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Reactive oxygen species-responsive prodrug nanomicelle-functionalized Lactobacillus rhamnosus probiotics for amplified therapy of ulcerative colitis.
Characterized by elevated reactive oxygen species (ROS) and disrupted gut flora, ulcerative colitis (UC) affects millions of patients worldwide. Probiotic therapy is commonly utilized in clinical practice to modulate intestinal flora and ameliorate colitis symptoms. Nonetheless, oral probiotics encounter challenges such as limited bioactivity, brief retention time, intricate pathological conditions, and singular efficacy. Here we designed plant-derived 18β-glycyrrhetinic acid (18β-GA) prodrug nanomicelles with ROS and inflammation-resolving capabilities, as well as anti-depressant effects, to protect probiotics and amplify their therapeutic effects in alleviating UC and UC-associated depression-like behaviors. Upon oral administration to UC lesion sites, prodrug nanomicelles can be dissociated by excessive ROS and release 18β-GA to attenuate colonic inflammatory responses and oxidative stress, which in turn provided a favorable microenvironment for LGG to repair intestinal barrier integrity and restore the gut microbiota. The synergistic therapeutic effects of STG nanomicelles and LGG alleviated UC-associated depression-like behavior by suppressing the activation of microglia and reducing neuroinflammation. This study introduces a promising strategy for oral nanomedicine with satisfactory therapeutic outcomes for the treatment of inflammatory diseases by integrating naturally derived small-molecule drugs with probiotics.
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Personality and Psychoneuroimmunology: A Systems Biology Perspective.
Research in psychoneuroimmunology (PNI) underscores the intricate connections within the "whole mind-body system." Personality plays a pivotal role, with specific traits linked to stress influencing neural behavior and psychophysiological disorders. Gene expression networks associated with personality affect neuronal plasticity, epigenetic processes, and adaptive behaviors, highlighting the importance of systems biology mechanisms. Systemic inflammation correlates with key personality traits. Understanding the roles of inflammatory and oxidative biomarkers in personality traits and disorders can help identify diagnostic and therapeutic targets for various diseases. Neurobiological features contribute to our understanding of personality disorders and related conditions. Personality traits are linked to distributed neuroendocrine networks, particularly the hypothalamic-pituitary-adrenal (HPA) axis, rather than localized brain areas. Correlations have also been identified between personality traits and thyroid hormones. Disrupted hypothalamic-pituitary-thyroid (HPT) axis functions may be associated with disease severity, depression, and distress, highlighting the need for comprehensive endocrinological and psychopathological evaluations. The gut-brain axis influences personality traits, emotions, stress, and social behaviors. Altered gut microbiota is common in psychiatric conditions, suggesting potential treatments targeting the microbiota. Chronic stress impacts cognitive functions and correlates with personality and mental health, emphasizing the need for comprehensive, multi-dimensional patient profiles for effective prevention and therapy. A biopsychosocial model integrating personality traits will advance personalized and systems medicine.
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Golden bifid might improve diarrhea-predominant irritable bowel syndrome via microbiota modulation.
