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Microbiota of newborn meconium is associated with maternal anxiety experienced during pregnancy.
Little is known about whether a mother's psychological state during pregnancy influences her offspring's microbiome. This study examined whether maternal anxiety, depression, and stress during pregnancy is associated with the diversity of meconium microbiome, the first internal discharge, in 75 newborns from an existing birth cohort study. The meconium microbiome was profiled using multibarcode16S rRNA sequencing at V3-V4 hypervariable region followed by taxonomic assignment to the green gene 16S references at 97% similarity and diversity analysis at the genus level. Results showed that the meconium contained diversified microbiota, and greater pregnancy-related anxiety was significantly associated with a less diverse meconium microbiota community (p = 0.001). At the specific taxa level, greater pregnancy-related anxiety was correlated with a lower level of the Enterococcaceae family (p = 2e-4, Spearman rho = -0.43). These findings support a significant role of prenatal maternal mood in the early-life bacteria colonization of their offspring.
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Food for Thought: The Role of Nutrition in Behavioral Health.
Nutrition is a core pillar of Lifestyle Medicine with growing relevance to mental and behavioral health. While traditionally emphasized for cardiometabolic disease prevention, emerging evidence demonstrates that dietary patterns directly influence mood, cognition, stress resilience, and emotional regulation. This article synthesizes current research on biological pathways linking food and mental health-including the gut-brain axis, microbiome diversity, neurotransmitter synthesis, inflammation, and dietary pattern interventions. A diverse and balanced microbiome, adequate intake of omega-3s, B vitamins, and trace minerals, and diets low in inflammatory foods support healthier brain signaling and improved emotional stability. Clinical trials show that Mediterranean and plant-forward diets reduce depressive symptoms, while micronutrient supplementation enhances attention, emotional regulation, and stress response across the lifespan. Nutrition is also a critical but underutilized component of substance use recovery and child and adolescent behavioral health. Cultural food traditions further shape well-being by reinforcing identity, belonging, and resilience. Integrating nutrition screening, counseling, and food-as-medicine interventions into behavioral health care can strengthen treatment outcomes, especially when aligned with culturally informed practices and community needs. Systems-level approaches-including policies addressing food insecurity and produce prescription programs-demonstrate meaningful improvements in mental health. Overall, nutrition represents a powerful, accessible, and culturally resonant strategy to support emotional, cognitive, and behavioral well-being.
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Serotonin type 3 receptor subunit gene polymorphisms associated with psychosomatic symptoms in irritable bowel syndrome: A multicenter retrospective study.
BACKGROUND: Single-nucleotide polymorphisms (SNPs) of the serotonin type 3 receptor subunit (HTR3) genes have been associated with psychosomatic symptoms, but it is not clear whether these associations exist in irritable bowel syndrome (IBS). AIM: To assess the association of HTR3 polymorphisms with depressive, anxiety, and somatization symptoms in individuals with IBS. METHODS: In this retrospective study, 623 participants with IBS were recruited from five specialty centers in Germany, Sweden, the United States, the United Kingdom, and Ireland. Depressive, anxiety, and somatization symptoms and sociodemographic characteristics were collected. Four functional SNPs - HTR3A c.-42C>T, HTR3B c.386A>C, HTR3C c.489C>A, and HTR3E c.*76G>A - were genotyped and analyzed using the dominant and recessive models. We also performed separate analyses for sex and IBS subtypes. SNP scores were calculated as the number of minor alleles of the SNPs above. The impact of HTR3C c.489C>A was tested by radioligand-binding and calcium influx assays. RESULTS: Depressive and anxiety symptoms significantly worsened with increasing numbers of minor HTR3C c.489C>A alleles in the dominant model (F depressive = 7.475, P depressive = 0.006; F anxiety = 6.535, P anxiety = 0.011). A higher SNP score (range 0-6) was linked to a worsened depressive symptoms score (F = 7.710, P-linear trend = 0.006) in IBS. The potential relevance of the HTR3C SNP was corroborated, showing changes in the expression level of 5-HT3AC variant receptors. CONCLUSION: We have provided the first evidence that HTR3C c.489C>A is involved in depressive and anxiety symptoms in individuals with IBS. The SNP score indicated that an increasing number of minor alleles is linked to the worsening of depressive symptoms in IBS.
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Sargassum pallidum reduces inflammation to exert antidepressant effect by regulating intestinal microbiome and ERK1/2/P38 signaling pathway.
