Gut-brain Research Articles

Hypothalamus-pituitary-adrenal and gut-brain axes in biological interaction pathway of the depression

The hypothalamus-pituitary-adrenal (HPA) and gut-brain axes are vital biological pathways in depression. The HPA axis regulates the body's stress response, and chronic stress can lead to overactivation of the HPA axis, resulting in elevated cortisol levels that contribute to neuronal damage, particularly in regions such as the hippocampus and prefrontal cortex, both of which are involved in mood regulation and mental disorders. In parallel, the gut-brain axis, a bidirectional communication network between the gut microbiota and the central nervous system, influences emotional and cognitive functions. Imbalances in gut microbiota can affect the HPA axis, promoting inflammation and increasing gut permeability. This allows endotoxins to enter the bloodstream, contributing to neuroinflammation and altering neurotransmitter production, including serotonin. Since the majority of serotonin is produced in the gut, disruptions in this pathway may be linked to depressive symptoms. This review explores the interplay between the HPA axis and the gut-brain axis in the context of depression.

Nutritional Psychiatry: The Impact of Diet on Mental Health

Nutritional psychiatry is an emerging discipline exploring the intricate relationship between diet and mental health. This field emphasizes the role of dietary patterns, nutrients, and the gut-brain axis in influencing psychological well-being. Research highlights the benefits of specific nutrients, including omega-3 fatty acids, B vitamins, and magnesium, in alleviating symptoms of mood disorders such as depression and anxiety. The Mediterranean diet, rich in plant-based foods and healthy fats, is associated with improved mental health outcomes and reduced cognitive decline. Furthermore, the gut microbiome plays a pivotal role in the gut-brain axis, influencing mood and behavior through complex biochemical pathways. Clinical applications of nutritional psychiatry advocate personalized interventions, dietary assessments, and collaboration with registered dietitians. Despite significant advancements, broader policy reforms and interdisciplinary approaches are essential to integrate nutritional psychiatry into standard mental health care practices. This review underscores the transformative potential of diet as a therapeutic tool in mental health management and calls for continued research to solidify its role in psychiatric care. Keywords: Nutritional psychiatry, Mental health, Gut-brain axis, Mediterranean diet, Nutritional interventions.

Porphyromonas gingivalis Induces Disturbance of Kynurenine Metabolism Through the Gut-Brain Axis: Implications for Alzheimer's Disease.

Porphyromonas gingivalis is one of the major pathogens of chronic periodontitis. P. gingivalis can cause systemic inflammation, amyloid β protein deposition, and hyperphosphorylation of tau protein, leading to Alzheimer's disease (AD)-like lesions. P. gingivalis oral infection causes gut microbiota alteration, gut barrier dysfunction, and intestinal immune response and inflammation. The microbiota-gut-brain axis has a potential role in the pathogenesis of AD. Whether P. gingivalis affects AD-like lesions via the gut-brain axis needs more study. In this study, orally administered P. gingivalis induced alveolar resorption, intestinal barrier impairment, and AD-like lesions. Oral infection with P. gingivalis induced oral and gut microflora dysbiosis, imbalance of the tryptophan metabolism pathway of gut microbiota, and elevated levels of 3-hydroxykynurenine in the sera and hippocampi. The key metabolite, 3-hydroxykynurenine, suppressed Bcl2 gene expression, leading to neuronal apoptosis and promoting AD-like lesions in vivo and in vitro. These findings suggest that P. gingivalis can induce AD pathogenesis through the gut-brain axis, providing new ideas for the prevention and treatment of AD.

Regulation of Gut Starvation Responses Through Drosophila NP3253 Neurons.

