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Empirical evidence for gut microbial influence on human brain neurochemistry via the gut-brain axis.
The gut microbiome produces metabolites with potential neuroactive properties, many of which act locally within the gut. While preclinical studies suggest these microbial pathways can influence cognitive and emotional processes, human evidence remains limited. This study investigates associations between gut microbiome-derived neuroactive functional potential and in vivo brain neurotransmitter concentrations in healthy young females. Using proton magnetic resonance spectroscopy (¹H-MRS), we quantified GABA and glutamate levels in the dorsolateral prefrontal cortex (dlPFC), anterior cingulate cortex (ACC), and inferior occipital gyrus (IOG). Parallel metagenomic profiling characterised microbial functional potential for pathways related to the synthesis and degradation of GABA, glutamate, short-chain fatty acids (SCFAs), p-cresol, and inositol. Region-specific associations were observed between these microbial pathways and cortical GABA and glutamate levels, including excitatory/inhibitory (E/I) balance, a key marker of neuroplasticity and mental health. Notably, microbial glutamate degradation and inositol synthesis potential were associated with IOG E/I balance, while additional pathways including GABA metabolism, p-cresol production, and SCFA synthesis showed distinct associations across regions. Exploratory analyses also identified links between microbial functional potential and anxiety, depressive symptoms, and sleep quality. Together, these findings provide new human evidence that variation in microbial functional potential corresponds with regional cortical neurochemistry and psychological wellbeing, highlighting the gut-brain axis as a promising avenue for mechanistically informed microbiome-based- interventions.
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Camel milk-based probiotics: functional properties, gut health benefits, and emerging implications for the gut-brain axis-a comprehensive review.
UNLABELLED: Camel milk is gaining scientific interest for its unique composition, including bioactive proteins, high antimicrobial peptides (lactoferrin, lysozyme), immunomodulatory components, and lower allergenic potential compared to bovine milk, positioning it as a promising matrix for probiotic delivery. Probiotics support gut homeostasis and may influence the gut-brain axis via microbial metabolites (SCFAs, GABA), immune modulation, and neuroactive compound production. This review critically assesses current evidence on camel milk-based probiotics, emphasizing functional properties, effects on gut microbiota, gastrointestinal benefits, and emerging implications for the gut-brain axis (inflammation reduction, metabolic signaling, neurotransmitter pathways). Drawing from in vitro studies, animal models (e.g., colitis, EAE, diabetes), and limited human trials, we evaluate translational relevance. Preliminary findings suggest benefits in gut health, microbiota modulation, and potential neuroprotection, but strain specificity, mechanistic details, and robust clinical efficacy remain limited. Significant knowledge gaps persist regarding optimal strains, dosing, and long-term effects. Rigorous, well-designed preclinical and clinical studies are essential to validate health claims and support development of camel milk-based functional products targeting gut and potential neurological health. GRAPHICAL ABSTRACT: The graphical abstract illustrates camel milk-derived probiotics as modulators of the gut-brain axis through interconnected pathways. Central mechanisms include microbiota modulation, synthesis of neuroactive compounds (SCFAs, GABA, neurotransmitters), immune regulation, and anti-inflammatory effects. Bidirectional communication between gut and brain occurs via neural, endocrine, and metabolic routes, with potential therapeutic applications for mental health disorders including depression, anxiety, and cognitive impairment. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s13197-026-06765-x.
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Altered Gut Microbiota and Plasma Metabolome Profiles Characterize Depression Individuals with Ischemic Stroke: A Comparative Analysis.
