Search Results (346)

Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal tract that arises from a complex interplay of genetic susceptibility, immune dysregulation, environmental exposures, and altered host–microbiome interactions. Increasing evidence identifies the gut microbiota as a central component of IBD pathogenesis. In healthy individuals, the intestinal microbiota supports epithelial integrity, metabolic homeostasis, immune education, colonization resistance, and bidirectional gut–brain communication. In IBD, this ecosystem is disrupted by reduced microbial diversity, expansion of pathobionts, and broader functional alterations affecting community stability and metabolic output. Importantly, these changes are increasingly viewed not merely as consequences of inflammation, but as active contributors to disease development and persistence. Dysbiosis may also influence neuroimmune signaling through the gut–brain axis, linking microbial metabolites, intestinal barrier dysfunction, enteric nervous system activity, and psychological comorbidities frequently observed in patients with IBD. This review provides a comprehensive overview of the role of the gut microbiota in IBD, beginning with its physiological functions in intestinal homeostasis and the evidence linking dysbiosis to disease pathogenesis, followed by a critical evaluation of current microbiome-based therapeutic strategies, their translational challenges, and prospects for personalized microbiota-directed interventions. Approaches such as fecal microbiota transplantation (FMT), probiotics, live biotherapeutic products, and genetically engineered bacteria aim to restore microbial balance and modulate intestinal inflammation. Among these, FMT has provided the strongest proof-of-concept for microbiome restoration, whereas probiotic efficacy remains variable and strain-dependent. Emerging defined microbial consortia and engineered bacterial platforms offer improved standardization and mechanistic precision, but their clinical application remains limited by challenges related to engraftment, durability of response, safety, and treatment optimization. Collectively, current evidence supports gut microbiota as both a key determinant of IBD pathogenesis and a promising therapeutic target, underscoring the need for more precise and personalized microbiota-directed approaches in IBD management. Full article

Epilepsy is increasingly recognized as a systemic disorder involving complex interactions between the brain and peripheral systems. Among these, the gut microbiota has emerged as a key regulator of host metabolism and immune homeostasis through the production of bioactive metabolites that mediate the communication between gut and brain. In recent years, growing evidence has linked gut dysbiosis to epilepsy, particularly in drug-resistant forms, and interventional studies targeting the gut microbiota in animal models suggest that microbiota-driven metabolic alterations may contribute to seizure generation and recurrence, as well as the associated neuropathology and cognitive deficits. In this review, we summarize current knowledge on the role of the gut microbiota–metabolome axis in acquired epilepsy, with a particular focus on short-chain fatty acids (SCFAs) and tryptophan-derived pathways. SCFAs represent major microbial products involved in energy metabolism, inflammation, blood–brain barrier integrity, neurotransmission and epigenetic mechanisms. In parallel, microbiota-dependent tryptophan metabolism represents a central hub linking intestinal microbial activity to brain function through serotonin, kynurenine, and indole pathways. Dysregulation of these pathways may influence neuronal excitability and contribute to seizures. Converging evidence supports the concept that epilepsy is associated with a coordinated alteration of gut microbial composition and host–microbiota metabolic interactions. However, further research is needed to elucidate the mutual communication between the gut and its microbiota and the metabolic flux, and their influence on brain function in neurological conditions. A better understanding of the underlying pathways and mechanisms may highlight novel therapeutic strategies and discover novel biomarkers of disease trajectory. Full article