The "gut-brain axis," a bidirectional communication system between the gastrointestinal tract and the central nervous system, plays a crucial role in regulating complex physiological functions in response to nutrients, pathogens, and microbiota. However, the cellular and molecular mechanisms governing this regulation remain poorly understood. Using Drosophila melanogaster as a model organism, we previously identified NP3253 neurons, located in both the brain and gut, as key contributors to gut homeostasis during oral bacterial infection. Here, we found a novel role of NP3253 neurons in regulating starvation resistance. We observed that a subset of NP3253 neurons in the gut were activated during starvation. To investigate downstream effect, we conducted RNA-Seq analysis on the gut of adult flies with genetically silenced NP3253 neurons, comparing gene expression under starved and fed conditions. This analysis identified 26 genes differentially expressed in response to both starvation and NP3253 neuronal activity. Among these, CG12643, encoding an uncharacterized short peptide, was found to be essential for starvation resistance in the gut. Our findings demonstrate that NP3253 neurons modulate the gut gene expression in response to starvation, thereby supporting physiological adaptation to environmental stressors.

Photobiomodulation of gut microbiota with low-level laser therapy: a light for treating neuroinflammation.

The gut microbiota is known to interact with various organs in the body, including the central nervous system, through the gut-brain axis. Intestinal dysbiosis can lead to increased peripheral inflammation and, consequently, affect the brain, resulting in neuroinflammation. Photobiomodulation (PBM) has demonstrated positive regulatory effects on the imbalance of certain body functions, including pain, inflammation, immunity, wound healing, and gut microbiota dysbiosis. Therefore, PBM at the intestinal level could help improve intestinal dysbiosis and reestablish cerebral homeostasis. In this context, this study aimed to conduct a narrative review of the literature on the effects of PBM at the intestinal level on intestinal dysbiosis and neuroinflammation. Overall, the findings highlight that PBM modulates the gut microbiota, suggesting it could serve as a therapy for neurological conditions affecting the gut-brain axis. Future research should focus on further elucidating the molecular mechanisms underlying this therapy.

Alzheimer's disease and gut-brain axis: Drosophila melanogaster as a model

Research indicates that by 2050, more than 150 million people will be living with Alzheimer's disease (AD), a condition associated with neurodegeneration due to the accumulation of amyloid-beta and tau proteins. In addition to genetic background, endocrine disruption, and cellular senescence, management of the gut microbiota has emerged as a key element in the diagnosis, progression, and treatment of AD, as certain bacterial metabolites can travel through the bloodstream and cross the blood-brain barrier. This mini-review explores the relationship between tau protein accumulation and gut dysbiosis in Drosophila melanogaster. This model facilitates the investigation of how gut-derived metabolites contribute to neurocognitive impairment and dementia. Understanding the role of direct and indirect bacterial by-products, such as lactate and acetate, in glial cell activation and tau protein dynamics may provide insights into the mechanisms of AD progression and contribute to more effective treatments. Here we discuss how the simplicity and extensive genetic tools of Drosophila make it a valuable model for studying these interactions and testing potential therapeutics, including probiotics. Integrating Drosophila studies with other established models may reveal conserved pathways and accelerate the translation of findings into clinical applications.

A bibliometric analysis of research on dementia comorbid with depression from 2005 to 2024

IntroductionWith the global rise in life expectancy, the incidence of dementia is increasing, often accompanied by depressive symptoms. Understanding the interplay between dementia and depression is crucial, as depression may not only co-occur with but also potentially exacerbate the progression of dementia. This study employs bibliometric analysis to map the global research landscape, identify prevailing themes, and discern future research directions.MethodsWe analyzed reviews and original research articles on dementia and depression extracted from the Web of Science Core Collection spanning from 2005 to 2024. Utilizing tools such as CiteSpace, VOSviewer, and an R-based bibliometric analysis package, we assessed trends in publication volume, citation frequency, contributing countries, leading institutions, predominant journals, influential authors, and emergent keywords.ResultsA total of 1972 publications were obtained, revealing a consistent increase in both the number of publications and their citation impact over the study period. The United States is the country with the most publications and the most extensive collaborations. The University of Toronto and the Journal of Alzheimer’s Disease were identified as key contributors to this field. This research area is currently focused on cognitive impairments, the role of gut microbiota, and non-drug interventions. Future directions emphasize the importance of early detection and intervention, a deeper understanding of the gut-brain axis, and the integration of technology in treatment strategies. Additionally, there is a growing interest in the physiological and psychological interplays such as oxidative stress and its implications.ConclusionThis study underscores pathogenesis, comorbid conditions, and non-drug interventions as primary research focal points, suggesting these areas as potential pathways for therapeutic innovation. These insights are intended to deepen our understanding, enhance diagnostics, and improve the management of dementia and depression, providing guidance for future research aimed at addressing these escalating global health challenges.