Immune inflammation is one of the main factors in the pathogenesis of depression. It is an effective and active way to find more safe and effective anti-inflammatory depressant drugs from plant drugs. The purpose of this study is to explore the potential of marine plant Sargassum pallidum (Turn).C.Ag. (Haihaozi, HHZ) in the prevention and treatment of depression and to explain the related mechanism. Phytochemical analysis showed that alkaloids, terpenes, and organic acids are the main constituents. In vitro and in vivo activity studies showed the anti-neuroinflammatory and antidepressant effect of Sargassum pallidum, furthermore, confirmed that 7-Hydroxycoumarin, Scoparone, and Kaurenoic Acid are important plant metabolites in Sargasum pallidum for anti-neuroinflammation. Mechanism exploration showed that inhibition of ERK1/2/p38 inflammatory signaling pathway contributing to the antidepressant effect of Sargassum pallidum in reducing intestinal inflammatory levels. This study confirmed the value of Sargassum pallidum and its rich plant metabolites in anti-inflammatory depression, providing a new choice for the follow-up research and development of antidepressant drugs.
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Newer Therapeutics to Selectively Kill Clostridioides difficile and Restore the Microbiome.
BACKGROUND: The antibiotic ibezapolstat and the live biotherapeutic product live-JSLM are promising future approaches for treating Clostridioides difficile infection. Ibezapostat is a highly specific antibiotic for Clostridioides difficile, with minimal impact on the intestinal flora. Live-JSLM is designed to restore healthy intestinal microbiota, thus preventing recurrence of Clostridioides difficile infection. In this narrative review, we reviewed available data on ibezapostat and live-JSLM, considering that they are prototypes of two distinct, unique mechanisms of action against Clostridioides difficile. METHODS: Data sources: PubMed and SCOPUS databases were searched from 1 January 2012 to 15 November 2025. Original articles reporting data on ibezapolstat and live-JSLM were included. RESULTS: 31 studies were included. When compared to conventional anti-Clostridioides difficile antibiotics, ibezapolstat had a similar level of effectiveness and minimal impact on the gut microbiota. The available data confirm live-JSLM safety and efficacy in restoring the gut microbiota following the conclusion of the standard anti-Clostridioides difficile antibiotic regimen. CONCLUSIONS: The results on ibezapolstat efficacy are promising, but require confirmation in larger patient populations through double-blind, randomised phase III trials. In the near future, an integrated approach may enhance the management of Clostridioides difficile infection: starting with highly specific antibiotics, i.e., ibezapolstat, followed by microbiome-based therapies such as live-JSLM.
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Correction: Altered gut metabolome contributes to depression-like behaviors in rats exposed to chronic unpredictable mild stress.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Integrated Plasma Metabolomics and Gut Microbiota Analysis: The Intervention Effect of Jiawei Xiaoyao San on Liver Depression and Spleen Deficiency Liver Cancer Rats.
Primary liver cancer is the third most common malignancy, and hepatocellular carcinoma is its main subtype, with a high recurrence rate and high mortality. Intestinal microflora and metabolic disorders are present in most HCC patients. Traditional Chinese medicine (TCM) plays an important role in the composition of intestinal microorganisms and the transformation of active metabolites. Many scholars are trying to develop related drugs to assist in the treatment of liver cancer. In the preliminary study of the research group, it was found that the Jiawei Xiaoyao San has a certain therapeutic effect on liver cancer, but the specific mechanism is still unclear. Therefore, this study constructed a liver cancer rat model with liver stagnation and spleen deficiency, to explore the regulatory effect of Jiawei Xiaoyao San on plasma metabolites and intestinal microflora and to find the potential mechanism of Jiawei Xiaoyao San in the treatment of liver cancer. Plasma samples and fecal samples were collected from liver cancer rats with liver depression and spleen deficiency for microbiome 16S rDNA sequencing and metabolic ESI-QTRAP-MS/MS analysis. Various bioinformatics methods were used to analyze the dataset individually and in combination. The analysis and identification of plasma metabolomics showed that the intervention effect of Jiawei Xiaoyao San on liver cancer rats with liver depression and spleen deficiency was related to 11 differential metabolites and signal pathways such as primary bile acid biosynthesis, phenylalanine metabolism, pantothenate and COA biosynthesis, metabolic pathways, cholesterol metabolism, and bile secretion. Combined with fecal microbiological analysis, it was found that Jiawei Xiaoyao San could significantly change the composition of intestinal flora in liver cancer rates, increase beneficial bacteria, and reduce the composition of harmful bacteria. This study provides some experimental basis for the traditional Chinese medicine theory and clinical application of Jiawei Xiaoyao San in the adjuvant treatment of liver cancer. The potential mechanism may be to regulate metabolism and intestinal flora to play the role of regulating liver depression, activating blood, and detoxifying, to achieve the purpose of adjuvant treatment of liver cancer.
