Bidirectional Communication Research Articles

The gut microbiome and the brain.

The importance of the gut microbiome for human health and well-being is generally accepted, and elucidating the signaling pathways between the gut microbiome and the host offers novel mechanistic insight into the (patho)physiology and multifaceted aspects of healthy aging and human brain functions. The gut microbiome is tightly linked with the nervous system, and gut microbiota are increasingly emerging as important regulators of emotional and cognitive performance. They send and receive signals for the bidirectional communication between gut and brain via immunological, neuroanatomical, and humoral pathways. The composition of the gut microbiota and the spectrum of metabolites and neurotransmitters that they release changes with increasing age, nutrition, hypoxia, and other pathological conditions. Changes in gut microbiota (dysbiosis) are associated with critical illnesses such as cancer, cardiovascular, and chronic kidney disease but also neurological, mental, and pain disorders, as well as chemotherapies and antibiotics affecting brain development and function. Dysbiosis and a concomitant imbalance of mediators are increasingly emerging both as causes and consequences of diseases affecting the brain. Understanding the microbiota's role in the pathogenesis of these disorders will have major clinical implications and offer new opportunities for therapeutic interventions.

Immune Response in Traumatic Brain Injury.

This review aims to comprehensively examine the immune response following traumatic brain injury (TBI) and how its disruption can impact healing and recovery. The immune response is now considered a key element in the pathophysiology of TBI, with consequences far beyond the acute phase after injury. A delicate equilibrium is crucial for a healthy recovery. When this equilibrium is disrupted, chronic inflammation and immune imbalance can lead to detrimental effects on survival and disability. Globally, traumatic brain injury (TBI) imposes a substantial burden in terms of both years of life lost and years lived with disability. Although its epidemiology exhibits dynamic trends over time and across regions, TBI disproportionally affects the younger populations, posing psychosocial and financial challenge for communities and families. Following the initial trauma, the primary injury is succeeded by an inflammatory response, primarily orchestrated by the innate immune system. The inflammasome plays a pivotal role during this stage, catalyzing both programmed cell death pathways and the up-regulation of inflammatory cytokines and transcription factors. These events trigger the activation and differentiation of microglia, thereby intensifying the inflammatory response to a systemic level and facilitating the migration of immune cells and edema. This inflammatory response, initially originated in the brain, is monitored by our autonomic nervous system. Through the vagus nerve and adrenergic and cholinergic receptors in various peripheral lymphoid organs and immune cells, bidirectional communication and regulation between the immune and nervous systems is established.

Lessons from a participatory community cricket breeding project in Vientiane Province, Lao PDR

Abstract Edible insect production is a key tool for sustainable development and global food security, but its social dimensions and the organisation of farming operations remain understudied. Crickets are among the most recognised edible insects for farming and offer appealing development opportunities for Lao PDR – a Southeast Asian country whose cricket farming sector has lagged behind neighbouring Thailand and which continues to experience challenging economic and food security conditions. Concerning these sustainable development and research priorities, this paper presents the case study analysis of a service evaluation of Cricket Lao Farm, which implemented a project on the distributed (off-site) production of crickets among local community members. Data collection took place from September to November 2023 and included a survey with 30 participants complemented by qualitative information from discussion groups, home visits, informal conversations, and project documentation. While small-scale farming operations ended within a year due to widespread cricket mortality of unknown cause, community-based cricket farming was in principle profitable and demonstrated strong development potential and local relevance. Furthermore, most of the community-based farmers were motivated and interested in resuming operations in the future. The analysis of this case offers important lessons for further development of the cricket farming sector in Lao PDR, highlighting the challenges of the Western social enterprise model in a development setting, the need to actively manage participation, and to develop an understanding of local community structures before commencing operations. To ensure future success, projects should include robust monitoring and evaluation plans; regular and bidirectional communication between community members and the central farm; co-development of breeding strategies, response plans, and good animal husbandry practices; and community engagement activities involving local schools.

