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12 pages, 947 KiB

Open AccessArticle

Unveiling the Connection between Microbiota and Depressive Disorder through Machine Learning

by Irina Y. Angelova, Alexey S. Kovtun, Olga V. Averina, Tatiana A. Koshenko and Valery N. Danilenko

Int. J. Mol. Sci. 2023, 24(22), 16459; https://doi.org/10.3390/ijms242216459 - 17 Nov 2023

Viewed by 1057

Abstract

In the last few years, investigation of the gut–brain axis and the connection between the gut microbiota and the human nervous system and mental health has become one of the most popular topics. Correlations between the taxonomic and functional changes in gut microbiota [...] Read more.

In the last few years, investigation of the gut–brain axis and the connection between the gut microbiota and the human nervous system and mental health has become one of the most popular topics. Correlations between the taxonomic and functional changes in gut microbiota and major depressive disorder have been shown in several studies. Machine learning provides a promising approach to analyze large-scale metagenomic data and identify biomarkers associated with depression. In this work, machine learning algorithms, such as random forest, elastic net, and You Only Look Once (YOLO), were utilized to detect significant features in microbiome samples and classify individuals based on their disorder status. The analysis was conducted on metagenomic data obtained during the study of gut microbiota of healthy people and patients with major depressive disorder. The YOLO method showed the greatest effectiveness in the analysis of the metagenomic samples and confirmed the experimental results on the critical importance of a reduction in the amount of Faecalibacterium prausnitzii for the manifestation of depression. These findings could contribute to a better understanding of the role of the gut microbiota in major depressive disorder and potentially lead the way for novel diagnostic and therapeutic strategies. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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42 pages, 6733 KiB

Open AccessArticle

Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study

by Birna Asbjornsdottir, Snaevar Sigurdsson, Alba Miranda-Ribera, Maria Fiorentino, Takumi Konno, Jinggang Lan, Larus S. Gudmundsson, Magnus Gottfredsson, Bertrand Lauth, Bryndis Eva Birgisdottir and Alessio Fasano

Int. J. Mol. Sci. 2023, 24(19), 14730; https://doi.org/10.3390/ijms241914730 - 29 Sep 2023

Cited by 2 | Viewed by 1665

Abstract

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various [...] Read more.

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013). Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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16 pages, 1942 KiB

Open AccessArticle

Bioelectrical State of Bacteria Is Linked to Growth Dynamics and Response to Neurotransmitters: Perspectives for the Investigation of the Microbiota–Brain Axis

by David Muñoz-Rodríguez, Marwane Bourqqia-Ramzi, Maria Teresa García-Esteban, Antonio Murciano-Cespedosa, Alejandro Vian, Juan Lombardo-Hernández, Pablo García-Pérez, Francisco Conejero, Álvaro Mateos González, Stefano Geuna and Celia Herrera-Rincon

Int. J. Mol. Sci. 2023, 24(17), 13394; https://doi.org/10.3390/ijms241713394 - 29 Aug 2023

Viewed by 1686

Abstract

Inter-cellular communication is mediated by a sum of biochemical, biophysical, and bioelectrical signals. This might occur not only between cells belonging to the same tissue and/or animal species but also between cells that are, from an evolutionary point of view, far away. The [...] Read more.

Inter-cellular communication is mediated by a sum of biochemical, biophysical, and bioelectrical signals. This might occur not only between cells belonging to the same tissue and/or animal species but also between cells that are, from an evolutionary point of view, far away. The possibility that bioelectrical communication takes place between bacteria and nerve cells has opened exciting perspectives in the study of the gut microbiota–brain axis. The aim of this paper is (i) to establish a reliable method for the assessment of the bioelectrical state of two bacterial strains: Bacillus subtilis (B. subtilis) and Limosilactobacillus reuteri (L. reuteri); (ii) to monitor the bacterial bioelectrical profile throughout its growth dynamics; and (iii) to evaluate the effects of two neurotransmitters (glutamate and γ-aminobutyric acid-GABA) on the bioelectrical signature of bacteria. Our results show that membrane potential (Vmem) and the proliferative capacity of the population are functionally linked in B. subtilis in each phase of the cell cycle. Remarkably, we demonstrate that bacteria respond to neural signals by changing Vmem properties. Finally, we show that Vmem changes in response to neural stimuli are present also in a microbiota-related strain L. reuteri. Our proof-of-principle data reveal a new methodological approach for the better understanding of the relation between bacteria and the brain, with a special focus on gut microbiota. Likewise, this approach will open exciting perspectives in the study of the inter-cellular mechanisms which regulate the bi-directional communication between bacteria and neurons and, ultimately, for designing gut microbiota–brain axis-targeted treatments for neuropsychiatric diseases. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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20 pages, 2063 KiB