PURPOSE: Depression has been recognized as a significant risk factor for ischemic stroke (IS). This study aimed to describe gut microbiota differences between depression people with and without IS, thereby establishing the link between gut microbiota and an elevated risk of IS development in people with depression. PEOPLE AND METHODS: This study included 30 hospitalized patients with comorbid depression and IS, and 30 age-/sex-matched patients with depression alone. We used two approaches: (1) genetic analysis techniques (16S rRNA gene sequencing) to map gut microbial ecosystems, and (2) broad-spectrum chemical (nontargeted metabolomics) analysis to detect blood metabolites. RESULTS: Alpha (α)-diversity and beta (β)-diversity of people with depression, with or without IS, did not show significant differences between the two groups. The IS group showed increased levels of gut bacteria carrying pro-inflammatory molecules, specifically Gram-negative Enterobacteriaceae containing lipopolysaccharide (LPS) components, the Linear discriminant analysis (LDA) value =4.177, P=0.014. Alongside, the IS group reduced populations of beneficial microbes that produce butyric acid important for gut health, such as Acidaminococcaceae (LDA value =4.045, P=0.014), Roseburia (LDA value =3.894, P=0.007), and Fusicatenibacter (LDA value =3.345, P=0.012), compared to the non-IS group. 38 plasma metabolites with significant differences between people with IS and non-IS groups. The abundance of Alloprevotella and Bacteroides massiliensis was correlated with 9 and 4 metabolites, respectively. CONCLUSION: This study highlighted that people with depression and IS exhibited distinct alterations in both their gut microbiome and metabolite profiles, in contrast to people with depression without IS. These findings may guide future interventions targeting gut microbiota to identify IS in depression people.
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The brain-gut axis: communication mechanisms and the role of the microbiome as a neuroprotective factor in the development of neurodegenerative diseases: A literature overview.
The study of the brain-gut axis and its impact on cognitive function and in the development of neurodegenerative diseases is a very timely topic of interest to researchers. This review summarizes information on the basic mechanisms of gut-brain communication. We then discuss the roles of the gut microbiome as a neuroprotective factor in neurodegeneration. The gut microbiota is extremely important in maintaining the body's homeostasis, shaping the human immune system and the proper functioning of the brain. The intestinal microflora affects the processes of neuroplasticity, synaptogenesis, and neuronal regeneration. This review aims to explain changes in the composition of the bacterial population of the intestinal microflora among patients with Alzheimer's disease, Parkinson's disease, and multiple sclerosis. Abnormalities in gut microflora composition are also noted in stress, depression, or autism spectrum development. New observations on psychobiotic supplementation in alleviating the symptoms of neurodegenerative diseases are also presented.
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Characteristics of Gut Microbiota and Plasma Metabolites in Patients with Post-Stroke Depression.
PURPOSE: The changes in gut microbiota and plasma metabolites have been proposed to play a key role in post stroke depression (PSD), but clinical study based on combined omics is still in lack. This study aimed to investigate the characteristics of gut microbiota and plasma metabolites in patients 3 months after the onset of acute ischemic stroke (AIS), compare PSD and non-PSD groups, and explore possible diagnostic biomarkers. PATIENTS AND METHODS: Seventy patients with stroke were included at 3 months after AIS onset. Plasma and fecal samples were collected. Gut microbiome was examined using 16S rRNA sequencing, and plasma metabolites were assessed via targeted liquid chromatography-mass spectrometry. RESULTS: Of the 70 patients with ischemic stroke, 25 (35.71%) were diagnosed with PSD. At the genus level, patients with PSD had increased abundance of Parabacteroides, Pyramidobacter, Anaeroglobus, Haliangium, Staphylococcus, CAG-56, Shuttleworthia, and Epulopiscium, and decreased levels of the Eubacterium eligens group and Prevotella. In patients with PSD, 12 plasma metabolites were altered, with cortisol and pyroglutamic acid levels increased, while 2-phosphoglyceric acid, 3-phosphoglycerate, phosphorylcholine, tryptophan, caffeine, N-methylalanine, ornithine, serotonin, theophylline, and vanillic acid were decreased. Enriched metabolic pathways included glutathione, tryptophan, and caffeine metabolism. Furthermore, significant correlations were observed between gut microbial dysregulation and major plasma metabolite alterations. The areas under the curve values of gut microbiota, plasma metabolites, and the combined dataset for PSD diagnosis were 0.704, 0.875, and 0.940, respectively. CONCLUSION: This study identified the characteristics of gut microbiota and plasma metabolites as well as a panel of combined biomarkers in 3-month PSD, possibly providing a new theoretical framework for diagnosis and treatment.
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COVID-19: A pandemic that threatens physical and mental health by promoting physical inactivity.