Convergence of Neuroinflammation, Microbiota, and Parkinson's Disease: Therapeutic Insights and Prospects.

Parkinson's disease (PD) is a complex neurodegenerative disorder. Recent evidence reveals connections between neuroinflammatory processes and intestinal microbiota alterations in the progression of this pathology. This comprehensive review explores the intricate relationships between them, highlighting their combined impact on PD. Neuroinflammation, characterized by immune activation in the central nervous system, is increasingly acknowledged as a critical factor in the development of PD. Concurrently, alterations in the gut microbiota composition have been linked to PD, suggesting a potential modulatory role in disease progression. Thus, bidirectional communication along the gut-brain axis has become pivotal in comprehending the pathogenesis of PD. Furthermore, we explore emerging therapeutic strategies that target these interconnected pathways, providing insights into potential avenues for PD treatment. The elucidation of these intricate relationships establishes a promising foundation for innovative therapeutic strategies aimed at altering disease progression and improving the quality of life for individuals affected by PD.

Managing a 4000-participant cohort with a novel mobile app: data from the RisCoin study in Germany

Abstract Issue RisCoin, a prospective monocentric longitudinal observational study, aimed to identify risk factors for COVID-19 vaccine failure. Secondary aim is to monitor symptoms, SARS-CoV-2 infection, vaccination status of 3816 enrolled healthcare workers (HCW) and 180 patients with inflammatory bowel disease (IBD). Since the LMU University Hospital Munich served both as study sponsor and employer of the HCW, a secured approach was required. Description of the solution Participants accessed the study app (CentraXX, KAIROS GmbH, Germany) via pseudonymized Contact-ID with irreversible anonymization after 6 months. Key app features were the serological results report, bidirectional messaging, and weekly survey for self-reported data on vaccinations, infections, and symptoms. Active app use was defined as submitting >1 weekly survey during the study period 10.2021-12.2022. Results Over 15 months, our study team maintained 1964 two-way communications with 958 participants via the app. Of 3979 participants with app access, 3622 (91%) were active users, 2606 (65%) submitted 1 to 11 surveys, 1016 (26%) made ≥12 submissions (P75, “frequent users”). Frequent users were more likely to be IBD patients (p = 0.001), female (p < 0.001), aged 60 or older (p < 0.001). Staff in administration and nurses were more likely to be frequent users compared to physicians (p < 0.001). Main problems included the initial operational system disparities resulting in app crashes and continuous need for app reactivation. Both led to loss of active participants and required substantial staff resources to onboard and support participants during the study. Lessons The study app enabled secure, flexible, bidirectional communication with all participants. Despite technical issues, the majority actively used the app and provided valuable longitudinal data through weekly survey submissions. Key messages • A study-specific app provides a flexible and secure bidirectional anonymous communication for the study team and participants. • Adherence to app-based communication and data collection for pandemic monitoring was particularly high among patients, nurses and administrative staff.

Effects of Artemisia asiatica ex on Akkermansia muciniphila dominance for modulation of Alzheimer's disease in mice.

The gut microbiome influences neurological disorders through bidirectional communication between the gut and the brain, i.e., the gut-brain axis. Artemisia asiatica ex, an extract of Artemisia asiatica Nakai (Stillen®, DA-9601) has been reported to improve depression by increasing brain-derived neurotropic factor. Therefore, we hypothesized that DA-9601 can be a potential therapeutic candidate for Alzheimer's disease (AD) acting through the gut-brain axis. Four groups of Tg2576 mice were used as the animal model for AD: wild type mice (n = 6), AD mice (n = 6), and DA-9601-administered AD mice given dosages of 30mg/kg/day (DA_30mg; n = 6) or 100mg/kg/day (DA_100mg; n = 6). Microglial activation, blood‒brain barrier integrity, amyloid beta accumulation, cognitive behavior, and changes in the gut microbiome were analyzed. DA-9601 improved the cognitive behavior of mice (DA_30mg **p<0.01; DA_100mg **p<0.01) and reduced amyloid beta accumulation (DA_30mg ***p<0.001; DA_100mg **p<0.01). Increased Iba-1 and upregulation of claudin-5 (DA_30mg *p<0.05) and occludin (DA_30mg **p<0.01; DA_100mg ***p<0.001) indicated altered microglial activation and improved blood‒brain barrier integrity. Akkermansia muciniphila was dramatically increased by DA-9601 administration (DA_30mg 47%; DA_100mg 61%). DA-9601 improved AD pathology with Akkermansia muciniphila dominance in the gut microbiome in a mouse model of AD, inferring that DA-9601 can affect AD through the gut-brain axis.