OBJECTIVE: Gut microbiota might play a crucial role in the pathogenesis of irritable bowel syndrome (IBS), and probiotics supplement may be an effective treatment option. This study aims to explore the therapeutic effects of Golden bifid on the diarrhea-predominant IBS (IBS-D). METHODS: Twenty-one consecutive IBS-D patients were recruited based on Rome IV criteria. All patients took 2000 mg Golden bifid triple daily for 4 weeks. Gastrointestinal (GI) symptoms, psychological symptoms, small intestine bacterial overgrowth (SIBO) and fecal microbiota characteristics were evaluated in IBS-D patients before and after treatment. RESULTS: After 4-week treatment of Golden bifid, the GI symptoms such as abdominal pain (2.90 ± 1.04 vs. 1.90 ± 1.26, P = 0.002), abdominal distension (2.00 ± 1.34 vs. 1.29 ± 1.31, P = 0.007), diarrhea (3.24 ± 1.37 vs. 1.81 ± 1.21, P = 0.001), defecatory urgency (3.48 ± 1.03 vs. 2.33 ± 1.35, P = 0.000) and incomplete evacuation (2.71 ± 1.15 vs. 1.76 ± 1.26, P = 0.003) were significantly alleviated in IBS-D patients. The Self-Rating Depression Scale (SDS) decreased significantly (46.19 ± 11.36 vs. 43.33 ± 9.65, P = 0.041), and SIBO could be eradicated in 25% (4/16) of IBS-D patients with SIBO. Meanwhile, the abundance of Unclassified Lachnospiraceae and Dorea in genus level and Unclassified Lachnospiraceae, Bacterium Dorea, Bacterium Butyricicoccus and Dorea formicigenerans ATCC 27755 in species level were increased in fecal microbiota (P < 0.05). CONCLUSIONS: Golden bifid could improve most of GI symptoms and depressive symptoms in IBS-D patients and eradicate a small proportion of SIBO in those IBS-D patients with SIBO. What's more, Golden bifid could also modulate the fecal microbiota in IBS-D patients, which implied that the Golden bifid might improve IBS-D via microbiota modulation.
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Gut Microbiota Composition in Mid-Pregnancy Is Associated with Gestational Weight Gain but Not Prepregnancy Body Mass Index.
BACKGROUND: Pregnancy is a time of numerous hormonal, metabolic, and immunological changes for both the mother and the fetus. Furthermore, maternal gut microbiota composition (GMC) is altered during pregnancy. One major factor affecting GMC in pregnant and nonpregnant populations is obesity. The aim was to analyze associations between maternal overweight/obesity, as well as gestational weight gain (GWG) and GMC. Moreover, the modifying effect of depression and anxiety symptom scores on weight and GMC were investigated. METHODS: Study included 46 women from the FinnBrain Birth Cohort study, of which 36 were normal weight, and 11 overweight or obese according to their prepregnancy body mass index (BMI). Stool samples were collected in gestational week 24, and the GMC was sequenced with Illumina MiSeq approach. Hierarchical clustering was executed to illuminate group formation according to the GMC. The population was divided according to Firmicutes and Bacteroidetes dominance. Symptoms of depression, general anxiety, and pregnancy-related anxiety were measured by using standardized questionnaires. RESULTS: Excessive GWG was associated with distinct GMC in mid-pregnancy as measured by hierarchical clustering and grouping according to Firmicutes or Bacteroidetes dominance, with Bacteroidetes being prominent and Firmicutes being less prominent in the GMC among those with increased GWG. Reduced alpha diversity was observed among the Bacteroidetes-dominated subjects. There were no zero-order effects between the abundances of bacterial genera or phyla, alpha or beta diversity, and prepregnancy BMI or GWG. CONCLUSION: Bacteroidetes-dominated GMC in mid-pregnancy is associated with increased GWG and reduced alpha diversity.
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Gender-based differences in host behavior and gut microbiota composition in response to high fat diet and stress in a mouse model.
Obesity is associated with a high prevalence of mood disorders such as anxiety and depression. Both stress and high fat diet can alter the gut microbiota and contribute to obesity. To examine the interrelationships between obesity, stress, gut microbiota and mood disorders, obesity was induced in mice using a high fat diet, and the mice were subsequently stressed using a chronic unpredictable mild stress protocol. During the experiment, the composition of the gut microbiota was analyzed by 16 S rRNA gene high-throughput sequencing, and anxiety-like behaviors were measured. The results revealed distinct gender differences in the impacts of obesity and stress on anxiety-like behaviors, activity levels, and composition of the gut microbiota. Male mice were more vulnerable to the anxiogenic effects of the high fat diet, and obese male mice showed decreased locomotion activity in response to stress whereas obese female mice did not. In females, stress caused the gut microbiota of lean mice to more closely resemble that of obese mice. Taken together, these results suggest the importance of considering gender as a biological variable in studies on the role of gut microbiota in obesity-related mood disorders.