Background/Objectives: Gut dysbiosis in children with autism spectrum disorder (ASD) has been associated with alterations in microbial ecology and metabolic function that may contribute to gastrointestinal dysfunction and the severity of clinical manifestations. Synbiotic and probiotic supplementation has emerged as a promising microbiome-targeted strategy for ASD; however, its effects on gut microbiome composition, functional potential, and clinical outcomes remain incompletely understood. We conducted a longitudinal study of Mexican children diagnosed with ASD to analyze changes in the composition, diversity, and functional potential of the gut microbiome during six months of multi-strain synbiotic supplementation. Methods: Stool samples were collected from 25 children with ASD at baseline and after 3 and 6 months of multi-strain synbiotic supplementation. Gut microbiome composition and diversity were analyzed by 16S rRNA gene sequencing, whereas whole metagenome sequencing (WMS) was performed in a subset of samples to evaluate the functional potential of the fecal microbiome. Gastrointestinal symptoms were assessed using the Rome IV criteria, and ASD severity was evaluated with the Childhood Autism Rating Scale (CARS). Results: Twenty-five children with ASD completed the 6 months of synbiotic supplementation. Overall, ASD severity decreased, reflected by a reduction in total CARS score, and improvements in several CARS domains. Gastrointestinal symptoms also decreased significantly. Longitudinal microbiome profiling revealed significant taxonomic and diversity changes over the supplementation period, while WMS identified changes in microbial metabolic potential, including enrichment of tryptophan biosynthesis pathways and reduced L-rhamnose degradation. Conclusions: This exploratory research provides proof-of-concept evidence supporting multi-strain synbiotic supplementation in children with ASD. Larger controlled studies are needed to confirm these findings and clarify their relevance to microbiota–gut–brain axis interactions. The observed concordance between clinical improvements and microbiome remodeling supports further investigation of microbiome-targeted interventions according to ASD severity and duration of supplementation. Full article

Metabolic syndrome (MetS) is a multifactorial disorder characterized by central obesity, insulin resistance, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Recent evidence highlights the important role of the gut–brain axis in the pathogenesis of MetS through complex interactions between the gut microbiota, immune system, endocrine signaling, and host genetics. This narrative review provides an integrative overview of the mechanisms linking dysbiosis to metabolic dysfunction, with particular emphasis on gut microbiota alterations, intestinal permeability, chronic low-grade inflammation, and microbial metabolites such as short-chain fatty acids and lipopolysaccharides. The review also discusses the neural, endocrine, and immune pathways involved in gut–brain communication, including the role of gut-derived neurotransmitters in metabolic regulation. In addition, the contribution of host genetic susceptibility and epigenetic regulation is explored, highlighting how gene–microbiome interactions influence individual metabolic responses and disease risk. Recent advances in multi-omics technologies and precision medicine suggest that personalized approaches targeting both microbial and genetic factors may improve prevention and treatment strategies for MetS. Furthermore, microbiota-targeted interventions, including dietary modifications, probiotics, prebiotics, and fecal microbiota transplantation, are discussed as emerging therapeutic perspectives. Overall, this review emphasizes the importance of considering MetS as a systemic disorder driven by interconnected biological networks involving microbiota, metabolism, immunity, and genetics. Full article

Background: Irritable bowel syndrome (IBS) is a chronic disorder of brain–gut interaction closely linked to psychological stress and highly prevalent among university student populations, yet data from Bahrain remain scarce. This study estimated the frequency of self-reported IBS-like symptoms among university students in Bahrain and examined their associations with sex, age, qualification level, body mass index (BMI), psychological stress, and lifestyle behaviors. Methods: A cross-sectional, online questionnaire-based survey was conducted among 310 students at the University of Bahrain in October 2021. A self-administered 16-item instrument, based on the Rome III symptom domains and used as a symptom-screening rather than a diagnostic tool (face validity only; no formal psychometric validation was performed), assessed sociodemographic characteristics, self-reported IBS-like symptoms, stress and anxiety, and lifestyle behaviors. Data were analyzed using chi-square tests and one-way ANOVA; effect sizes were quantified using Cramér’s V (chi-square) and partial eta-squared (η², ANOVA); the significance threshold was α = 0.05 (two-tailed). Results: Self-reported IBS-like symptoms were common: 52.9% (95% CI 47.3–58.4) reported recurrent abdominal pain, 58.1% (95% CI 52.5–63.4) abdominal bloating, and 80.3% (95% CI 75.5–84.4) reported interference with academic activities. Most participants perceived their mental state (84.8%) and examinations (73.2%) to worsen symptoms, yet only 48.7% correctly identified IBS. Exploratory subgroup analyses suggested differences by qualification level, with diploma-level students reporting higher rates of abdominal pain (p < 0.001; Cramér’s V = 0.22), bloating (p < 0.05; Cramér’s V = 0.13), and perceived psychological impact on symptom severity (p < 0.001; Cramér’s V = 0.19) compared with bachelor- and master-level counterparts. The substantial female over-representation (79%) precluded formal sex-based inference; all findings should be interpreted in this context. Conclusions: Self-reported IBS-like symptoms were commonly endorsed, and participants frequently perceived psychological stress to worsen symptoms. Diploma-level students may represent a previously unrecognized potentially at-risk subgroup warranting further investigation and, if confirmed, targeted stress-focused health-promotion strategies, particularly through brief psychoeducation modules integrated within diploma-program curricula, and dedicated prospective research. Future studies should incorporate validated Rome IV diagnostic criteria, multivariable regression modeling, and biomarker assessment to elucidate underlying brain–gut mechanisms. Full article