Open AccessArticle

Modulation of Gut Microbiome in Ecstasy/MDMA-Induced Behavioral and Biochemical Impairment in Rats and Potential of Post-Treatment with Anacyclus pyrethrum L. Aqueous Extract to Mitigate Adverse Effects

by Abdelmounaim Baslam, Abdelfatah Aitbaba, Asmae Lamrani Hanchi, Zakaria Tazart, Rachida Aboufatima, Nabila Soraa, Mohamed Ait-El-Mokhtar, Samia Boussaa, Marouane Baslam and Abderrahman Chait

Int. J. Mol. Sci. 2023, 24(10), 9086; https://doi.org/10.3390/ijms24109086 - 22 May 2023

Cited by 8 | Viewed by 2750

Abstract

The use of illicit substances continues to pose a substantial threat to global health, affecting millions of individuals annually. Evidence suggests the existence of a ‘brain–gut axis’ as the involving connection between the central nervous system and gut microbiome (GM). Dysbiosis of the [...] Read more.

The use of illicit substances continues to pose a substantial threat to global health, affecting millions of individuals annually. Evidence suggests the existence of a ‘brain–gut axis’ as the involving connection between the central nervous system and gut microbiome (GM). Dysbiosis of the GM has been associated with the pathogenesis of various chronic diseases, including metabolic, malignant, and inflammatory conditions. However, little is currently known about the involvement of this axis in modulating the GM in response to psychoactive substances. In this study, we investigated the effect of MDMA (3,4-methylenedioxymethamphetamine, “Ecstasy”)-dependence on the behavioral and biochemical responses, and the diversity and abundance of the gut microbiome in rats post-treated (or not) with aqueous extract of Anacyclus pyrethrum (AEAP), which has been reported to exhibit anticonvulsant activity. The dependency was validated using the conditioned place preference (CPP) paradigm, behavioral, and biochemical tests, while the gut microbiota was identified using matrix-assisted laser desorption ionization–time of flight mass spectrometry (MALDI-TOF MS). The CPP and behavioral tests confirmed the presence of MDMA withdrawal syndrome. Interestingly, treatment with AEAP led to a compositional shift in the GM compared to the MDMA-treated rats. Specifically, the AEAP group yielded a higher relative abundance of Lactobacillus and Bifidobacter, while animals receiving MDMA had higher levels of E. coli. These findings suggest that A. pyrethrum therapy may directly modulate the gut microbiome, highlighting a potential target for regulating and treating substance use disorders. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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11 pages, 1126 KiB

Open AccessCommunication

Gut Microbiota Metabolites Differentially Release Gliotransmitters from the Cultured Human Astrocytes: A Preliminary Report

by Michał Seweryn Karbownik, Paulina Sokołowska and Edward Kowalczyk

Int. J. Mol. Sci. 2023, 24(7), 6617; https://doi.org/10.3390/ijms24076617 - 01 Apr 2023

Cited by 2 | Viewed by 1464

Abstract

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic [...] Read more.

Butyrate and indole-3-propionic acid represent the CNS-available gut microbiota metabolites exhibiting potentially beneficial effects on human brain function and being tested as antidepressants. Astrocytes represent one of the putative targets for the gut metabolites; however, the mechanism of action of butyrate and indole-3-propionic acid is not well understood. In order to test this mechanism, a human astrocyte cell-line culture was treated with the compounds or without them, and the supernatants were collected for the analysis of ATP and glutamate gliotransmitter release with the use of luminescent and fluorescent methods, respectively. A 10-min incubation of astrocytes with 1–5 mM butyrate increased the ATP gliotransmitter release by 78% (95%CI: 45–119%), p < 0.001. The effect was found to be mediated by the cytosolic Ca²⁺ mobilization. Both 10-min and 24-h treatments with indole-3-propionic acid produced no significant effects on the release of gliotransmitters. The results for glutamate release were inconclusive due to a specific glutamate release pattern discovered in the tested model. This preliminary report of butyrate-induced ATP gliotransmitter release appears to provide a novel mechanistic explanation for the beneficial effect of this gut microbiota metabolite on brain function; however, the results require further evaluation in more composed models. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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Review

