{"id":22619,"date":"2026-03-12T10:36:15","date_gmt":"2026-03-12T09:36:15","guid":{"rendered":"https:\/\/www.biolife-publisher.it\/ejnd\/?p=22619"},"modified":"2026-03-12T10:36:58","modified_gmt":"2026-03-12T09:36:58","slug":"the-relationship-between-intestinal-microbiota-and-the-central-nervous-system","status":"publish","type":"post","link":"https:\/\/www.biolife-publisher.it\/ejnd\/2026\/03\/12\/the-relationship-between-intestinal-microbiota-and-the-central-nervous-system\/","title":{"rendered":"THE RELATIONSHIP BETWEEN INTESTINAL MICROBIOTA AND THE CENTRAL NERVOUS SYSTEM"},"content":{"rendered":"

C. di Lorenzo*<\/sup><\/p>\n

Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy.<\/p>\n

*Correspondence to<\/em>:
\nCherubino di Lorenzo, MD,
\nDepartment of Medico-Surgical Sciences and Biotechnologies,
\nSapienza University of Rome,
\nPolo Pontino, 04100 Latina, Italy.
\ne-mail: cherub@inwind.it<\/p>\n\n\n\n
Received: 01 May, 2025
\nAccepted: 10 June, 2025\"adobe-pdf-download-icon\"<\/a><\/td>\n		ISSN 2279-5855 print
\nISSN 2974-6345 online. Copyright \u00a9 by BIOLIFE 2025
\nThis publication and\/or article is for individual use only and may not be further reproduced without written permission from the copyright holder. Unauthorized reproduction may result in financial and other penalties. Disclosure: All authors report no conflicts of interest relevant to this article.<\/td>\n<\/tr>\n<\/tbody>\n<\/table>\n

ABSTRACT<\/strong><\/p>\n

There are bidirectional interactions between the intestine and the central nervous system (CNS), both in the case of pathologies and in health. The human intestine hosts many types of microorganisms which can regulate intestinal hemostasis and modulate intestinal pathologies, including inflammatory ones. The CNS regulates various intestinal functions such as blood circulation, motility, and secretion. Psychological stress can aggravate colon diseases, such as ulcerative colitis. The intestine can signal an inflammatory state of the mucosa, pain, and nociceptive responses to the CNS. However, the exact mechanism that regulates the relationship between intestinal microbiota and the brain is still unclear. The pathogenic microorganisms that harbor the intestine engage in crosstalk with the primary afferent neurons of the intestinal tissue. The perception of intestinal stimuli is modulated by the CNS with the involvement of the sympathetic and parasympathetic systems. The microbiota interacts with the intestinal effector mechanisms and with the afferent pathways of the stomach and intestine, creating a bidirectional system that goes from the intestine to the brain and vice-versa. Studying these interactions can better clarify the pathogenic mechanisms that underlie various inflammatory intestinal diseases.<\/p>\n

KEYWORDS:<\/strong> Brain, intestine, microbiota, CNS, bidirectional communication, gut-brain axis, immune system<\/em><\/p>\n

\u00a0<\/strong><\/p>\n

INTRODUCTION<\/strong><\/p>\n

 <\/p>\n

The intestine and the central nervous system (CNS) are engaged in bidirectional interaction, both in the case of pathologies and homeostasis. Pathogenic microorganisms that harbor the intestine also participate in this crosstalk with the nervous system and can affect afferent neurons to influence gut motility, secretion, and pain perception.<\/p>\n

The gut microbiota plays an important role in the physiology of host organs, including the brain, and communicates with the CNS through molecular and cellular mechanisms (1-4). The gut-brain axis is a bidirectional crosstalk system between the two organs, regulated by the immune system, the central and enteric nervous systems, and the endocrine system (3). Communication occurs through neural, molecular, immune, and metabolic pathways.<\/p>\n