Ever since the outbreak of Coronavirus disease 2019 (COVID-19) in late 2019, it has killed millions of people worldwide. Even people not stricken by this disease are not spared from its negative economic, social, and health-related drawbacks. This commentary provides insight into the potential mechanisms involved in the development of depression and emotional negativity escalating during the current pandemic. In particular, preventive measures of COVID-19, such as staying at home, are sedentarism measures that decrease physical activity. Physical inactivity alters gut microbiome structure in a fashion that promotes gut dysbiosis and flaring of systemic inflammation, leading to the buildup of body fat. Obesity, which contributes to a trail of health-depleting disorders, furthers gut microbial disintegration while fat tissue stimulates the release of cytokines, promotes metabolic resistance, and alters signaling involved in the production of antioxidants. As a result, the body gets flooded by toxic molecules such pro-inflammatory mediators, free radicals, and advanced glycation end products. These toxic molecules alter cellular function in all body tissues, including those of the brain. Neuroinflammation is associated with progressive declines in cognitive and motor functions along with dysregulation in emotions. Counteracting the sedentarism enforced by the COVID-19 pandemic through the participation in suitable indoors activities and the intake of healthy food is likely to protect against or revert physiological impairments that may affect people retreating to their homes during the current crisis, eventually restoring physical and mental health.
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Synergistic Neuroimmune Modulation by Cannabidiol and Probiotics for Therapeutic Advancement in CNS Disorders: A Systematic Review.
INTRODUCTION: The gut-brain axis (GBA) is a complex, bidirectional communication network connecting the gastrointestinal tract and central nervous system. Cannabidiol (CBD) and probiotics have shown promising neuroprotective, anti-inflammatory, and immunomodulatory effects. However, the synergistic potential of these agents on the GBA has not been fully explored. METHODS: A systematic review of recent preclinical and clinical studies was conducted using databases such as PubMed, Scopus, Web of Science, Science Direct, and Google Scholar. The review focused on the individual and combined effects of CBD and probiotics on gut microbiota composition, neuroinflammation, neurotransmitter modulation, and immune signalling. Mechanistic insights involving the endocannabinoid system and microbiome-derived metabolites were also analyzed. RESULTS: Evidence suggests that both CBD and probiotics can enhance gut microbial diversity, regulate pro-inflammatory cytokines, and increase neuroactive metabolites like serotonin and short-chain fatty acids. These effects may improve vagus nerve activity and gut-brain communication, indicating therapeutic potential for managing anxiety, depression, and neurodegenerative conditions. However, human studies remain limited in scale and duration. DISCUSSION: The observed benefits of CBD and probiotics suggest a synergistic mechanism through gut-brain axis modulation, addressing both neurological and immunological pathways. While animal studies are promising, translation to clinical practice requires further evidence. CONCLUSION: CBD and probiotics represent a novel combinatorial approach for managing central nervous system disorders through GBA modulation. Future clinical trials should establish optimal dosing, long-term safety, and therapeutic efficacy to validate their use in neuroimmune conditions.
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Evidence for Brain-To-Gut and Gut-To-Brain Pathways in Primary Care Patients With Disorders of Gut-Brain Interaction, Inflammatory Bowel Disease and Gastroesophageal Reflux Disease.