Federated Deep Learning Model for False Data Injection Attack Detection in Cyber Physical Power Systems

Cyber-physical power systems (CPPS) integrate information and communication technology into conventional electric power systems to facilitate bidirectional communication of information and electric power between users and power grids. Despite its benefits, the open communication environment of CPPS is vulnerable to various security attacks. This paper proposes a federated deep learning-based architecture to detect false data injection attacks (FDIAs) in CPPS. The proposed work offers a strong, decentralized alternative with the ability to boost detection accuracy while maintaining data privacy, presenting a significant opportunity for real-world applications in the smart grid. This framework combines state-of-the-art machine learning and deep learning models, which are used in both centralized and federated learning configurations, to boost the detection of false data injection attacks in cyber-physical power systems. In particular, the research uses a multi-stage detection framework that combines several models, including classic machine learning classifiers like Random Forest and ExtraTrees Classifiers, and deep learning architectures such as Long Short-Term Memory (LSTM) and Gated Recurrent Unit (GRU). The results demonstrate that Bidirectional GRU and LSTM models with attention layers in a federated learning setup achieve superior performance, with accuracy approaching 99.8%. This approach enhances both detection accuracy and data privacy, offering a robust solution for FDIA detection in real-world smart grid applications.

Mouse enteric neurons control intestinal plasmacytoid dendritic cell function via serotonin-HTR7 signaling

Serotonergic neurons in the central nervous system control behavior and mood, but knowledge of the roles of serotonergic circuits in the regulation of immune homeostasis is limited. Here, we employ mouse genetics to investigate the functions of enteric serotonergic neurons in the control of immune responses and find that these circuits regulate IgA induction and boost host defense against oral, but not systemic Salmonella Typhimurium infection. Enteric serotonergic neurons promote gut-homing, retention and activation of intestinal plasmacytoid dendritic cells (pDC). Mechanistically, this neuro-immune crosstalk is achieved through a serotonin-5-HT receptor 7 (HTR7) signaling axis that ultimately facilitates the pDC-mediated differentiation of IgA+ B cells from IgD+ precursors in the gut. Single-cell RNA-seq data further reveal novel patterns of bidirectional communication between specific subsets of enteric neurons and lamina propria DC. Our findings thus reveal a close interplay between enteric serotonergic neurons and gut immune homeostasis that enhances mucosal defense.

Ex vivo and miniaturized in vitro models to study microbiota-gut-brain axis.

The microbiota-gut-brain axis involves complex bidirectional communication through neural, immune, and endocrine pathways. Microbial metabolites, such as short-chain fatty acids, influence gut motility and brain function by interacting with gut receptors and modulating hormone release. Additionally, microbial components such as lipopolysaccharides and cytokines can cross the gut epithelium and the blood-brain barrier, impacting immune responses and cognitive function. Ex vivo models, which preserve gut tissue and neural segments, offer insight into localized gut-brain communication by allowing for detailed study of nerve excitability in response to microbial signals, but they are limited in systemic complexity. Miniaturized in vitro models, including organ-on-chip platforms, enable precise control of the cellular environment and simulate complex microbiota-host interactions. These systems allow for the study of microbial metabolites, immune responses, and neuronal activity, providing valuable insights into gut-brain communication. Despite challenges such as replicating long-term biological processes and integrating immune and hormonal systems, advancements in bioengineered platforms are enhancing the physiological relevance of these models, offering new opportunities for understanding the mechanisms of the microbiota-gut-brain axis. This review aims to describe the ex vivo and miniaturized in vitro models which are used to mimic the in vivo conditions and facilitate more precise studies of gut brain communication.

