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Psychobiotics and the microbiota-gut-brain axis: Emerging paradigms in mental health modulation.
The global rise in mental health conditions has prompted interest in interventions that act beyond conventional psychopharmacology. Psychobiotics, broadly understood as live microorganisms or microbe-derived products that interact with the microbiota-gut-brain axis, have been suggested to exert neuroactive effects through neural, immune, endocrine and metabolic routes. This narrative review synthesizes recent preclinical, mechanistic and early clinical observations. Experimental studies show that selected strains can modulate cytokine signalling, influence stress-responsive systems such as the hypothalamic-pituitary-adrenal axis, and support synaptic plasticity via factors such as brain-derived neurotrophic factor. A limited number of human trials using well-characterized Lactobacillus and Bifidobacterium strains have reported improvements in affective and stress-related outcomes, but these effects are generally small to moderate, more apparent in adjunctive than stand-alone use, and dependent on strain, dose, population and intervention length (typically 4-12 weeks). Evidence on neurodevelopmental conditions (e.g., autism spectrum disorder, attention-deficit/hyperactivity disorder) remains preliminary, based on small and heterogeneous samples. Across studies, key constraints include methodological heterogeneity, incomplete strain-level reporting, and gaps in mechanistic resolution that make it difficult to link microbial shifts to psychiatric benefit. Emerging microbiome- and metabolomics-informed approaches may help identify likely responders and improve translational precision, but they are not yet ready for routine clinical application. Overall, psychobiotics should currently be viewed as a promising adjunct within integrative mental health care, warranting larger, standardized trials with clearly defined strains, doses and mechanistic endpoints.
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Do your gut microbes affect your brain dopamine?
Increasing evidence shows changes in gut microbiota composition in association with psychiatric disorders, including anxiety and depression. Moreover, it has been reported that perturbations in gut microbe diversity and richness influence serotonergic, GABAergic, noradrenergic, and dopaminergic neurotransmission. Among these, dopamine is regarded as a main regulator of cognitive functions such as decision making, attention, memory, motivation, and reward. In this work, we will highlight findings that link alterations in intestinal microbiota and dopaminergic neurotransmission, with a particular emphasis on the mesocorticolimbic circuit, which is involved in reward to natural reinforcers, as well as abuse substances. For this, we reviewed evidence from studies carried out on germ-free animals, or in rodents subjected to intestinal dysbiosis using antibiotics, and also through the use of probiotics. All this evidence strongly supports that the microbiota-gut-brain axis is key to the physiopathology of several neuropsychiatric disorders involving those where dopaminergic neurotransmission is compromised. In addition, the gut microbiota appears as a key player when it comes to proposing novel strategies to the treatment of these psychiatric conditions.
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The gut-brain axis: role of gut microbiota in neurological disease pathogenesis and pharmacotherapeutics.
The gut-brain axis is a highly complex, bidirectional communication link between the gut and the central nervous system (CNS), mainly through neural, endocrine, immunological, and metabolic pathways. This review outlines the growing contribution of gut microbiota in the remediation of neurological health and also emphasizes the controlling role of gut microbiota on the synthesis of neurotransmitters. Emerging evidence indicates that dysbiosis of the gut is related to a variety of neurodegenerative and neuropsychiatric diseases such as Parkinson's disease (PD), Alzheimer's disease (AD), multiple sclerosis (MS), amyotrophic lateral sclerosis (ALS), Huntington's disease (HD), autism spectrum disorders (ASD), depression, and glioblastoma. Mechanistic understandings show that gut microbes critically contribute to neuroimmune and blood-brain barrier (BBB) signaling. The peripheral association of gut microflora, networked with inflammasome activation, nuclear factor kappa B (NF-κB), and type-I IFN pathways highlights their role in CNS inflammation. Microbiota-targeted interventions with probiotics, prebiotics, synbiotics, antibiotics, dietary modifications, and fecal microbiota transplantation are examined for their therapeutic potential. These strategies appear to be promising to reinstate microbial balance, enhance neuroplastic responses, and ameliorate the disease symptoms. The review highlights personalized microbiome-based algorithms, underpinned by integrated multi-omics technologies and machine-learning-driven diagnostics. Future research should address underlying microbial mechanisms and perform large, randomized controlled trials in order to establish microbiota-based therapies for neurological disorders.
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Probiotics and the Microbiota-Gut-Brain Axis: Focus on Psychiatry.
