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Results for “Gut-brain-axis”

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PubMed2025

Possible linking and treatment between Parkinson's disease and inflammatory bowel disease: a study of Mendelian randomization based on gut-brain axis.

BACKGROUND: Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel disease (IBD) are closely associated and becoming global health burdens. However, the causal relationships and common pathogeneses between them are uncertain. Furthermore, they are uncurable. Thus, we aimed to identify the causal relationships and novel therapeutic targets shared between them based on their common pathophysiological mechanisms in gut-brain-axis (GBA). METHODS: A meta-analysis on bidirectional Mendelian randomization (MR) utilizing various datasets was performed to estimate their causal relationship. Then, pleiotropic analysis under the composite null hypothesis (PLACO) with functional mapping combined with annotation of genetic associations (FUMA) analysis were conducted to identify pleiotropic genes. Next, blood, brain and intestine expression quantitative trait locus (eQTL) were taken to perform drug-target MR finding common causal genes in two diseases. Colocalization analysis ensured the eQTLs of corresponding gene colocalized with disease. Enrichment analysis and protein‒protein interaction (PPI) network were done to explore common pathogenesis pathways. Genes passed all analysis were regarded as drug targets. RESULTS: Our MR meta-analysis revealed the bidirectional causal relationship between diseases, with combined ORs for PD on IBD, CD, UC (1.050 [95% CI 1.014-1.086], 1.044 [95% CI 0.995-1.095], 1.063 [95% CI 1.016-1.120]); for IBD, CD, UC on PD (1.003 [95% CI 0.973-1.034], 1.035 [95% CI 1.004-1.067], 1.008 [95% CI 0.977-1.040]). Overall, 277, 216 and 201 genes were identified as pleiotropic genes between PD and IBD, CD, UC. Total of 733 genes were classified as tier 3 (found in only one tissue) druggable targets, 57 as tier 2 (found in two tissues, 51 protein-coding genes) and 9 as tier 3 (found in three tissues). Among 60 protein-coding druggable targets over tier 2, 18 overlapped with pleiotropic genes and enriched in mitochondria, antigen presentation, processing and immune cell regulation pathways. Three druggable genes (LRRK2, RAB29 and HLA-DQA2) passed colocalization analysis. LRRK2 and RAB29 were reported to be pleiotropic genes, and RAB29 and HLA-DQA2 were reported for the first time as potential drug targets. CONCLUSIONS: This study established a reliable causal relationship, possible shared drug targets and common pathogenesis pathways of two diseases, which had important implications for intervention and treatment of two diseases simultaneously.

Humans↗

PubMed2025

Impact of the maternal microbiome on neonatal immune development.

Historically, multigenerational health and disease transmission have primarily focused on genetic inheritance. However, the discovery that beneficial microorganisms known as commensal microbiota outnumber human genes tenfold has reshaped this perspective, highlighting their critical role in maintaining homeostasis and protecting against pathogens. Unlike the human genome, commensal microbiota is not genetically inherited but is acquired anew with each generation. with initial gut colonization playing a pivotal role in shaping an infant's immune system, neurodevelopment, and long-term health, all heavily influenced by maternal factors. In this review, we examine emerging research on maternal microbial influences on the fetus beginning in utero. We provide an updated overview of the current insights into the impact of the vaginal microbiome during parturition on offspring immunity and discuss the potential long-term health implications for infants born via cesarean section. We explore the advantages and limitations of techniques designed to mitigate these effects, such as vaginal seeding and emphasize that the development of the neonatal immune system is a dynamic process influenced by maternal factors beyond birth, including the transfer of microbiota through breast milk and skin contact. Finally, we present gaps in current research and propose future research directions to deepen our understanding of the impacts of the maternal microbiome on her child. Together, these insights demonstrate how maternal influence on offspring health and immunity extends beyond genetic factors, encompassing the transmission of microbiota, which, in turn, has profound long-term implications for health and disease resilience, offering a novel perspective on intergenerational health dynamics.

Humans↗

PubMed2025

Nutritional modulation of host physiology, behavior, and gut microbiome in the captive rodent Octodon degus.

Diet is a key determinant of health by affecting nutrient metabolism, energy balance, body weight regulation, and mental health. The gut-brain axis is a critical pathway through which dietary factors influence cognitive function and behavior via microbial metabolites. While this relationship has been extensively studied in traditional laboratory models, diet-microbiome-cognition interactions remain largely unexplored in Octodon degus, an emerging model for aging, neurodegeneration, and cognitive research. Here, we compared two widely used rodent diets-LabDiet and Champion-to evaluate their effects on digestive efficiency, behavior, and gut microbiome composition. We also examined the relationships between these variables using piecewise structural equation modeling (pSEM). Our results indicated that LabDiet-fed degus exhibited enhanced nutrient absorption, higher fecal acetic acid levels, and a higher abundance of Actinobacteria (particularly Bifidobacterium), likely driven by its vitamin C supplementation. These animals also showed improved working memory and social motivation, but they displayed increased anxiety-like behavior. In contrast, Champion-fed degus, which consumed a more fiber-diverse, plant-based diet, showed lower anxiety traits and significantly greater gut microbial richness, with higher abundance of Bacteroidota and Tenericutes. Innate behaviors, such as burrowing and nesting, remained unaffected by the diet. SEM analysis revealed that diet explained most of the variance in microbial activity and identified a positive association between acetic acid levels and cognitive performance. This emphasizes a strong relationship among diet, microbiome, and brain function. Overall, our results suggest that dietary composition is a key factor influencing experimental outcomes in degus, with important implications for physiology, cognition, and microbial ecology. Standardizing dietary inputs is essential to ensure reproducibility in behavioral and biomedical studies using this model. Additionally, our results reinforce the microbiome's role as a mediator of diet-driven brain function via SCFAs, underscoring degus as a powerful system for investigating diet-microbiome-neurobehavioral interactions relevant to aging and mental health.

Animals↗