Short-Chain Fatty Acid Aggregates Alpha-Synuclein Accumulation and Neuroinflammation via GPR43-NLRP3 Signaling Pathway in a Model Parkinson's Disease.

Parkinson's disease (PD) is characterized by the aggregation of α-synuclein (α-syn) and the loss of dopaminergic (DA) neurons, with growing evidence suggesting a significant role of gut microbiota and their metabolites in the disease's pathogenesis. This study explores the effects of short-chain fatty acids (SCFAs) on PD progression, focusing on the G protein-coupled receptor 43 (GPR43) and the NLRP3 signaling pathway in both in vitro and in vivo models. Employing the1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model and SH-SY5Y cells with SCFAs-treated, this study investigated the impact of SCFAs on α-syn deposition, DA loss, and neuroinflammation. In vitro, supernatant from STC-1 cells was administered to SH-SY5Y cells, and the effects were assessed following the knockdown of NLRP3 or GPR43. In vivo, mice were treated with NLRP3 or GPR43 inhibitors after feeding with SCFAs, and the motor deficits, α-syn pathology, DA neuronal loss, and inflammatory responses were observed. SCFAs were found to exacerbate motor and gastrointestinal dysfunctions in PD models, intensifying α-syn pathology and neuroinflammation. The activation of the NLRP3 inflammasome through GPR43 emerged as a key pathological mechanism, with inhibition of these molecules mitigating the observed effects. Such interventions reduced α-syn accumulation, DA loss, and inflammatory responses, highlighting the pivotal role of the SCFA/GPR43-NLRP3 pathway in PD. The findings from this study elucidate a critical link between gut-derived metabolic changes and neuroinflammatory processes in PD via the SCFA/GPR43-NLRP3 pathway. Targeting this pathway offers a promising therapeutic strategy and enriches our understanding of the gut-brain axis' role in PD progression.

Serotonin attenuates tumor necrosis factor-induced intestinal inflammation by interacting with human mucosal tissue.

The intestine hosts the largest immune system and peripheral nervous system in the human body. The gut‒brain axis orchestrates communication between the central and enteric nervous systems, playing a pivotal role in regulating overall body function and intestinal homeostasis. Here, using a human three-dimensional in vitro culture model, we investigated the effects of serotonin, a neuromodulator produced in the gut, on immune cell and intestinal tissue interactions. Serotonin attenuated the tumor necrosis factor-induced proinflammatory response, mostly by affecting the expression of chemokines. Serotonin affected the phenotype and distribution of tissue-migrating monocytes, without direct contact with the cells, by remodeling the intestinal tissue. Collectively, our results show that serotonin plays a crucial role in communication among gut-brain axis components and regulates monocyte migration and plasticity, thereby contributing to gut homeostasis and the progression of inflammation. In vivo studies focused on the role of neuromodulators in gut inflammation have shown controversial results, highlighting the importance of human experimental models. Moreover, our results emphasize the importance of human health research in human cell-based models and suggest that the serotonin signaling pathway is a new therapeutic target for inflammatory bowel disease.