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Treating Depression with Transcutaneous Auricular Vagus Nerve Stimulation: State of the Art and Future Perspectives.
Depression is a highly prevalent disorder, and its treatment is far from satisfactory. There is an urgent need to develop a new treatment for depression. Although still at its early stage, transcutaneous auricular vagus nerve stimulation (taVNS) has shown promising potential for treating depression. In this article, we first summarize the results of clinical studies on the treatment effect of taVNS on depression. Then, we re-analyze a previous study to identify the specific symptoms taVNS can relieve as indicated by subscores of the 24-item Hamilton Depression Scale in patients with depression. We found that taVNS can significantly reduce multiple symptoms of depression patients, including anxiety, psychomotor retardation, sleep disturbance, and hopelessness. Next, we pose several hypotheses on the mechanism of taVNS treatment of depression, including directly and indirectly modulating the activity and connectivity of key brain regions involved in depression and mood regulation; inhibiting neuro-inflammatory sensitization; modulating hippocampal neurogenesis; and regulating the microbiome-brain-gut axis. Finally, we outline current challenges and lay out the future directions of taVNS treatment of depression, which include (1) intensively comparing stimulation parameters and "dose effect" (treatment frequency and duration) to maximize the treatment effect of taVNS; (2) exploring the effect of taVNS on disorders comorbid with depression (such as chronic pain disorders, cardiovascular disorder, and autism) to provide new "two-for-one" treatment approaches for patients with these disorders; and (3) applying multiple scale methods to explore the underlying mechanism of taVNS.
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Fecal microbiota transplantation repairs intestinal permeability and regulates the expression of 5-HT to influence alcohol-induced depression-like behaviors in C57BL/6J mice.
The epidemic of alcohol abuse affects millions of people worldwide. Relevant evidence supports the notion that the gut microbiota (GM) plays a crucial role in central nervous system (CNS) function, and its composition undergoes changes following alcohol consumption. Therefore, the purpose of this study was to investigate the effect of reconstructing the gut microbiota by fecal microbiota transplantation (FMT) on alcohol dependence. Here, we established an alcohol dependence model with C57BL/6J mice and proved that FMT treatment improved anxiety-like behavior and alcohol-seeking behavior in alcohol-dependent mice. Additionally, we found that the expression of the intestinal intercellular tight junction structure proteins ZO-1 and occludin was significantly increased after FMT. FMT repaired intestinal permeability in alcohol-dependent mice and decreased the levels of lipopolysaccharide (LPS) and proinflammatory factors. Moreover, the serotonin (5-hydroxytryptamine, 5-HT) content was significantly increased in alcohol-dependent mouse intestinal and brain tissues after receiving the fecal microbiome from healthy mice. 16S rRNA sequencing demonstrated that FMT markedly reshaped the composition of the gut microbiota and elicited changes in the intestinal barrier and 5-HT levels. Collectively, our results revealed that FMT has a palliative effect on alcohol dependence and explored the underlying mechanisms, which provides new strategies for the treatment of alcohol dependence.
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The Skin-Brain Axis in Psoriasis and Depression: Roles of Inflammation, Hormones, Neuroendocrine Pathways, Neuropeptides, and the Microbiome.
Psoriasis, a common chronic inflammatory skin disease affecting approximately 2-3% of the global population, frequently co-occurs with depression. This highly prevalent comorbidity significantly impairs patients' quality of life. Despite the substantial physical and mental health burden imposed by psoriatic depression, the underlying pathophysiological mechanisms connecting psoriasis and depression remain poorly understood. In this review, we explored several pathological processes that may contribute to psoriasis-associated depression, including immune cells dysregulations, hormones imbalances, hypothalamic-pituitary-adrenal (HPA) axis dysfunctions, neuropeptides expression abnormalities, and gut dysbiosis. The primary purpose of this review was to present a comprehensive overview of the pathogenic mechanisms linking psoriasis and depression. These insights may guide trans-disciplinary interventions aimed at both skin and mood symptoms.