BACKGROUND: Apart from disorders of gut-brain interaction (DGBI), little data exist on the magnitude of the brain-to-gut pathway in other chronic gastrointestinal conditions such as gastroesophageal reflux disease (GERD) or inflammatory bowel disease (IBD) and what factors modify order of diagnosis. We aimed to determine the proportion of patients who received a diagnosis of a DGBI, GERD, or IBD prior to a new psychological diagnosis (gut-to-brain), and vice versa (brain-to-gut), and whether specific factors moderate the order of diagnosis. METHOD: Data was collected from a retrospective study of 1,129,104 patients attending general practices in the United Kingdom. Patients diagnosed with DGBI, GERD, or IBD and a psychological disorder (anxiety and/or depression) were included (excluding those with other organic GI disease). Information on which diagnosis appeared first was recorded. Multiple logistic regression was performed to compare a diagnosis of a DGBI, GERD, or IBD first versus a psychological diagnosis first on sociodemographic factors, medical conditions, and medication usage. KEY RESULTS: Just over half of patients were diagnosed with a psychological condition first versus after for IBS (53.9%) and ulcerative colitis (55.6%). This proportion was higher for FD (61.5%) and GERD (64.2%) but lower for Crohn's disease (45.7%). In a multivariate model, being female (OR = 1.37, 95% CI 1.25, 1.49), prior PPI (OR = 9.17, 95% CI 8.4, 10.0), antibiotic (OR = 2.54, 95% CI 2.29, 2.81) and NSAID use (OR = 1.29, 95% CI 1.18, 1.42), and prior gastroenteritis (OR = 2.19, 95% CI, 1.79, 2.67) were significant predictors for being diagnosed with GERD first. Similar results were found for DGBI. CONCLUSIONS & INFERENCES: Prior medication usage and gastroenteritis may play a role in generating gut-to-brain pathway disturbances.
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Pubertal consumption of R. badensis subspecies acadiensis modulates LPS-induced immune responses and gut microbiome dysbiosis in a sex-specific manner.
Puberty is a critical period of development characterized by significant brain remodeling and increased vulnerability to immune challenges. Exposure to an immune challenge such as LPS during puberty can result in inflammation and gut dysbiosis which may lead to altered brain functioning and psychiatric illnesses later in life. However, treatment with probiotics during puberty has been found to mitigate LPS-induced peripheral and central inflammation, prevent LPS-induced changes to the gut microbiota and protect against enduring behavioural disorders in a sex-specific manner. Recent findings from our laboratory revealed that pubertal R. badensis subspecies acadiensis (R. badensis subsp. acadiensis) treatment prevents LPS-induced depression-like behavior and alterations in 5HT1A receptor expression in a sex-specific manner. However, the underlying mechanism remains unclear. Thus, the aim of this study was to gain mechanistic insights and to investigate the ability of R. badensis subsp. acadiensis consumption during puberty to mitigate the effects of LPS treatment on the immune system and the gut microbiome. Our results revealed that pubertal treatment with R. badensis subsp. acadiensis reduced sickness behaviors in females more than males in a time-specific manner. It also mitigated LPS-induced increases in pro-inflammatory cytokines in the blood and in TNFα mRNA expression in the prefrontal cortex and the hippocampus of female mice. There were sex-dependent differences in microbiome composition that persisted after LPS injection or R. badensis subsp. acadiensis consumption. R. badensis subsp. acadiensis had greater impact on the microbiota of male mice but female microbiota's were more responsive to LPS treatment. This suggested that female mice microbiota's may be more prone to modulation by this probiotic. These findings emphasize the sex-specific effects of probiotic use during puberty on the structure of the gut microbiome and the immune system and highlight the critical role of gut colonization with probiotics during adolescence on immunomodulation and prevention of the enduring effects of infections.
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Role of gut microbiome in regulating the effectiveness of metformin in reducing colorectal cancer in type 2 diabetes.
The prevalence of colorectal cancer (CRC) and type 2 diabetes mellitus (T2DM) is increasing globally. It is rarely noticed that the incidence of CRC is higher in patients with T2DM. What needs to be mentioned is that metformin, a commonly used clinical drug for T2DM, attracts scholars' attention because of its benefits in lowering the risk of developing CRC. Hence, we try to find the common grounds of initiation of T2DM and CRC and the reason why metformin reduces the risk of CRC in patients with T2DM. We noticed consistent changes of gut microbiota, such as elevated Bacteroides, Prevotella and Bifidobacterium and depressed Firmicutes and Lactobacillus. Furthermore, many studies in recent years have proved that the efficacy of metformin, such as improving blood glucose, depends on the gut microbiota. Coincidentally, the progression of CRC is inseparable from the contributions of gut microbiota. Therefore, we first proposed the concept of the metformin-gut microbiota-CRC (in T2DM) axis to explain the effect of metformin in reducing CRC in patients with T2DM. In this review, we elaborated the new concept and its potential clinical application value.