The role of Akkermansia muciniphila in maintaining health: a bibliometric study

BackgroundAkkermansia muciniphila, as a probiotic, is negatively linked to IBD, obesity, and T2DM. The aim of this study was to comprehensively assess the research status of Akkermansia muciniphila over the past decade and explore the relationships between this bacterium and various health-related aspects.MethodsTools VOSviewer, Bibliometrix, and CiteSpace were used to analyze various aspects including publication metrics, contributors, institutions, geography, journals, funding, and keywords.ResultsOver the past decade, research on Akkermansia muciniphila has demonstrated a consistent annual growth in the number of publications, with a notable peak in 2021. China led in the number of publications, totaling 151, whereas the United States exhibited a higher centrality value. Among the 820 institutions involved in the research, the University of California (from the United States) and the Chinese Academy of Sciences (from China) occupied central positions. Willem M. De Vos ranked at the top, with 12 publications and 1,108 citations. The journal GUT, which had 5,125 citations and an Impact Factor of 23.0 in 2024, was the most highly cited. The most cited articles deepened the understanding of the bacterium’s impact on human health, spanning from basic research to translational medicine. Thirty-nine high-frequency keywords were grouped into five clusters, illustrating Akkermansia muciniphila’s associations with metabolic diseases, chronic kidney disease, the gut-brain axis, intestinal inflammation, and Bacteroidetes-Firmicutes shifts.ConclusionGiven Akkermansia muciniphila’s anti-inflammatory and gut-barrier-strengthening properties, it holds promise as a therapeutic for obesity, metabolic disorders, and inflammatory conditions. Therefore, future research should explore its potential further by conducting clinical trials, elucidating its mechanisms of action, and investigating its efficacy and safety in diverse patient populations.

Gut Microbiota Influences Developmental Anesthetic Neurotoxicity in Neonatal Rats

BACKGROUND: Anesthetic exposure during childhood is significantly associated with impairment of neurodevelopmental outcomes; however, the causal relationship and detailed mechanism of developmental anesthetic neurotoxicity remain unclear. Gut microbiota produces various metabolites and influences the brain function and development of the host. This relationship is referred to as the gut-brain axis. Gut microbiota may influence developmental anesthetic neurotoxicity caused by sevoflurane exposure. This study investigated the effect of changes in the composition of gut microbiota after fecal microbiota transplantation on spatial learning disability caused by developmental anesthetic neurotoxicity in neonatal rats. METHODS: Neonatal rats were allocated into the Control (n = 10) and Sevo (n = 10) groups in Experiment 1 and the Sevo (n = 20) and Sevo+FMT (n = 20) groups in Experiment 2, according to the randomly allocated mothers’ group. The rats in Sevo and Sevo+FMT groups were exposed to 2.1% sevoflurane for 2 hours on postnatal days 7 to 13. Neonatal rats in the Sevo+FMT group received fecal microbiota transplantation immediately after sevoflurane exposure on postnatal days 7 to 13. The samples for fecal microbiota transplantation were obtained from nonanesthetized healthy adult rats. Behavioral tests, including Open field, Y-maze, Morris water maze, and reversal Morris water maze tests, were performed to evaluate spatial learning ability on postnatal days 26 to 39. RESULTS: Experiment 1 revealed that sevoflurane exposure significantly altered the gut microbiota composition. The relative abundance of Roseburia (effect value: 1.01) and Bacteroides genus (effect value: 1.03) increased significantly after sevoflurane exposure, whereas that of Lactobacillus (effect value: −1.20) decreased significantly. Experiment 2 revealed that fecal microbiota transplantation improved latency to target (mean ± SEM; Sevo group: 9.7 ± 8.2 seconds vs, Sevo+FMT group: 2.7 ± 2.4 seconds, d=1.16, 95% confidence interval: −12.7 to −1.3 seconds, P = .019) and target zone crossing times (Sevo group: 2.4 ± 1.6 vs, Sevo+FMT group: 5.4 ± 1.4, d=1.99, 95% confidence interval: 2.0–5.0, P < .001) in the reversal Morris water maze test. Microbiota analysis revealed that the α-diversity of gut microbiota increased after fecal microbiota transplantation. Similarly, the relative abundance of the Firmicutes phylum (effect value: 1.44), Ruminococcus genus (effect value: 1.69), and butyrate-producing bacteria increased after fecal microbiota transplantation. Furthermore, fecal microbiota transplantation increased the fecal concentration of butyrate and induced histone acetylation and the mRNA expression of brain-derived neurotrophic factor in the hippocampus, thereby suppressing neuroinflammation and neuronal apoptosis. CONCLUSIONS: The alternation of gut microbiota after fecal microbiota transplantation influenced spatial learning ability in neonatal rats with developmental anesthetic neurotoxicity. Modulation of the gut microbiota may be an effective prophylaxis for developmental anesthetic neurotoxicity in children.