The hepcidin-ferroportin axis modulates liver endothelial cell BMP expression to influence iron homeostasis in mice

AbstractThe liver hormone hepcidin regulates systemic iron homeostasis to provide enough iron for vital processes while limiting toxicity. Hepcidin acts by degrading its receptor ferroportin (encoded by Slc40a1) to decrease iron export to plasma. Iron controls hepcidin production in part by inducing liver endothelial cells (LECs) to produce bone morphogenetic proteins (BMPs) that activate hepcidin transcription in hepatocytes. Here, we used in vitro and in vivo models to investigate whether ferroportin contributes to LEC intracellular iron content to modulate BMP expression and, thereby, hepcidin. Quantitative proteomics of LECs from mice fed different iron diets demonstrated an inverse relationship between dietary iron and endothelial ferroportin expression. Slc40a1 knockdown primary mouse LECs and endothelial Slc40a1 knockout mice exhibited increased LEC iron and BMP ligand expression. Endothelial Slc40a1 knockout mice also exhibited altered systemic iron homeostasis with decreased serum and total liver iron but preserved erythropoiesis. Although endothelial Slc40a1 knockout mice had similar hepcidin expression to control mice, hepcidin levels were inappropriately high relative to iron levels. Moreover, when iron levels were equalized with iron treatment, hepcidin levels were higher in endothelial Slc40a1 knockout mice than in controls. Finally, LEC ferroportin levels were inversely correlated with hepcidin levels in multiple mouse models, and treatment of hepcidin-deficient mice with mini-hepcidin decreased LEC ferroportin expression. Overall, these data show that LEC ferroportin modulates LEC iron and consequently BMP expression to influence hepcidin production. Furthermore, LEC ferroportin expression is regulated by hepcidin, demonstrating a bidirectional communication between LECs and hepatocytes to orchestrate systemic iron homeostasis.

Probiotics and Other Supplements for Autism Spectrum Disorder (ASD): A Comprehensive Review

Introduction: Autism Spectrum Disorder (ASD) is a complex neurodevelopmental condition characterized by social interaction challenges, communication difficulties, and repetitive behaviors. While ASD lacks a cure, there is a growing interest in supplements, notably probiotics, for potential benefits. Probiotics are live microorganisms with health potential due to their role in the gut microbiome. Gut-brain axis is a bi-directional communication system that connects the gastrointestinal (GI) tract and the brain. Objective: This comprehensive review systematically searched scientific databases up to September 2023 to examine the use of supplements, particularly probiotics, in individuals with ASD. The review focused on addressing gut-related issues and improving behavior, speech, and overall well-being. Methods: A systematic search across databases such as PubMed, PsycINFO, and Cochrane library was conducted using keywords like "probiotics," "supplements," "ASD," "gut dysbiosis," and "therapeutic interventions." Studies meeting inclusion criteria, including clinical trials, observational studies, and case reports, were considered. Results: Several studies suggest that probiotics may improve behavior, brain activity, and eye contact in individuals with ASD by addressing gut dysbiosis. Lactobacillus reuteri and specific Bifidobacterium strains are recommended probiotics, but more research is needed to confirm their efficacy. This review also explores supplements like Vitamin B6, magnesium, Vitamin B12, Vitamin C, and Omega-3 fatty acids, which show potential in supporting speech and overall well-being in individuals with ASD. However, they are not a cure and should be used under professional guidance. The article also discusses supplements for adults with ASD, underlining the importance of consulting healthcare professionals before use and the necessity for further research to determine effectiveness and optimal dosages. Conclusion: Probiotics and supplements offer potential benefits for individuals with ASD, but they should be seen as complementary therapies rather than cures. A holistic approach, including medical supervision, therapy, and dietary considerations, is crucial for addressing the complex needs of individuals with ASD. Further research is necessary to uncover the precise mechanisms and therapeutic potential of these supplements in enhancing the lives of those with ASD. Categories: Neurology, Gastroenterology, Nutrition

Two critical membranes. How does the chloroplast envelope affect plant acclimation properties?

