin and glucagon secretion, and influence on gut inflammation, mood, learning and cognition. The interaction between gut microbiota and these hormones underscores their role in maintaining gut-brain homeostasis. Dysbiosis, or microbial imbalance, is linked to altered stress responses, anxiety, and depressive behaviors, highlighting the therapeutic potential of microbiota modulation. Despite the significant roles of gut hormones and microbiota in the GBA, literature on their cellular and molecular mechanisms is limited, and often based on animal models. This review synthesizes current understanding of hormones secreted by the intestine, their physiological effects and the cellular and molecular mechanisms of action underlying these effects, with a focus on their roles in the GBA. By elucidating these complex relationships, the review aims to advance research and clinical applications, offering insights into gastrointestinal and systemic health.

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