 <\/p>\n

DISCUSSION<\/strong><\/p>\n

 <\/p>\n

The CNS communicates primarily with microbiota through neuronal pathways and the vagus nerve (4). At the cellular level, bacteria produce metabolites such as GABA, which communicate with the CNS (5). The metabolites activate enteric neurons and enteroendocrine cells, which transmit signals to the CNS through the vagus nerve (4). At the molecular level, communication between the gut and CNS occurs through neurotransmitters such as serotonin produced in the gut, GABA, and dopamine (2). These reactions activate various receptors, such as G protein-coupled receptors and ionotropic receptors, which affect anxiety, mood, and stress (6). The metabolic pathway is activated by microbial metabolites such as short-chain fatty acids, butyrate, propionate, and acetate (7). At the molecular level, these molecules bind to GPR41\/GPR43 receptors and inhibit histone deacetylases that modulate epigenetics (6). Microbial metabolites strengthen the blood-brain barrier (BBB) by modulating microglia, neuroinflammation, and neuroplasticity (8).<\/p>\n

The main tryptophan metabolites, including serotonin, melatonin, niacin (vitamin B3), and kynurenine derivatives, have effects on the regulation of neurotransmission and modulation of inflammatory tone in the CNS (9). The immune and inflammatory response in the brain is primarily triggered by microglia, with a cellular mechanism of dysbiosis that causes increased intestinal permeability known as leaky gut (8).\u00a0 This allows lipopolysaccharides (LPS) and microbial pathogen-associated molecular patterns (PAMPs) to pass through the tissues, activating a molecular mechanism involving Toll-like receptors (TLRs) and nod-like receptors (NLRs) (10).\u00a0 These latter molecules are important for the production of inflammatory cytokines produced by activated microglia, leading to neuroinflammation (11,12). The endocrine pathway is represented by the hypothalamic-pituitary-adrenal (HPA) axis, which involves a molecular mechanism in which stress plays a role, resulting in increased cortisol (13). The microbiota modulates the expression of glucocorticoid receptors in response to stress, alters neuronal maturation, and modifies behavioral responses (14).<\/p>\n

Abnormal functioning of gut microbiota is connected to abnormal immune responses with altered production of inflammatory cytokines and is linked to autoimmune\/immune-mediuated diseases such as rheumatoid arthritis (15,16) (Fig.1).<\/p>\n

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Fig. 1.<\/strong> Alterations in gastrointestinal microbiota activate inflammatory cytokines which stimulate microglia, causing alterations in mood and cognition with subsequent alterations of the microbiota. These reactions are bidirectional components of the gut-brain axis.<\/em><\/p>\n

 <\/p>\n

CONCLUSIONS<\/strong><\/p>\n

 <\/p>\n

At the molecular level, the gut microbiota influences short-chain fatty acids, neurotransmitters, cytokines, and receptors, while at the cellular and systemic level, it is involved in the functions of enteric neurons, microglia, immune cells, the vagus nerve, HPA, and the BBB.<\/p>\n

 <\/p>\n

Conflict of interest <\/em><\/p>\n

The author declares that they have no conflict of interest.<\/p>\n

\u00a0<\/strong><\/p>\n

REFERENCES<\/strong><\/p>\n

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    C. di Lorenzo* Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy. *Correspondence to: Cherubino di Lorenzo,...<\/p>\n","protected":false},"author":1033,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":"","_members_access_role":[],"_members_access_error":""},"categories":[2784],"tags":[2813,965,2543,2814,456,2812,316],"class_list":["post-22619","post","type-post","status-publish","format-standard","hentry","category-ejnd-2025-vol-14-issue-n-2","tag-bidirectional-communication","tag-brain","tag-cns","tag-gut-brain-axis","tag-immune-system","tag-intestine","tag-microbiota"],"acf":[],"yoast_head":"\nTHE RELATIONSHIP BETWEEN INTESTINAL MICROBIOTA AND THE CENTRAL NERVOUS SYSTEM - European Journal of Neurodegenerative Diseases<\/title>\n<meta name=\"description\" content=\"Founded in 1987, BIOLIFE is an independent, academic publisher of innovative, high-quality content. 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