Chloroplasts play a pivotal role in the metabolism of leaf mesophyll cells, functioning as a cellular hub that orchestrates molecular reactions in response to environmental stimuli. These organelles contain complex protein machinery for energy conversion and are indispensable for essential metabolic pathways. Proteins located within the chloroplast envelope membranes facilitate bidirectional communication with the cell and connect essential pathways, thereby influencing acclimation processes to challenging environmental conditions such as temperature fluctuations and light intensity changes. Despite their importance, a comprehensive overview of the impact of envelope-located proteins during acclimation to environmental changes is lacking. Understanding the role of these proteins in acclimation processes could provide insights into enhancing stress tolerance under increasingly challenging environments. This review highlights the significance of envelope-located proteins in plant acclimation.

Prophylactic use of probiotics as an adjunctive treatment for ischemic stroke via the gut-spleen-brain axis

A growing body of research has focused on the role of spleen in orchestrating brain injury through the peripheral immune system following stroke, highlighting the brain-spleen axis as a potential target for mitigating neuronal damage during stroke. The gut microbiota plays a pivotal role in the bidirectional communication between the gut and the brain. Several studies have suggested that probiotic supplements hold promise as a strategic approach to maintaining a balanced intestinal microecology, reducing the apoptosis of intestinal epithelial cells, protecting the intestinal mucosal and blood–brain barrier (BBB), enhancing both intestinal and systemic immune functions, and thereby potentially affecting the pathogenesis and progression of ischemic stroke. In this study, we aimed to clarify the neuroprotective effects of supplementation with Lactobacillus, specifically Limosilactobacillus reuteri GMNL-89 (G89) and Lacticaseibacillus paracasei GMNL-133 (G133) on ischemic stroke and investigate how G89 and G133 modulate the communication mechanisms between the gut, brain, and spleen following ischemic stroke. We explored the neuroprotection and the underlying mechanisms of Lactobacillus supplementation in C57BL/6 mice subjected to permanent middle cerebral artery occlusion. Our results revealed that oral treatment with G89 or G133 alone, as well as oral administration combining G89 and G133, significantly decreased the infarct volume and improved the neurological function in mice with ischemic stroke. Moreover, G89 treatment alone preserved the tight junction integrity of gut barrier, while G133 alone and the combined treatment of G89 and G133 would significantly decreased the BBB permeability, and thereby significantly attenuated stroke-induced local and systemic inflammatory responses. Both G89 and G133 regulated cytotoxic T cells, and the balance between T helper 1 cells and T helper 2 cells in the spleen following ischemic stroke. Additionally, the combined administration of G89 and G133 improved the gut dysbiosis and significantly increased the concentration of short‐chain fatty acids. In conclusion, our findings suggest that G89 and G133 may be used as nutrient supplements, holding promise as a prospective approach to combat ischemic stroke by modulating the gut-spleen-brain axis.

Aggression shapes the gut microbiome; a study in rats.