PURPOSE OF REVIEW: Probiotics are living bacteria, which when ingested in adequate amounts, confer health benefits. Gut microbes are suggested to play a role in many psychiatric disorders and could be a potential therapeutic target. Between the gut and the brain, there is a bi-directional communication pathway called the microbiota-gut-brain axis. The purpose of this review is to examine data from recent interventional studies focusing on probiotics and the gut-brain axis for the treatment of depression, anxiety and schizophrenia. RECENT FINDINGS: Probiotics are likely to improve depression but not schizophrenia. Regarding anxiety, there is only one trial which showed an effect of a multispecies probiotic. However, determinants like the duration of treatment, dosage and interactions have not been thoroughly investigated and deserve more scientific attention. Microbiome-based therapies such as probiotics could be cautiously recommended for depression to enhance beneficial bacteria in the gut and to improve mood through the gut-brain axis.
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Short-term hot spring balneotherapy ameliorates sleep disorders: wrist-worn wearable-assessed sleep improvement associated with neuroimmune, tryptophan metabolic and gut microbiome alterations.
Balneotherapy is a potential complementary approach for sleep problems, but its short-term sleep effects and accompanying biological changes remain unclear. We conducted a prospective single-arm, self-controlled pilot study of 30 adults with sleep disorders, who completed a 10-day residential hot spring balneotherapy program (twice daily at 09:00 and 20:00, 30 min per session, 40-42 °C) at Tianhe Hot Spring, Sichuan Province, residing on-site and receiving identical meals throughout the intervention. Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and wrist-worn wearable tracking. Serum neurotransmitters, inflammatory cytokines and tryptophan-kynurenine metabolites were assayed, while 16 S rRNA-based gut microbiota profiles were profiled pre- and post-intervention. Post-intervention, PSQI scores decreased, while wearable metrics indicated longer total and nocturnal sleep duration, elevated deep-sleep duration and proportion, better sleep continuity, and a lower rapid eye movement (REM) percentage (P < 0.05). Blood pressure, anxiety/depression scores, and wearable-derived sleep-stress indices also improved. Biomarker profiling revealed elevated GABA, 5-HT, 5-HIAA, BDNF, and IL-10, alongside reduced IL-1β, IL-6, and TNF-α (P < 0.05). Trp metabolism shifted, characterized by decreased Trp and increased 3-HAA and PA (P < 0.05). Structurally, the gut microbiota exhibited an increased abundance of Blautia_A (P < 0.05), with LEfSe analysis identifying post-intervention enrichment of Turicibacter and pre-intervention predominance of Agathobacter. Cross-system network analysis further established 5-HT, IL-6, and IL-10 as the core candidate biomarker profile directly correlating with these multi-domain sleep improvements. Overall, short-term residential hot spring balneotherapy may improve subjective and wearable-derived sleep outcomes, accompanied by coordinated cardiovascular, stress-related, neuroimmune, tryptophan-metabolic, and gut microbiome changes, supporting a multi-system physiological basis for balneotherapy-related sleep improvement.
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The role of the microbiome on immune homeostasis of the host nervous system.
The gut microbiota is often termed the "second genome" of the human body. It has been shown to be one of the most significant environmental factors (non-genetic) influencing the onset, progression, and prognosis of various neurological and psychiatric disorders through its interactions with the host immune, nervous, and endocrine systems. Changes in the function and composition of the gut microbiota are strongly associated with amyotrophic lateral sclerosis, autism spectrum disorder, depression, Parkinson's disease, and Alzheimer's disease. This review summarizes the research regarding the associations and regulatory mechanisms between the gut microbiota and the central nervous system in order to explore the role of the gut microbiota in maintaining neural homeostasis.
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Oral sodium butyrate supplementation ameliorates paclitaxel-induced behavioral and intestinal dysfunction.
Paclitaxel (PTX) is one of the most broadly used chemotherapeutic agents for the treatment of several tumor types including ovarian, breast, and non-small cell lung cancer. However, its use is limited by debilitating side effects, involving both gastrointestinal and behavioral dysfunctions. Due to growing evidence showing a link between impaired gut function and chemotherapy-associated behavioral changes, the aim of this study was to identify a novel therapeutic approach to manage PTX-induced gut and brain comorbidities. Mice were pre-treated with sodium butyrate (BuNa) for 30 days before receiving PTX. After 14 days, mice underwent to behavioral analysis and biochemical investigations of gut barrier integrity and microbiota composition. Paired evaluations of gut functions revealed that the treatment with BuNa restored PTX-induced altered gut barrier integrity, microbiota composition and food intake suggesting a gut-to-brain communication. The treatment with BuNa also ameliorated depressive- and anxiety-like behaviors induced by PTX in mice, and these effects were associated with neuroprotective and anti-inflammatory outcomes. These results propose that diet supplementation with this safe postbiotic might be considered when managing PTX-induced central side effects during cancer therapy.