Seasonal affective disorder (SAD) is a recurrent mood disorder associated with reduced photoperiod exposure and circadian disruption during autumn and winter. Emerging evidence links SAD to alterations in serotonergic signaling, neuroimmune activity, metabolism, and the microbiota–gut–brain axis; however, the causal relationships among these systems remain incompletely understood. A structured search of PubMed, Web of Science, and Scopus identified relevant publications from 2000 to 2025, with clinical and preclinical evidence evaluated separately. Proposed links between circadian misalignment, inflammatory signaling, and tryptophan metabolism toward the kynurenine pathway are based largely on associative and preclinical findings rather than confirmed mechanisms in SAD. The microbiota–gut–brain axis in SAD is likely bidirectional, as seasonal changes in feeding behavior, physical activity, and circadian phase may themselves influence gut microbial composition and function. Accordingly, microbiome alterations in affective disorders may reflect both potential upstream modulators and downstream consequences of disease-related behavior. Psychobiotics have been proposed as modulators of gut–brain communication in affective disorders. Among candidate strains, Lacticaseibacillus rhamnosus GG (formerly Lactobacillus rhamnosus GG; LGG) has shown effects on intestinal barrier function, immune signaling, and host tryptophan metabolism in preclinical studies. However, evidence derives largely from animal or non-seasonal depression models, and direct evidence in SAD is lacking. Thus, LGG should be considered a mechanistically plausible candidate for future investigation rather than an established therapy. This review synthesizes evidence on circadian regulation, serotonergic and tryptophan metabolism, and microbiota–gut–brain interactions in SAD, and highlights mechanistic gaps for future studies. Full article

Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and a leading cause of dementia worldwide, yet effective disease-modifying therapies remain elusive. Rodent models have been indispensable for elucidating key pathological mechanisms, including amyloid-beta (Aβ) deposition, tau pathology, neuroinflammation, and synaptic dysfunction. However, despite decades of preclinical success, the translation of therapeutic findings from rodent studies to clinical efficacy in humans has been largely unsuccessful, highlighting critical limitations in current modelling approaches. This narrative review provides a comprehensive and critical evaluation of rodent models of AD, encompassing transgenic, chemically induced, metabolic, inflammatory, and lesion-based paradigms. Rather than presenting these models in isolation, we propose a systems-level framework that categorizes them based on their ability to recapitulate distinct domains of AD pathology, including genetic, environmental, and systemic contributors. By synthesising existing research, highlighting critical gaps, and proposing a tiered minimum-criteria framework for the development of next-generation models, we offer a definitive operational roadmap instead of merely a list of deficiencies. We highlight that most existing models predominantly reflect familial and reductionist aspects of the disease, while failing to capture the complexity of sporadic AD, aging processes, vascular dysfunction, and whole-body interactions. Importantly, we emphasize emerging dimensions that are underrepresented in current rodent models, including glymphatic dysfunction, cerebral small vessel disease, and the microbiota–gut–brain axis, all of which play crucial roles in AD pathogenesis. We further discuss how integrating these factors into next-generation models may improve translational relevance and therapeutic predictability. By synthesizing current evidence and identifying key gaps, we provide a strategic roadmap for the development of more physiologically relevant and translationally robust rodent models. Advancing toward integrative, systems-based approaches will be essential for bridging the persistent gap between preclinical discoveries and clinical success in AD. Full article