Gut-brain axis mediated by intestinal content microbiota was associated with Zhishi Daozhi decoction on constipation

BackgroundConstipation is a common digestive system disorder, which is closely related to the intestinal flora. Zhishi Daozhi decoction (ZDD) is a traditional Chinese medicine prescription used to treat constipation caused by indigestion. This study is to evaluate the efficacy of ZDD in treating constipation and to elucidate the underlying mechanism.MethodsIn this study, Kunming mice were administered a high-protein diet (HFHPD) and loperamide hydrochloride injections to induce constipation. The mice then received varying doses (2.4, 4.7, and 9.4 mg/kg) of ZDD for seven days. Following the sampling process, we measured fecal microbial activity. The levels of 5-hydroxytryptamine (5-HT), vasoactive intestinal peptide (VIP), and aquaporin-3 (AQP3) were quantified using enzyme-linked immunosorbent assay. Changes in the gut microbiota were evaluated through 16S rRNA gene sequencing. Additionally, we investigated the correlation between specific microbiota features and the levels of 5-HT, VIP, and AQP3.ResultsThe fecal surface of the mice in the model group (CMM) was rough and dry. The stool of mice in the low-dose ZDD group (CLD), medium-dose ZDD group (CMD), and high-dose ZDD group (CHD) exhibited a smoother texture, closely resembling that of the normal group (CNM). 5-HT levels in the CMM group were significantly lower than in the CNM, CLD, and CHD. VIP levels in the CMD were lower than in the other four groups, and AQP3 levels in CMM showed a decreasing trend. The fecal microbial activity of the CMM group was significantly higher than that of the other groups. Diversity analysis indicated that CMD and CHD treatments were more effective in restoring the intestinal microbiota structure. Potential pathogenic bacteria, including Clostridium, Aerococcus, Jeotgalicoccus, and Staphylococcus were enriched in CMM. In contrast, beneficial bacteria such as Faecalibacterium, Bacillaceae, and Bacillus were more prevalent in the CLD, CMD, and CHD. Correlation analysis revealed that Streptococcus and Enterococcus were positively correlated with VIP, while Succinivibrio showed a negative correlation with 5-HT.ConclusionsConstipation induced by HFHPD and loperamide hydrochloride disrupts the structure of the intestinal microbiota. ZDD appears to alleviate constipation, potentially through mechanisms linked to the brain-gut axis and its interaction with the intestinal microbiota. Among the treatment groups, the medium dose of ZDD demonstrated the most effective results.

Vaginal Seeding: Is There Any Positive Effect in Canine C-Sections?

This study aimed to scrutinize variations in the intestinal microbiota of neonatal dogs born through natural birth versus elective cesarean section, focusing on evaluating the influence of vaginal seeding on the microbiota of cesarean-born neonates. Samples were collected from cesarean-sectioned females before anesthesia and from naturally birthing females during prodrome signs, along with neonates at eight time points from birth to 15 days of age. In the cesarean section group, seeding was performed in half of the neonates (cesarean section seeding group; seeding consisted of gently rubbing the gauze, obtained from the mother’s vagina, onto the mouths, faces, and bodies of the newborns), while the other half underwent microbiological sample collection without seeding (cesarean section group). Another group (normal birth group) consisted of naturally born neonates. Microbiota analysis included counting for enterobacteria, Staphylococcus spp., and Streptococcus spp. The results suggested that vertical transmission played a crucial role, but the method of birth did not emerge as the primary determinant of observed differences. Under study conditions, vaginal seeding failed to effectively modulate the microbiota of neonates born through elective cesarean section. Further investigations into the gut–brain axis are suggested for understanding factors influencing the initial development of the canine intestinal microbiota in neonates born through different delivery routes.