Jump to: Research

23 pages, 1329 KiB

Open AccessReview

The Role of the Gut Microbiota in Anorexia Nervosa in Children and Adults—Systematic Review

by Dana-Teodora Anton-Păduraru, Felicia Trofin, Eduard Vasile Nastase, Radu Stefan Miftode, Ionela-Larisa Miftode, Mioara Florentina Trandafirescu, Elena Cojocaru, Elena Țarcă, Dana Elena Mindru and Olivia Simona Dorneanu

Int. J. Mol. Sci. 2024, 25(1), 41; https://doi.org/10.3390/ijms25010041 - 19 Dec 2023

Viewed by 1130

Abstract

Among the factors incriminated in the appearance of eating disorders, intestinal microbiota has recently been implicated. Now there is evidence that the composition of gut microbiota is different in anorexia nervosa. We gathered many surveys on the changes in the profile of gut [...] Read more.

Among the factors incriminated in the appearance of eating disorders, intestinal microbiota has recently been implicated. Now there is evidence that the composition of gut microbiota is different in anorexia nervosa. We gathered many surveys on the changes in the profile of gut microbiota in patients with anorexia nervosa. This review comprehensively examines the contemporary experimental evidence concerning the bidirectional communication between gut microbiota and the brain. Drawing from recent breakthroughs in this area of research, we propose that the gut microbiota significantly contributes to the intricate interplay between the body and the brain, thereby contributing to overall healthy homeostasis while concurrently impacting disease risk, including anxiety and mood disorders. Particular attention is devoted to elucidating the structure and functional relevance of the gut microbiota in the context of Anorexia Nervosa. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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16 pages, 1165 KiB

Open AccessReview

Our Mental Health Is Determined by an Intrinsic Interplay between the Central Nervous System, Enteric Nerves, and Gut Microbiota

by Leon M. T. Dicks

Int. J. Mol. Sci. 2024, 25(1), 38; https://doi.org/10.3390/ijms25010038 - 19 Dec 2023

Viewed by 1681

Abstract

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. The gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid [...] Read more.

Bacteria in the gut microbiome play an intrinsic part in immune activation, intestinal permeability, enteric reflex, and entero-endocrine signaling. The gut microbiota communicates with the central nervous system (CNS) through the production of bile acids, short-chain fatty acids (SCFAs), glutamate (Glu), γ-aminobutyric acid (GABA), dopamine (DA), norepinephrine (NE), serotonin (5-HT), and histamine. A vast number of signals generated in the gastrointestinal tract (GIT) reach the brain via afferent fibers of the vagus nerve (VN). Signals from the CNS are returned to entero-epithelial cells (EES) via efferent VN fibers and communicate with 100 to 500 million neurons in the submucosa and myenteric plexus of the gut wall, which is referred to as the enteric nervous system (ENS). Intercommunications between the gut and CNS regulate mood, cognitive behavior, and neuropsychiatric disorders such as autism, depression, and schizophrenia. The modulation, development, and renewal of nerves in the ENS and changes in the gut microbiome alter the synthesis and degradation of neurotransmitters, ultimately influencing our mental health. The more we decipher the gut microbiome and understand its effect on neurotransmission, the closer we may get to developing novel therapeutic and psychobiotic compounds to improve cognitive functions and prevent mental disorders. In this review, the intricate control of entero-endocrine signaling and immune responses that keep the gut microbiome in a balanced state, and the influence that changing gut bacteria have on neuropsychiatric disorders, are discussed. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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31 pages, 2425 KiB

Open AccessReview

Major Depressive Disorder and Gut Microbiota: Role of Physical Exercise

by Pedro Borges de Souza, Laura de Araujo Borba, Louise Castro de Jesus, Ana Paula Valverde, Joana Gil-Mohapel and Ana Lúcia S. Rodrigues

Int. J. Mol. Sci. 2023, 24(23), 16870; https://doi.org/10.3390/ijms242316870 - 28 Nov 2023

Cited by 4 | Viewed by 2134

Abstract

Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex interaction between environmental and genetic factors. In recent years, the role of the gut microbiota in brain [...] Read more.

