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The effects of a semen cuscutae flavonoids-based antidepressant treatment on microbiome and metabolome in mice.
BACKGROUND: Depression is a prevalent psychiatric disorder and one of the leading causes of disability worldwide. Previous studies have shown that Semen Cuscutae flavonoids (SCFs) exert antidepressant effects by modulating the microbiota-neuroinflammation axis and ameliorating hippocampal metabolic disturbances. However, the impact of SCFs on gut microbiota and related metabolomics remains largely undefined. Given that the gut microbiota has been proven to play a significant role in the etiology of depression and serves as a promising target for its treatment in humans, this study aims to elucidate the antidepressant effects of SCFs and to investigate how they modulate microbial and metabolic pathways to alleviate depressive symptoms. MATERIALS AND METHODS: Chronic unpredictable mild stress (CUMS)-induced mice were used as a depression model. The normal mice and CUMS-induced mice were treated with either vehicle or with SCFs. A range of standardized behavioral assays and physiological indicators were employed to evaluate the antidepressant effects of SCFs. Upon the confirmation of the effectiveness of the SCFs treatment, the composition, richness, and diversity of the fecal microbiota were assessed using 16S rRNA gene sequencing. Additionally, fecal metabolic profiling was analyzed using UHPLC-MS/MS-based metabolomics. Multivariate data analysis was subsequently performed to identify differential metabolites and characterize alterations in fecal metabolites. Furthermore, a correlation analysis between differential metabolites and key microbiota was conducted. RESULTS: SCFs significantly ameliorated depressive behaviors and the dysregulated diversity of fecal microbiota induced by CUMS. SCFs enhanced the gut microbiota structure in the CUMS group by increasing the Firmicutes/Bacteroidota ratio, significantly elevating the abundance of Firmicutes, Lactobacillus, Limosilactobacillus, and Actinobacteria while reducing the abundance of Bacteroidota and Bacteroides in CUMS-treated mice. Fecal metabolomics analyses revealed that SCFs could modulate metabolic pathways, including aldosterone synthesis and secretion, arachidonic acid metabolism, and primary bile acid biosynthesis. CONCLUSIONS: Mice with depression induced by CUMS exhibited disturbances in both their gut microbiota and fecal metabolism. However, SCFs restored the balance of the microbial community and corrected metabolic disturbances in feces, exerting antidepressant effects through a multifaceted mechanism.
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Efficacy and Safety of Limosilactobacillus reuteri DSM 17938 in Infantile Colic: A Narrative Review From Pathogenesis to Clinical Practice.
Infantile colic is one of the most common functional gastrointestinal disorders, affecting approximately 20% of infants worldwide. Characterized by paroxysmal episodes of inconsolable crying and fussing without an obvious cause, the condition imposes a significant psychosocial burden on the family unit, acting as a primary trigger for maternal postpartum depression, parental exhaustion, and premature cessation of breastfeeding. Despite its prevalence, traditional management in primary care remains heterogeneous and often ineffective, leaving a substantial therapeutic gap. Emerging research has identified gut dysbiosis as a cornerstone of its pathogenesis, where an imbalance in early microbial colonization, characterized by reduced diversity and a higher prevalence of gas-producing coliforms, triggers intestinal inflammation and visceral hypersensitivity through the gut-brain axis. This narrative review synthesizes the current clinical evidence regarding the efficacy and safety of Limosilactobacillus reuteri DSM 17938 in the management of infantile colic. This specific probiotic strain exerts its therapeutic effects through multifaceted mechanisms, including the production of the antimicrobial metabolite reuterin, the modulation of gastrointestinal motility via microvesicles, and the reduction of low-grade gut inflammation. Clinical evidence from large-scale meta-analyses confirms that L. reuteri DSM 17938 is significantly superior to placebo, particularly in breastfed infants, where it is twice as likely to achieve a 50% reduction in crying time within 14-21 days of treatment. However, its efficacy appears less predictable in formula-fed populations, potentially due to the absence of synergistic factors found in human milk. Clinical management in primary care should prioritize a rigorous diagnostic approach to rule out organic causes through a detailed physical examination and the application of the Rome IV criteria. The cornerstone of non-pharmacological management remains empathetic parental reassurance and education to mitigate the risk of infant abuse and support family well-being. When probiotic intervention is indicated, L. reuteri DSM 17938 represents a robust, evidence-based first-line therapy for healthy, full-term infants. Regarding safety, this strain maintains an excellent profile supported by its generally recognized as safe (GRAS) status, with no significant adverse effects reported in healthy populations. Nevertheless, recent clinical scrutiny emphasizes the need for caution and the use of pharmaceutical-grade products in vulnerable groups. Ultimately, L. reuteri DSM 17938 addresses both the biological triggers of colic and the psychosocial stability of the family unit.
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Sex- and Gender-Related Differences in Common Functional Gastroenterologic Disorders.