Growing evidence indicates a bidirectional relationship between the gut microbiota and sleep disturbances in children, with the microbiota–gut–brain axis (MGBA) mediating this interaction. Sleep, circadian rhythms, and the gut microbiota form an interdependent and developmentally dynamic network that plays a crucial role in neurodevelopment during infancy and childhood. Although the mechanisms underlying this complex interaction have not yet been fully elucidated, emerging evidence suggests that multiple dimensions of sleep—including duration, quality, timing, and regularity—are closely associated with gut microbial composition and function. These findings support the rationale for nutritional and microbiota-targeted interventions during critical developmental windows. However, most mechanistic and taxonomic evidence derives from adult or mixed-age cohorts, while methodological heterogeneity, geographic bias, and the predominance of cross-sectional studies limit causal inference. This review provides an overview of the recent literature investigating the role of the gut microbiota in sleep and sleep disorders in children and summarizes potential microbiota-based therapeutic strategies. Full article

Obesity is a major global health problem and is closely associated with a broad range of metabolic disorders, including metabolic syndrome (MetS), dyslipidemia, hypertension, atherosclerosis, type 2 diabetes mellitus, and cardiovascular disease. The gut microbiota plays a central role in maintaining intestinal epithelial integrity, regulating glucose and lipid metabolism, and modulating immune function. Through the gut–brain axis, it also contributes to appetite regulation and energy homeostasis by influencing the release of anorexigenic hormones. Dysbiosis, including alterations in the relative abundance of major bacterial phyla such as Firmicutes and Bacteroidetes, has been associated with increased intestinal permeability, metabolic endotoxemia, and chronic low-grade inflammation, all of which may contribute to the development of obesity and insulin resistance. Diets rich in plant-derived fiber can beneficially shape gut microbiota composition. Bacterial fermentation of dietary fiber produces short-chain fatty acids (SCFAs), including butyrate, acetate, and propionate, which contribute to intestinal barrier integrity, inflammatory regulation, immune regulation, and metabolic homeostasis. Overall, the interaction between gut microbiota, diet, and host metabolic pathways represents a promising field for therapeutic and nutritional interventions aimed at preventing and managing MetS and metabolic diseases. Full article

Background/Objectives: Cholecystectomy, the surgical removal of the gallbladder, is one of the most commonly performed abdominal surgical procedures worldwide. Emerging evidence suggests that cholecystectomy may contribute to the development of irritable bowel syndrome (IBS). However, the association remains incompletely understood. This systematic review and meta-analysis aimed to evaluate the relationship between cholecystectomy and IBS. Methods: A systematic search of PubMed, Embase, Scopus, and Web of Science was conducted from database inception to March 2026. Meta-analyses were performed to pool odds ratios (ORs) and prevalence estimates. Heterogeneity, publication bias, and sensitivity analyses were assessed. Results: Seventeen studies involving 3,511,681 participants were included in the systematic review. Eight studies were eligible for the meta-analysis of the association between cholecystectomy and IBS, while twelve studies contributed to the prevalence analysis. No statistically significant difference in the odds of IBS was observed between patients who underwent cholecystectomy and controls (OR = 2.46, 95% CI: 0.97–6.22; p = 0.056; I² = 91.7%). The pooled prevalence of IBS in post-cholecystectomy patients was 21.0% (95% CI: 9.0–42.0), with high heterogeneity (I² ≈ 99%). Sensitivity analyses did not alter the direction of the pooled estimates following sequential omission of individual studies, and no significant publication bias was detected. Conclusions: No statistically significant difference in the pooled odds of IBS was observed between groups, while the pooled prevalence among cholecystectomy patients was approximately 21%, although heterogeneity was substantial. Further research is needed on heterogeneity. Full article