Major depressive disorder (MDD) has a high prevalence and is a major contributor to the global burden of disease. This psychiatric disorder results from a complex interaction between environmental and genetic factors. In recent years, the role of the gut microbiota in brain health has received particular attention, and compelling evidence has shown that patients suffering from depression have gut dysbiosis. Several studies have reported that gut dysbiosis-induced inflammation may cause and/or contribute to the development of depression through dysregulation of the gut–brain axis. Indeed, as a consequence of gut dysbiosis, neuroinflammatory alterations caused by microglial activation together with impairments in neuroplasticity may contribute to the development of depressive symptoms. The modulation of the gut microbiota has been recognized as a potential therapeutic strategy for the management of MMD. In this regard, physical exercise has been shown to positively change microbiota composition and diversity, and this can underlie, at least in part, its antidepressant effects. Given this, the present review will explore the relationship between physical exercise, gut microbiota and depression, with an emphasis on the potential of physical exercise as a non-invasive strategy for modulating the gut microbiota and, through this, regulating the gut–brain axis and alleviating MDD-related symptoms. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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31 pages, 2786 KiB

Open AccessReview

Microbiota in Autism Spectrum Disorder: A Systematic Review

by Zuzanna Lewandowska-Pietruszka, Magdalena Figlerowicz and Katarzyna Mazur-Melewska

Int. J. Mol. Sci. 2023, 24(23), 16660; https://doi.org/10.3390/ijms242316660 - 23 Nov 2023

Cited by 1 | Viewed by 1719

Abstract

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by several core symptoms: restricted interests, communication difficulties, and impaired social interactions. Many ASD children experience gastrointestinal functional disorders, impacting their well-being. Emerging evidence suggests that a gut microbiota imbalance may exacerbate core [...] Read more.

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition characterized by several core symptoms: restricted interests, communication difficulties, and impaired social interactions. Many ASD children experience gastrointestinal functional disorders, impacting their well-being. Emerging evidence suggests that a gut microbiota imbalance may exacerbate core and gastrointestinal symptoms. Our review assesses the gut microbiota in children with ASD and interventions targeting microbiota modulation. The analysis of forty-four studies (meta-analyses, reviews, original research) reveals insights into the gut microbiota–ASD relationship. While specific microbiota alterations are mixed, some trends emerge. ASD children exhibit increased Firmicutes (36–81%) and Pseudomonadota (78%) and decreased Bacteroidetes (56%). The Bacteroidetes to Firmicutes ratio tends to be lower (56%) compared to children without ASD, which correlates with behavioral and gastrointestinal abnormalities. Probiotics, particularly Lactobacillus, Bifidobacterium, and Streptococcus strains, show promise in alleviating behavioral and gastrointestinal symptoms (66%). Microbiota transfer therapy (MTT) seems to have lasting benefits for the microbiota and symptoms in one longitudinal study. Prebiotics can potentially help with gastrointestinal and behavioral issues, needing further research for conclusive efficacy due to different interventions being used. This review highlights the gut microbiota–ASD interplay, offering potential therapeutic avenues for the gut–brain axis. However, study heterogeneity, small sample sizes, and methodological variations emphasize the need for comprehensive, standardized research. Future investigations may unveil complex mechanisms linking the gut microbiota to ASD, ultimately enhancing the quality of life for affected individuals. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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19 pages, 707 KiB

Open AccessReview

Intermittent Fasting as a Potential Therapeutic Instrument for Major Depression Disorder: A Systematic Review of Clinical and Preclinical Studies

by Laís Murta, Daniela Seixas, Luana Harada, Rodolfo Furlan Damiano and Marcus Zanetti

Int. J. Mol. Sci. 2023, 24(21), 15551; https://doi.org/10.3390/ijms242115551 - 25 Oct 2023

Cited by 1 | Viewed by 2841

Abstract

Recent studies have reported positive effects of Intermittent Fasting (IF) on metabolic parameters, cognition, and mood. However, regarding depressive symptoms, the effect of IF is not clear. The purpose of this review was to assess the available evidence on IF interventions for depression [...] Read more.