Electroacupuncture and Tongbian decoction ameliorate CUMS-induced depression and constipation in mice via TPH2/5-HT pathway of the gut-brain axis.

Depression is commonly associated with gastrointestinal (GI) disorders, such as constipation, which can potentially intensify depressive symptoms. The interplay between these conditions is believed to be facilitated by the gut-brain axis, which suggests a complex bidirectional interaction. Current treatments, such as antidepressants and prokinetics, are often associated with side effects and high recurrence rates, highlighting the need for effective treatments targeting both depression and constipation. This study was designed to assess the therapeutic efficacy of electroacupuncture (EA) in conjunction with Tongbian decoction (TB) for the management of both depression and constipation, while also investigating the underlying mechanisms through the lens of the gut-brain axis. Chronic unpredictable mild stress (CUMS) was employed to induce a comorbidity model of depression and constipation in mice, followed by the administration of EA, EA + TB, and fluoxetine (FLX). The findings of the study demonstrated that the antidepressant effects of electroacupuncture (EA) in combination with Tongbian decoction (TB) were more pronounced than those of EA alone. The EA + TB treatment significantly ameliorated depression and anxiety-like behaviors, restored cognitive function, and enhanced gastrointestinal motility in chronic unpredictable mild stress (CUMS) mice. Furthermore, EA + TB reduced intestinal inflammation, restored neuronal morphology, increased the expression of tryptophan hydroxylase 2 (TPH2) in both the prefrontal cortex (PFC) and colon, elevated the serum levels of 5-hydroxytryptophan (5-HTP)-a molecule that acts as a gut-brain connector-and promoted the synthesis and production of serotonin (5-HT) in both the gastrointestinal tract and the brain. Contrastingly, FLX showed limited efficacy in improving constipation. In conclusion, EA + TB regulates the TPH2/5-HT pathway via the gut-brain axis, demonstrating synergistic regulation of the nervous and gastrointestinal systems, with favorable antidepressant and prokinetic effects.

Antibiotics/coccidiostat exposure induces gut-brain axis remodeling for Akt/mTOR activation and BDNF-mediated neuroprotection in APEC-infected turkeys

The poultry industry relies extensively on antibiotics and coccidiostats as essential tools for disease management and productivity enhancement. However, increasing concerns about antimicrobial resistance (AMR) and the toxicological safety of these substances have prompted a deeper examination of their broader impacts on animal and human health. This study investigates the toxicological effects of antibiotics and coccidiostats on the gut-brain axis and microbiota in turkeys, with a particular focus on molecular mechanisms that may influence neurochemical and inflammatory responses. Our findings reveal that enrofloxacin exposure leads to the upregulation of BDNF, suggesting a neuroprotective effect, while monensin treatment significantly increased eEF2 kinase expression, indicative enhanced neuronal activity. In turkeys infected with Avian Pathogenic Escherichia coli (APEC), early administration of doxycycline and monensin significantly upregulated the mTOR/BDNF and Akt/mTOR pathways, along with elevated histamine levels, underscoring their role in inflammatory responses modulation. However, treatments administered at 50 days post-hatch did not significantly alter protein levels, though both enrofloxacin and monensin increased serotonin and dopamine levels, suggesting potential neurotoxicological impacts on mood and cognitive functions. These results highlight the complex interactions between antibiotic use, gut microbiota alterations, and neurochemical pathways, with toxicological implications for environmental pollution and public health. This research provides critical insights into the potential toxic effects of prolonged antibiotic and coccidiostat exposure in poultry production, emphasizing the need for responsible use to mitigate risks to ecosystems and human health.

Role of AIM2 and cGAS-STING signaling in high fat high carbohydrate diet-induced gut dysbiosis associated neurodegeneration.

