Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions

The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highligh...

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Main Authors: Ilinca Savulescu-Fiedler, Serban-Nicolae Benea, Constantin Căruntu, Andreea-Simona Nancoff, Corina Homentcovschi, Sandica Bucurica
Format: Article
Language:English
Published: MDPI AG 2025-06-01
Series:Current Issues in Molecular Biology
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Online Access:https://www.mdpi.com/1467-3045/47/7/489
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author Ilinca Savulescu-Fiedler
Serban-Nicolae Benea
Constantin Căruntu
Andreea-Simona Nancoff
Corina Homentcovschi
Sandica Bucurica
author_facet Ilinca Savulescu-Fiedler
Serban-Nicolae Benea
Constantin Căruntu
Andreea-Simona Nancoff
Corina Homentcovschi
Sandica Bucurica
author_sort Ilinca Savulescu-Fiedler
collection DOAJ
description The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions.
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spelling doaj-art-41cd44ce7be34811a90cbdadaa4f35352025-08-20T03:58:26ZengMDPI AGCurrent Issues in Molecular Biology1467-30371467-30452025-06-0147748910.3390/cimb47070489Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System InteractionsIlinca Savulescu-Fiedler0Serban-Nicolae Benea1Constantin Căruntu2Andreea-Simona Nancoff3Corina Homentcovschi4Sandica Bucurica5Department of Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Infectious Diseases, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Physiology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Gastroenterology, Bucharest Emergency Clinical Hospital, 014461 Bucharest, RomaniaDepartment of Internal Medicine, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaDepartment of Gastroenterology, “Carol Davila” University of Medicine and Pharmacy, 050474 Bucharest, RomaniaThe gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions.https://www.mdpi.com/1467-3045/47/7/489gut-brain axismicrobiota-gut-brain axisenteric nervous systeminteroceptiongut feelingshort-chain fatty acids (SCFAs)
spellingShingle Ilinca Savulescu-Fiedler
Serban-Nicolae Benea
Constantin Căruntu
Andreea-Simona Nancoff
Corina Homentcovschi
Sandica Bucurica
Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
Current Issues in Molecular Biology
gut-brain axis
microbiota-gut-brain axis
enteric nervous system
interoception
gut feeling
short-chain fatty acids (SCFAs)
title Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
title_full Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
title_fullStr Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
title_full_unstemmed Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
title_short Rewiring the Brain Through the Gut: Insights into Microbiota–Nervous System Interactions
title_sort rewiring the brain through the gut insights into microbiota nervous system interactions
topic gut-brain axis
microbiota-gut-brain axis
enteric nervous system
interoception
gut feeling
short-chain fatty acids (SCFAs)
url https://www.mdpi.com/1467-3045/47/7/489
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