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The Relationship Between Perinatal Mental Health and Stress: a Review of the Microbiome.
PURPOSE OF REVIEW: Our current understanding of the underlying mechanisms and etiologies of perinatal mood and anxiety disorders (PMADs) is not clearly identified. The relationship of stress-induced adaptations (i.e., the hypothalamic-pituitary-adrenal (HPA) axis, the autonomic nervous system (ANS), the immune system) and the microbiota are potential contributors to psychopathology exhibited in women during pregnancy and postpartum and should be investigated. RECENT FINDINGS: The stress response activates the HPA axis and dysregulates the ANS, leading to the inhibition of the parasympathetic system. Sustained high levels of cortisol, reduced heart variability, and modulated immune responses increase the vulnerability to PMAD. Bidirectional communication between the nervous system and the microbiota is an important factor to alter host homeostasis and development of PMAD. Future research in the relationship between the psychoneuroimmune system, the gut microbiota, and PMAD has the potential to be integrated in clinical practice to improve screening, diagnosis, and treatment.
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Gut feeling: Exploring the intertwined trilateral nexus of gut microbiota, sex hormones, and mental health.
The complex interplay between the gut microbiota, sex hormones, and mental health is emerging as a pivotal factor in understanding and managing psychiatric disorders. Beyond their traditional roles, sex hormones exert profound effects on various physiological systems including the gut microbiota. Fluctuations in sex hormone levels, notably during the menstrual cycle, influence gut physiology and barrier function, shaping gut microbiota composition and immune responses. Conversely, the gut microbiota actively modulates sex hormone levels via enzymatic processes. This bidirectional relationship underscores the significance of the gut-brain axis in maintaining mental well-being. This review explores the multifaceted interactions between sex hormones, the gut microbiota, and mental health outcomes. We highlight the potential of personalized interventions in treating psychiatric disorders, particularly in vulnerable populations such as premenopausal women and individuals with depressive disorders. By elucidating these complex interactions, we aim to provide insights for future research into targeted interventions, enhancing mental health outcomes.
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Colon impairments and inflammation driven by an altered gut microbiota leads to social behavior deficits rescued by hyaluronic acid and celecoxib.
BACKGROUND: The exact mechanisms linking the gut microbiota and social behavior are still under investigation. We aimed to explore the role of the gut microbiota in shaping social behavior deficits using selectively bred mice possessing dominant (Dom) or submissive (Sub) behavior features. Sub mice exhibit asocial, depressive- and anxiety-like behaviors, as well as systemic inflammation, all of which are shaped by their impaired gut microbiota composition. METHODS: An age-dependent comparative analysis of the gut microbiota composition of Dom and Sub mice was performed using 16S rRNA sequencing, from early infancy to adulthood. Dom and Sub gastrointestinal (GI) tract anatomy, function, and immune profiling analyses were performed using histology, RT-PCR, flow cytometry, cytokine array, and dextran-FITC permeability assays. Short chain fatty acids (SCFA) levels in the colons of Dom and Sub mice were quantified using targeted metabolomics. To support our findings, adult Sub mice were orally treated with hyaluronic acid (HA) (30 mg/kg) or with the non-steroidal anti-inflammatory agent celecoxib (16 mg/kg). RESULTS: We demonstrate that from early infancy the Sub mouse gut microbiota lacks essential bacteria for immune maturation, including Lactobacillus and Bifidobacterium genera. Furthermore, from birth, Sub mice possess a thicker colon mucin layer, and from early adulthood, they exhibit shorter colonic length, altered colon integrity with increased gut permeability, reduced SCFA levels and decreased regulatory T-cells, compared to Dom mice. Therapeutic intervention in adult Sub mice treated with HA, celecoxib, or both agents, rescued Sub mice phenotypes. HA treatment reduced Sub mouse gut permeability, increased colon length, and improved mouse social behavior deficits. Treatment with celecoxib increased sociability, reduced depressive- and anxiety-like behaviors, and increased colon length, and a combined treatment resulted in similar effects as celecoxib administered as a single agent. CONCLUSIONS: Overall, our data suggest that treating colon inflammation and decreasing gut permeability can restore gut physiology and prevent social deficits later in life. These findings provide critical insights into the importance of early life gut microbiota in shaping gut immunity, functionality, and social behavior, and may be beneficial for the development of future therapeutic strategies.