Gut dysbiosis modulates CNS complications and cognitive decline through the gut-brain axis. The study aims to investigate the molecular mechanisms involved in gut dysbiosis-associated cognitive changes and the potential effects of probiotics in high fat-high carbohydrate diet-induced gut dysbiosis-associated neurodegeneration. We used high fat, high-carbohydrate diet (HFHCD) and high-fat diet (HFD) to induce gut dysbiosis-associated neurodegeneration in C57BL/6 mice. IVIS imaging system and biochemical changes using ELISA measured intestinal inflammation. We used fecal samples for qPCR profiling of intestinal bacteria, and serum was used for inflammatory marker analysis using ELISA. Behavioral studies measured cognitive changes, while histopathology, immunohistochemistry, and western blot analysis of hippocampal samples measured protein changes. The behavioral studies showed a significant decrease in cognitive function associated with gut dysbiosis in HFHCD and HFD animals. Gut dysbiosis was associated with intestinal inflammation and increased intestinal permeability, followed by systemic and neuroinflammatory changes. Molecular signaling studies showed the involvement of AIM2 inflammasome and cGAS-STING signaling pathways in neurodegeneration for HFHCD animals. Administration of probiotics restored the above processes and prevented gut dysbiosis-associated memory decline in mice. The study shows that alteration in microbial composition due to prolonged HFHCD could contribute to intestinal inflammation and increased intestinal permeability, facilitating the translocation of microbial toxins like LPS, leading to systemic inflammation, which eventually leads to neuroinflammation and neurodegeneration.

Synergistic interactions between gut microbiota and short chain fatty acids: Pioneering therapeutic frontiers in chronic disease management.

Microorganisms in the gut play a pivotal role in human health, influencing various pathophysiological processes. Certain microorganisms are particularly essential for maintaining intestinal homeostasis, reducing inflammation, supporting nervous system function, and regulating metabolic processes. Short-chain fatty acids (SCFAs) are a subset of fatty acids produced by the gut microbiota (GM) during the fermentation of indigestible polysaccharides. The interaction between GM and SCFAs is inherently bidirectional: the GM not only shapes SCFAs composition and metabolism but SCFAs also modulate microbiota's diversity, stability, growth, proliferation, and metabolism. Recent research has shown that GM and SCFAs communicate through various pathways, mainly involving mechanisms related to inflammation and immune responses, intestinal barrier function, the gut-brain axis, and metabolic regulation. An imbalance in GM and SCFA homeostasis can lead to the development of several chronic diseases, including inflammatory bowel disease, colorectal cancer, systemic lupus erythematosus, Alzheimer's disease, and type 2 diabetes mellitus. This review explores the synergistic interactions between GM and SCFAs, and how these interactions directly or indirectly influence the onset and progression of various diseases through the regulation of the mechanisms mentioned above.

Chitosan and its derivatives: A novel approach to gut microbiota modulation and immune system enhancement.

Chitosan, a biopolymer derived from the deacetylation of chitin found in crustacean shells and certain fungi, has attracted considerable attention for its promising health benefits, particularly in gut microbiota maintenance and immune system modulation. This review critically examines chitosan's multifaceted role in supporting gut health and enhancing immunity, beginning with a comprehensive overview of its sources, chemical structure, and its dual function as a dietary supplement and biomaterial. Chitosan's prebiotic effects are highlighted, with a focus on its ability to selectively stimulate beneficial gut bacteria, such as Bifidobacteria and Lactobacillus, while enhancing gut barrier integrity and inhibiting the growth of pathogenic microorganisms. The review delves deeply into chitosan's immunomodulatory mechanisms, including its impact on antigen-presenting cells, cytokine profiles, and systemic immune responses. A detailed comparative analysis assesses chitosan's efficacy relative to other prebiotics and immunomodulatory agents, examining challenges related to bioavailability and metabolic activity. Beyond its role in gut health, this review explores chitosan's potential as a dual-action agent that not only supports gut microbiota but also fortifies immune resilience. It introduces emerging research on novel chitosan derivatives, such as chitooligosaccharides, and evaluates their enhanced bioactivity for functional food applications. Special attention is given to sustainability, with an exploration of alternative, plant-based sources of chitosan and their implications for both health and environmental stewardship. Also, the review identifies new research avenues, such as the growing interest in chitosan's role in the gut-brain axis and its potential mental health benefits through microbial interactions. By addressing these innovative areas, the review aims to shift the focus from basic health effects to chitosan's broader impact on public health. The findings encourage further exploration, particularly through human trials, and emphasize chitosan's untapped potential in revolutionizing health and disease management.