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Gut microbiota and neurological effects of glyphosate.
There are currently various concerns regarding certain environmental toxins and the possible impact they can have on developmental diseases. Glyphosate (Gly) is the most utilised herbicide in agriculture, although its widespread use is generating controversy in the scientific world because of its probable carcinogenic effect on human cells. Gly performs as an inhibitor of 5-enolpyruvylshikimate-3-phospate synthase (EPSP synthase), not only in plants, but also in bacteria. An inhibiting effect on EPSP synthase from intestinal microbiota has been reported, affecting mainly beneficial bacteria. To the contrary, Clostridium spp. and Salmonella strains are shown to be resistant to Gly. Consequently, researchers have suggested that Gly can cause dysbiosis, a phenomenon which is characterised by an imbalance between beneficial and pathogenic microorganisms. The overgrowth of bacteria such as clostridia generates high levels of noxious metabolites in the brain, which can contribute to the development of neurological deviations. This work reviews the impact of Gly-induced intestinal dysbiosis on the central nervous system, focusing on emotional, neurological and neurodegenerative disorders. A wide variety of factors were investigated in relation to brain-related changes, including highlighting genetic abnormalities, pregnancy-associated problems, diet, infections, vaccines and heavy metals. However, more studies are required to determine the implication of the most internationally used herbicide, Gly, in behavioural disorders.
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Review article: bugs, inflammation and mood-a microbiota-based approach to psychiatric symptoms in inflammatory bowel diseases.
BACKGROUND: Psychiatric co-morbidities including depression and anxiety are common in inflammatory bowel diseases (IBD). Emerging evidence suggests that interactions between the gut microbiota and brain may play a role in the pathogenesis of psychiatric symptoms in IBD. AIM: To review the literature on microbiota-brain-gut interactions in gut inflammation, psychosocial stress and mental disorders and to discuss the putative mediating role of gut microbiota in the development of psychiatric symptoms or co-morbidities in IBD. METHODS: A literature search was conducted on Ovid and Pubmed to select relevant animal and human studies reporting an association between IBD, mental disorders and gut microbiota. RESULTS: Gut microbial alterations are frequently reported in subjects with IBD and with mental disorders. Both have been associated with reduced faecal bacterial diversity, decreased taxa within the phylum Firmicutes and increased Gammaproteobacteria. In animal studies, microbial perturbations induce behavioural changes and modulate inflammation in mice. Anxiety- and depression-like behaviours in animals can be transferred via faecal microbiota. In humans, modulation of the gut microbiota with probiotics is associated with behavioural and mood changes. Recent data show correlations in changes of faecal and mucosal microbiota and psychological distress in patients with IBD independent of disease activity. CONCLUSION: Both IBD and mental disorders are associated with gut microbial alterations. Preclinical and preliminary human studies have shown a mediating role of the gut microbiota in intestinal inflammation and anxiety, depression and stress. Targeting the gut microbiota may represent a useful therapeutic approach for the treatment of psychiatric co-morbidities in IBD.
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Predicting response to the low FODMAP diet in irritable bowel syndrome: Current evidence and clinical considerations.