Background/Objectives: Pediatric acute-onset neuropsychiatric syndrome (PANS) describes the rapid onset of obsessive–compulsive symptoms or severe food restriction, accompanied by neuropsychiatric or somatic features that are not better explained by another disorder. PANDAS (Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infections) is a related, more narrowly defined construct in which symptoms are temporally associated with group A Streptococcus infection. This review examines clinical symptoms, infectious associations, proposed immune mechanisms, biomarker limitations, and treatment strategies for infection-associated PANS/PANDAS. Methods: A structured narrative search of PubMed/MEDLINE, Embase, the Cochrane Library, Google Scholar/publisher-indexed literature, ClinicalTrials.gov, and reference lists was performed up to 16 June 2026. Original cohorts, case series, systematic reviews, narrative reviews, consensus guidance, mechanistic studies, and registered prospective studies were prioritized. The review was not designed as a PRISMA-ScR scoping review; however, the methods were expanded to improve transparency and align with SANRA principles. Results: Group A Streptococcus remains the best characterized infectious association, although prospective studies have not uniformly demonstrated a consistent temporal relationship between streptococcal infection and neuropsychiatric exacerbations. Parent-reported surveys and case-based literature also describe temporal associations with Mycoplasma pneumoniae, influenza-like illnesses, upper respiratory infections, Borrelia burgdorferi, Epstein–Barr virus, and SARS-CoV-2. Proposed mechanisms include molecular mimicry, anti-D1R and anti-D2R antibodies, other antineuronal antibodies, calcium/calmodulin-dependent protein kinase II signaling, blood–brain barrier vulnerability, cytokine and Th17 effects, neuroinflammatory amplification, basal ganglia/CSTC circuit dysfunction, and gut–oral–brain immune interactions. None currently provides a definitive diagnostic biomarker. Conclusions: Infection-associated PANS is best approached as a clinically defined, heterogeneous neuroimmune presentation that requires rigorous differential diagnosis, multidisciplinary care, cautious treatment escalation, prospective biomarker validation, and large, multicenter treatment trials. Full article

Background/Objectives: Irritable bowel syndrome (IBS) is among the most prevalent disorders of gut–brain interaction, yet its implications for spine surgery remain poorly characterized. This narrative review examines how IBS influences symptom presentation and postoperative outcomes in spine surgery patients. Methods: We synthesized the neurobiologic, epidemiologic, and perioperative literature linking IBS with musculoskeletal pain, spine-related symptomatology, and surgical outcomes, drawing on spine-specific data where available and on related surgical and chronic-pain populations where it was not. Results: IBS is characterized by central sensitization, impaired descending inhibition, increased temporal summation, autonomic dysregulation, and a high prevalence of psychiatric comorbidity, which manifest as widespread hyperalgesia and symptom amplification that overlap with pain mechanisms common in spine surgery patients. Epidemiologic studies indicate that patients with IBS undergo musculoskeletal and spinal procedures at disproportionately high rates, reflecting both symptom burden and diagnostic uncertainty from viscerosomatic overlap. These same factors have been associated with greater postoperative pain, elevated opioid requirements, slower functional recovery, and reduced satisfaction after spine surgery, although direct IBS-specific spine data remain limited. IBS may also confound preoperative assessment by mimicking radicular, discogenic, or sacroiliac pain. Conclusions: IBS represents an under-recognized potential modifier of symptom localization, perioperative pain trajectories, and functional recovery in spine surgery. Greater awareness of IBS-related nociplastic and psychosocial mechanisms may improve preoperative evaluation, risk stratification, perioperative management, and the design of future outcome studies. Full article

Introduction: Functional gastrointestinal disorders (FGIDs), conceptualized as disorders of gut–brain interaction, are among the most common chronic or recurrent conditions in childhood, affecting approximately 20–30% of children worldwide across community and clinical settings. FGIDs are associated with substantial impairments in quality of life, frequent school absences, and high levels of psychological comorbidity, contributing to a considerable burden for families and healthcare systems. Despite their high prevalence, the pathophysiology remains incompletely understood, with evidence pointing to a multifactorial interplay of biological, psychological, and environmental factors. Given their frequency across healthcare settings and their significant psychosocial and economic impact, a better characterization of FGIDs in real-world pediatric populations is needed. This retrospective chart review aimed to examine patterns of FGIDs and their associations with gender, temporal factors, geographic setting, and hospitalization burden in a Swiss pediatric cohort within a biopsychosocial framework. Methods: This retrospective chart review study included 1445 patients aged 0–18 years. Patients were selected based on having received an ICD-10 diagnosis attributed to FGID. The frequency and distribution of the aforementioned factors were determined, as well as their associations with each other. Results: A male predominance of FGIDs in newborns (p < 0.001), a female predominance in adolescents (p < 0.001), and sex-based differences in subtype distribution (p < 0.001) was found in this cohort of patients. A higher proportion of FGID cases were found among children in urban areas than in rural and suburban areas. Infants were hospitalized for significantly longer periods on average than older children and males were hospitalized for longer periods on average than females. Discussion and Conclusions: These findings highlight the importance of early, integrated, interdisciplinary care pathways. Given the growing mental health issues affecting adolescent girls and the well-documented bidirectional relationship between emotional stress and FGID symptoms, it is suggested that early psychological screening and family-based interventions could reduce the chronicity of symptoms, prevent unnecessary hospitalizations and improve long-term health outcomes. Full article