The gut-brain axis is regarded as a bidirectional communication system that integrates signals from the gut microbiome into behavioral aspects and vice versa. The aim of the present study was to investigate the gut microbiome-behavior interaction in relation to aggression. For that, male rats from a group-housed colony were individually housed with a female to become territorial. Next, a coping strategy was assigned to them, by evaluating their aggression levels against an intruder, during the Resident-Intruder test (RI). To investigate if their microbiome would change as a consequence of the developed coping strategy, fecal samples were collected before and after the RI test. We found that the relative abundances of Ruminococcaceae UCG-5 and Gram-negative bacterium cTPY-13 in rats sampled before the RI test were negatively correlated with the aggression that was demonstrated during the RI test. After the RI test, several bacterial taxa could be assigned to each coping strategy, with Clostridium sensu stricto 1 being strongly associated with less aggressive rats and higher abundances of Bifidobacterium. Furthermore, the family of Lachnospiraceae was not only associated with more aggressive rats, but functional prediction analysis found it to be the main contributor of betaine reductase; an enzyme catalyzing betaine production that was indicative of aggressive rats. This amino acid derivative, which has been connected with higher energy and testosterone levels, could potentially explain the connection of Lachnospiraceae with demonstrated aggression. Overall, our data revealed that the gut bacterial communities are responsive to the imposed social challenge of building and defending territoriality in co-habitation with a female. At the same time, predisposing microbiome characteristics may have predictive value for the development of a coping strategy.

The role of reactive enteric glia-macrophage interactions in acute and chronic inflammation.

Enteric glia are a heterogeneous population of peripheral glia within the enteric nervous system and play pivotal roles in gut homeostasis, tissue integrity, coordination of motility, and intestinal immune responses. Under physiological conditions, they communicate with enteric neurons to control intestinal motility. In contrast, enteric glia undergo reactive changes in response to inflammatory signals during enteric neuroinflammation and participate in immune control. In this state, these glia are called reactive enteric glia, which promote cytokine and chemokine secretion and perpetuate immune cell recruitment, thereby affecting disease progression. Interestingly, reactive glia exhibit a huge plasticity and adapt to or shape the immune environment towards a resolving phenotype during inflammation and neuropathies. Recent studies revealed a bidirectional communication between enteric glia and resident and infiltrating immune cells under healthy conditions and in the context of inflammation-based intestinal disorders and neuropathies. While recent reviews give a superb general overview of enteric glial reactivity, we herein discuss the latest evidence on enteric glial reactivity in two prominent inflammatory conditions: acute postoperative inflammation, resulting in postoperative ileus, and chronic inflammation in inflammatory bowel diseases. We define their plasticity during inflammation and the interplay between reactive enteric glia and intestinal macrophages. Finally, we sketch important questions that should be addressed to clarify further the impact of enteric glial reactivity on intestinal inflammation.

Microecological state of the gut after correction of stress-induced dysbiosis by peptide Thr-Lys-Pro-Arg-Pro-Gly-Pro

Stress can disrupt bidirectional communication within the framework of the microbiota-gut-brain axis, including affecting the microbiological landscape and morphofunctional state of the mucous membrane of the colon. In this work we studied the ability of the peptide Thr-Lys-Pro-Arg-Pro-Gly-Pro (tuftsin-pgp) to correct the state of stress-induced dysbiosis in doses of 80, 250 and 750 pg/kg. The increase in the specific content, frequency of occurrence and relative average value of opportunistic bacteria of control stressed animals noted in the study with a decrease in the number and proportion of obligate bacteria indicated active colonization of the mucous membrane of the colon by them. Administration of tuftsin-pgp dose-dependently changed the qualitative and quantitative composition of the studied biotope microbiota. We found out that the most pronounced positive effect on the signs of stress-induced dysbiosis was the administration of the peptide at a dose of 250 pg/kg.

Epigenetics and alternative splicing in cancer: old enemies, new perspectives.

In recent years, significant strides in both conceptual understanding and technological capabilities have bolstered our comprehension of the factors underpinning cancer initiation and progression. While substantial insights have unraveled the molecular mechanisms driving carcinogenesis, there has been an overshadowing of the critical contribution made by epigenetic pathways, which works in concert with genetics. Mounting evidence demonstrates cancer as a complex interplay between genetics and epigenetics. Notably, epigenetic elements play a pivotal role in governing alternative pre-mRNA splicing, a primary contributor to protein diversity. In this review, we have provided detailed insights into the bidirectional communication between epigenetic modifiers and alternative splicing, providing examples of specific genes and isoforms affected. Notably, succinct discussion on targeting epigenetic regulators and the potential of the emerging field of epigenome editing to modulate splicing patterns is also presented. In summary, this review offers valuable insights into the intricate interplay between epigenetics and alternative splicing in cancer, paving the way for novel approaches to understanding and targeting this critical process.