BACKGROUND AND OBJECTIVES: The low fermentable oligo-, di-, mono-saccharides and polyols (FODMAP) diet is an effective dietary intervention for irritable bowel syndrome (IBS), yet up to 50% of patients fail to re-spond adequately. Identifying reliable predictors of response could optimize treatment selection and improve treatment outcomes while avoiding unnecessary dietary restrictions. This narrative review examines current evidence for predictors of response to the low FODMAP diet and highlights gaps in knowledge that must be addressed to develop clinically useful indicators for routine practice. METHODS AND STUDY DESIGN: We re-viewed the literature on the low FODMAP diet, and studies investigating factors that may predict treatment response, including clinical, diagnostic, biological, biochemical, and microbial markers. RESULTS: Several po-tential predictors to the low FODMAP diet have emerged, including baseline symptom severity, psychological factors (particularly depression), hydrogen breath test results, volatile organic compounds in fecal samples, and specific gut microbiota profiles. Clinical and psychological measures show the most immediate potential for implementation due to accessibility and established measurement tools. Biological markers, including breath testing, metabolomics, and microbiome analysis, show promise but require further validation in larger, diverse populations and standardization of methodologies. CONCLUSIONS: Despite promising research, signifi-cant gaps remain in developing reliable, accessible predictors of response to the low FODMAP diet. Future research should focus on validating simple clinical tools that combine symptom profiles with psychological assessment to guide treatment decisions. A personalized approach to dietary management of IBS based on reliable response predictors would optimize clinical outcomes while minimizing unnecessary dietary restriction and healthcare resource utilization.
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Development and application of bio-sample quantification to evaluate stability and pharmacokinetics of inulin-type fructo-oligosaccharides from Morinda Officinalis.
Inulin-type fructooligosaccharides (FOS) purified from Morinda Officinalis, with degrees of polymerization (DP) from 3 to 9, have been approved in China as an oral prescribed drug for mild and moderate depression episode, while the stability and oral absorption of this FOS mixtures are largely unknown. As the main active component and quality control marker for above FOS, DP5 was selected as the representative FOS in this study. Desalting method by ion exchange resin was developed to treat bio-sample, followed by separation and quantification by high performance liquid chromatography-charged aerosol detector. Results showed that the DP5 was stepwisely hydrolyzed in simulated gastric fluid and gut microbiota, while maintained stable in intestinal fluid. DP5 has poor permeability across Caco-2 monolayer with Papp of 5.22 × 10-7 cm/s, and very poor oral absorption with bioavailability of (0.50 ± 0.12)% in rat. In conclusion, FOS in Morinda Officinalis demonstrated poor chemical stability in simulated gastric fluid and human gut microbiota, and low oral absorption in rats.
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Bidirectional regulation of stress responses by the microbiota-gut-brain axis: Molecular mechanisms and therapeutic perspectives.
The bidirectional interaction between the gut microbiota and the CNS, referred to as the microbiota-gut-brain axis, has gained recognition as a key regulator of stress responses and neuropsychiatric health. This review synthesizes evidence from preclinical and human studies conducted between 2010 and 2026, setting itself apart from previous reviews by focusing on the bidirectional connection between stress exposure and alterations in gut microbiota. It places particular emphasis on the molecular mechanisms involved, such as neuroinflammation, regulation of the HPA axis, neurotransmitter signaling, and how the microbiota contributes to stress adaptation. Growing evidence from preclinical and clinical research suggests that stress-induced disturbances in gut microbial composition can trigger systemic and neuroinflammation. This occurs through mechanisms such as increased intestinal permeability, translocation of lipopolysaccharides, and activation of TLR4 and NF-κB signaling pathways. Consequently, these immune disruptions adversely affect neurotrophic and neurotransmitter systems such as brain-derived neurotrophic factor (BDNF), serotonin, dopamine, and GABA contributing to anxiety, depression, cognitive impairments, and neurodegenerative conditions. Instead, deliberate modulation of the gut microbiota through probiotics, psychobiotics, fermented foods, and dietary strategies has shown potential to restore microbial balance. Such interventions can help reduce overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, reduce levels of IL-6 and TNF-α, and promote BDNF-driven neuroplasticity. Experimental studies highlight how specific bacterial strains may influence outcomes under stress by enhancing CREB phosphorylation, maintaining tight junction integrity in the gut, and modulating microglial activation. Emerging therapeutic approaches such as fecal microbiota transplantation and postbiotic metabolites, including SCFAs, have also demonstrated promising potential for clinical translation.