Behavioural, cognitive, and neurophysiological effects of a synbiotic supplementation enriched with pigmented corn extract or cornstarch in drug-naïve children with attention-deficit hyperactivity disorder: A randomised, double-blind, comparison-controlled clinical trial.

Considerable interest has been recently given to the potential role of the gut-brain axis (GBA) -a two-way communication network between the gut microbiota and the central nervous system- in the pathogenesis of attention-deficit hyperactivity disorder (ADHD), suggesting the potential usefulness of probiotic and synbiotic supplementations. In light of the limited available evidence, synbiotic efficacy in ADHD children not taking medications should be clarified. This study aimed to investigate the efficacy of a synbiotic dietary supplementation on fatty acids levels as well as on microbiota composition, behaviour, cognition, and brain function in children with ADHD. A total of 41 drug-naïve school-aged children diagnosed with ADHD were enrolled in a 3-month randomised, double-blind, comparison-controlled clinical trial, receiving either a synbiotic mix (COMP group) or the same synbiotic mix enriched with an additional extract from pigmented corn (EXP group). Changes in levels of some specific short-chain and branched-chain fatty acids were considered as primary outcomes. Secondary outcome measures included gut microbiota profiling, Child Behaviour Checklist, Conners Parent Rating Scale-revised, computerised cognitive tasks, and haemodynamic response to a Go-NoGo task measured by fNIRS. No superiority of the EXP synbiotic mix was observed. Analysis of fatty acids did not reveal any significant difference between groups. Children in the COMP group reported a slightly greater improvement than those in the EXP group in focused attention and in the haemodynamic response to a cognitive task. This study shows that pigmented corn extract does not enhance the effects of the synbiotic supplementation in ADHD children in terms of fatty acid production, microbiota composition, clinical, cognitive and neurophysiological measures. However, a synbiotic mix of probiotics plus prebiotic acacia fibre and cornstarch could have some promising effects on ADHD symptoms, which warrants further research. Future studies should also continue to explore the potential of fNIRS for monitoring the effects of interventions that target the GBA. ClinicalTrials.gov: NCT06005506.

Association of Longitudinal Oral Microbiome Activity and Pediatric Concussion Recovery

Mild traumatic brain injury (mTBI) results in a constellation of symptoms commonly referred to as a concussion. It is unclear why certain individuals experience persistent symptoms. Given the growing evidence linking the microbiome with cognition and inflammation, we examined whether longitudinal microbiome patterns were associated with concussion symptoms. A cohort study of 118 children (aged 7–21 years) was conducted. Symptoms were assessed at three timepoints post-injury (4, 11, and 30 days) using the Post-Concussion Symptom Inventory. Saliva microbial activity was measured at each timepoint using RNA sequencing. A linear mixed model assessed the relationship between microbial activity and symptom burden while controlling for age, sex, and days post-mTBI. The participants’ mean age was 16 (±3) years. The symptom burden decreased across all three timepoints (25 ± 22, 13 ± 17, and 5 ± 12). The longitudinal symptom burden was associated with elevated activity of Lactobacillus (F = 5.47; adj. p = 0.020) and Saccharomyces (F = 6.79; adj. p = 0.020) and reduced activity of Micrococcus (F = 7.94, adj. p = 0.015). These results do not establish a causative relationship, or support the use of microbial measures as a concussion test. Further studies are needed to explore the role of the gut–brain axis in mTBI.