The role of astrocytes from synaptic to non-synaptic plasticity.

Information storage and transfer in the brain require a high computational power. Neuronal network display various local or global mechanisms to allow information storage and transfer in the brain. From synaptic to intrinsic plasticity, the rules of input-output function modulation have been well characterized in neurons. In the past years, astrocytes have been suggested to increase the computational power of the brain and we are only just starting to uncover their role in information processing. Astrocytes maintain a close bidirectional communication with neurons to modify neuronal network excitability, transmission, axonal conduction, and plasticity through various mechanisms including the release of gliotransmitters or local ion homeostasis. Astrocytes have been significantly studied in the context of long-term or short-term synaptic plasticity, but this is not the only mechanism involved in memory formation. Plasticity of intrinsic neuronal excitability also participates in memory storage through regulation of voltage-gated ion channels or axonal morphological changes. Yet, the contribution of astrocytes to these other forms of non-synaptic plasticity remains to be investigated. In this review, we summarized the recent advances on the role of astrocytes in different forms of plasticity and discuss new directions and ideas to be explored regarding astrocytes-neuronal communication and regulation of plasticity.

Gut-Brain Axis and Psychopathology: Exploring the Impact of Diet with a Focus on the Low-FODMAP Approach.

The gut-brain axis (GBA) is a bidirectional communication network connecting the central nervous system with the gastrointestinal (GI) tract, influencing both mental and physical health. Recent research has underscored the significant role of diet in modulating this axis, with attention to how specific dietary patterns can impact anxiety and depression, particularly when linked to disorders of gut-brain interaction (DGBIs), like intestinal bowel syndrome (IBS). This narrative review examines the effects of specific diet regimens on the GBA and its potential role in managing psychopathology, focusing on anxiety and depression, IBS, and the low-FODMAP diet. We conducted a search on PubMed and MEDLINE by combining the following key terms: "Gut-Brain Axis", "Irritable Bowel Syndrome", "Low FODMAP diet", "Mediterranean Diet", "Psychopathology", "Anxiety and Depression", and "Gut Microbiota". We applied the following filters: "Clinical Trials", "Randomized Controlled Trials", "Reviews", "Meta-Analyses", and "Systematic Reviews". In total, 59 papers were included. Low-FODMAP diet, originally developed to alleviate GI symptoms in IBS, may also positively influence mental health by modulating the GBA and improving the gut microbiota (GM) composition. New insights suggest that combining the low-FODMAP diet with the Mediterranean diet could offer a synergistic effect, enhancing both GI and psychological therapeutic outcomes. Understanding the complex interactions between diet, the GM, and mental health opens new avenues for holistic approaches to managing psychopathology, particularly when linked to GI symptoms.

From microbes to mind: germ-free models in neuropsychiatric research.

The gut-microbiota-brain axis refers to the bidirectional communication system between the gut, its microbial community, and the brain. This interaction involves a complex interplay of neural pathways, chemical transmitters, and immunological mechanisms. Germ-free animal models have been extensively employed to investigate gut-microbiota-brain interactions, significantly contributing to our current understanding of the role of intestinal microbes in brain function. However, despite the many benefits, this absence of microbiota is not futile. Germ-free animals present physiological and neurodevelopmental alterations that can persist even after reconstitution with normal microbiota. Therefore, the main goal of this minireview is to discuss how some of the inherent limitations of this model can interfere with the conclusion obtained when using these animals to study the complex nature of neuropsychiatric disorders. Furthermore, we examine the inclusion and use of antibiotic-based treatments as an alternative in the research of gut-brain interactions.