Recent studies have reported positive effects of Intermittent Fasting (IF) on metabolic parameters, cognition, and mood. However, regarding depressive symptoms, the effect of IF is not clear. The purpose of this review was to assess the available evidence on IF interventions for depression in both clinical and preclinical studies. Of the 23 included studies, 15 were performed on humans and 8 on animal models. The studies on rodents suggested that IF acts as a circadian regulator, improving neurotransmitter availability and increasing the levels of neurotrophic factors in the brain. However, the investigations on humans mainly evaluated healthy volunteers and showed a great heterogeneity regarding both the IF regimen studied and the observed effects on mood. Most available clinical trials have specific limitations, such as small sample sizes and uncontrolled designs. A comprehensive systematic review was conducted on five databases, PubMed, Cochrane, the Central Register of Controlled Trials, Web of Science databases, BVS and Scopus, identifying 23 relevant studies up to 6 October 2022. IF has potentially relevant physiological effects for the treatment of mood disorders, but better designed studies and controlled evaluations are needed to evaluate its efficiency in the treatment of major depression. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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10 pages, 1355 KiB

Open AccessReview

Connecting Cryptococcal Meningitis and Gut Microbiome

by Yuanyuan Ma, Liang Yang, Mengna Jiang, Xinyuan Zhao and Peng Xue

Int. J. Mol. Sci. 2023, 24(17), 13515; https://doi.org/10.3390/ijms241713515 - 31 Aug 2023

Cited by 1 | Viewed by 1093

Abstract

Fungal pathogens of the Cryptococcus neoformans species complex (C. neoformans SC) are a major cause of fungal meningitis in immunocompromised individuals. As with other melanotic microorganisms associated with human diseases, the cell-wall-associated melanin of C. neoformans SC is a major virulence factor [...] Read more.

Fungal pathogens of the Cryptococcus neoformans species complex (C. neoformans SC) are a major cause of fungal meningitis in immunocompromised individuals. As with other melanotic microorganisms associated with human diseases, the cell-wall-associated melanin of C. neoformans SC is a major virulence factor that contributes to its ability to evade host immune responses. The levels of melanin substrate and the regulation of melanin formation could be influenced by the microbiota–gut–brain axis. Moreover, recent studies show that C. neoformans infections cause dysbiosis in the human gut microbiome. In this review, we discuss the potential association between cryptococcal meningitis and the gut microbiome. Additionally, the significant potential of targeting the gut microbiome in the diagnosis and treatment of this debilitating disease is emphasized. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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28 pages, 1193 KiB

Open AccessReview

Microbial Reprogramming in Obsessive–Compulsive Disorders: A Review of Gut–Brain Communication and Emerging Evidence

by Ghizlane Bendriss, Ross MacDonald and Clare McVeigh

Int. J. Mol. Sci. 2023, 24(15), 11978; https://doi.org/10.3390/ijms241511978 - 26 Jul 2023

Cited by 3 | Viewed by 3619

Abstract

Obsessive–compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the [...] Read more.

Obsessive–compulsive disorder (OCD) is a debilitating mental health disorder characterized by intrusive thoughts (obsessions) and repetitive behaviors (compulsions). Dysbiosis, an imbalance in the gut microbial composition, has been associated with various health conditions, including mental health disorders, autism, and inflammatory diseases. While the exact mechanisms underlying OCD remain unclear, this review presents a growing body of evidence suggesting a potential link between dysbiosis and the multifaceted etiology of OCD, interacting with genetic, neurobiological, immunological, and environmental factors. This review highlights the emerging evidence implicating the gut microbiota in the pathophysiology of OCD and its potential as a target for novel therapeutic approaches. We propose a model that positions dysbiosis as the central unifying element in the neurochemical, immunological, genetic, and environmental factors leading to OCD. The potential and challenges of microbial reprogramming strategies, such as probiotics and fecal transplants in OCD therapeutics, are discussed. This review raises awareness of the importance of adopting a holistic approach that considers the interplay between the gut and the brain to develop interventions that account for the multifaceted nature of OCD and contribute to the advancement of more personalized approaches. Full article

(This article belongs to the Special Issue Recent Research of Gut Microbiota-Brain Axis and Neurons in Psychiatric Disorders)

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