Objective: Disorders of gut–brain interaction (DGBIs) are characterized by functional impairments without identifiable organic causes, with their prevalence increasing with age. Emerging evidence suggests that selective serotonin reuptake inhibitors (SSRIs), such as escitalopram oxalate, may influence DGBIs through the brain–gut axis, though the precise mechanisms driving their therapeutic effects remain unclear. This study investigated the impact of escitalopram oxalate on elderly patients with DGBIs in an outpatient department to elucidate these mechanisms. Methods: This study was an observational cohort study. We recruited elderly patients diagnosed with DGBIs. Patients receiving standard treatment alone were assigned to the control group, while patients receiving standard treatment plus 10 mg of escitalopram oxalate daily were assigned to the exposure group. Emotional and gastrointestinal symptoms were assessed at baseline and after 12 weeks of treatment using validated symptom scales. Additionally, stool samples were collected at both time points and analyzed via 16S amplicon sequencing to evaluate the changes in gut microbiota. Results: A total of 83 elderly patients with DGBIs were included in the study, comprising 40 patients in the control group and 43 in the exposure group. After 12 weeks, the exposure group showed significantly greater reductions in their scores on the Gastrointestinal Symptom Rating Scale (GSRS), Short-Form Leeds Dyspepsia Questionnaire (SF-LDQ), Zung Self-Rating Depression Scale (SDS) and Zung Self-Rating Anxiety Scale (SAS) compared with the control group (e.g., GSRS: 17.00 ± 0.85 vs. 22.58 ± 3.18, p < 0.001; p < 0.01 for all other scale comparisons), with higher effective and recovery rates. Notably, the exposure group showed significant alterations in the abundance of four genus-level taxa (Blautia, Butyricicoccus, Prevotellaceae UCG-003, and Streptococcus) and two species-level taxa (Eubacterium-hallii-group and Parabacteroides-merdae). Conclusions: The escitalopram oxalate treatment was associated with significant improvements in both emotional and gastrointestinal symptoms in elderly patients with DGBIs. These improvements may be linked to alterations in specific gut microbiota taxa, offering a preliminary hypothesis for further investigating the underlying mechanisms of the gut–brain axis. Full article

Background/Objectives: Major depressive disorder (MDD) is increasingly recognized as involving inflammation and the microbiota–gut–brain axis. Few studies have simultaneously assessed systemic inflammatory markers and gut microbiota composition within the same cohort while accounting for metabolic confounders. Moreover, data from Middle Eastern and North African (MENA) populations remain limited, restricting our understanding of how diet may influence neuroimmune–microbiome interactions in depression. This study aimed to investigate associations between MDD, systemic inflammatory markers, and gut microbiota composition in Lebanese adults. To our knowledge, this is the first study of its kind in Lebanon, as well as in the MENA region. Methods: In this cross-sectional case–control study, we examined circulating inflammatory markers and gut microbial profiles in 46 adults with DSM-5-confirmed MDD and 25 healthy controls. Plasma C-reactive protein (CRP) and interleukin-6 (IL-6) were measured, and the gut microbiota composition was characterized using 16S rRNA gene sequencing. Multivariable models were adjusted for age, sex, body mass index (BMI), Mediterranean diet adherence, and fluoxetine exposure. Results: Depression status was not independently associated with CRP or IL-6 after adjustment, whereas BMI emerged as a significant determinant of systemic inflammation. At the genus level, MDD was associated with the enrichment of Dorea, Lachnoclostridium, Collinsella, Bilophila, and Klebsiella and the depletion of Christensenella, Mitsuokella, and Victivallis, independent of inflammatory biomarkers. Alpha diversity did not differ between groups, while beta diversity showed modest metric-dependent differences, primarily driven by presence/absence-based measures. Conclusions: Specific microbial taxa may contribute to gut–brain signaling pathways implicated in MDD and systemic inflammation. Further longitudinal and mechanistic studies are required to clarify causal interactions within inflammation–microbiome networks in MDD. Full article