Functional gastrointestinal (GI) disorders (FGIDs) result from central and peripheral mechanisms, cause chronic remitting-relapsing symptoms, and are associated with comorbid conditions and impaired quality of life. This article reviews sex- and gender-based differences in the prevalence, pathophysiologic factors, clinical characteristics, and management of functional dyspepsia (FD) and irritable bowel syndrome (IBS) that together affect approximately 1 in 4 people in the United States. These conditions are more common in women. Among patients with IBS, women are more likely to have severe symptoms and coexistent anxiety or depression; constipation or bloating and diarrhea are more common in women and men, respectively, perhaps partly because defecatory disorders, which cause constipation, are more common in women. Current concepts suggest that biological disturbances (eg, persistent mucosal inflammation after acute gastroenteritis) interact with other environmental factors (eg, abuse) and psychological stressors, which influence the brain and gut to alter GI tract motility or sensation, thereby causing symptoms. By comparison to a considerable understanding of sex-based differences in the pathogenesis of visceral hypersensitivity in animal models, we know less about the contribution of these differences to FGID in humans. Slow gastric emptying and colon transit are more common in healthy women than in men, but effects of gonadal hormones on colon transit are less important than in rodents. Although increased visceral sensation partly explains symptoms, the effects of sex on visceral sensation, colonic permeability, and the gut microbiome are less prominent in humans than rodents. Whether sex or gender affects response to medications or behavioral therapy in FD or IBS is unclear because most patients in these studies are women.
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Depression and the Aberrant Intestinal Microbiome.
Depression is one of the most common mental health disorders affecting adults in the United States. The current treatment is the combination of pharmacotherapy and psychotherapy. Recently, the evidence linking gut microbiome dysregulation to the development of depression has grown. The pathophysiology is currently poorly understood, although leading hypotheses include involvement of the hypothalamic-pituitary-adrenal axis, a bidirectional relationship between the gut microbiome and the central nervous system, and production of signaling molecules by the gut microbiome. Available and emerging treatments of the aberrant microbiome include antidepressants, antibiotics, diet modification, probiotics, and fecal microbiota transplant. This article explores the interconnectivity of gut microbiota and depression and treatments targeted toward the gut, reviews the gastroenterologist's potential role in managing gut dysbiosis in patients with depression, and highlights research topics to be addressed to create evidence-based guidelines.
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Randomized controlled trial comparing the impacts of Saccharomyces boulardii and Lactobacillus rhamnosus OF44 on intestinal flora in cerebral palsy rats: insights into inflammation biomarkers and depression-like behaviors.
BACKGROUND: Cerebral palsy (CP) is a unique neurological disorder which adversely affects motion. Cytokines and gut microbial composition contribute to CP and other diseases, such as reproductive tract inflammation and bone loss. Importantly, Saccharomyces boulardii (S. boulardii) reduces the degree of inflammation and improves overall health status. As our previous study showed that Lactobacillus rhamnosus (L. rhamnosus) OF44, a selected strain of gut bacteria originally used to treat reproductive tract inflammation and bone loss, has effects similar to that of S. boulardii, we decided to use L. rhamnosus OF44 on CP rats. Validation of the effects of L. rhamnosus OF44 on CP adds to its confirmed effects in treating osteoporosis and reproductive tract microbiota disorders, increasing its potential as a probiotic. The purpose of this was to ascertain whether L. rhamnosus OF44 can alleviate the symptoms of CP. METHODS: CP rat models were created through left carotid artery ligation. Following this, 100-day old CP rats were exposed to L. rhamnosus OF44, S. boulardii, or normal saline gastric gavage daily for 28 days. Grouping of the rats is determined randomly. Before and after the gavage, behavioral experiments were conducted and the inflammation levels assessed via measurements of interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) inflammatory markers. The efficacy of the outcome is measured by performing statistical analysis like the t-test on the data to see its significance. Additionally, variations inside gut microbiome were evaluated via 16S ribosomal RNA sequencing. RESULTS: Before intervention, CP rats failed to exhibit depression-like behavior (P=0.6). L. rhamnosus OF44 treatment significantly reduced the level of IL-6 (P=4.8e-05), S. boulardii treatment significantly reduced the level of TNF-α (P=0.04). In addition, both treatments altered the composition and complexity of the gut microbiome. CONCLUSIONS: Our results indicated that L. rhamnosus OF44 has potential in alleviating inflammation and altering the gut microbial composition in CP, and that it has the potential to clinically treat CP. There are some limitations of this study. For example, dietary differences and their effects on gastrointestinal dysfunction are not considered in this study, and only two behavioral experiments were used.
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The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention.
The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and stroke-including post-stroke cognitive impairment (PSCI), as well as major depressive disorder (MDD), bipolar disorder (BD), anxiety disorders, post-traumatic stress disorder (PTSD), and chronic fatigue syndrome (CFS). Common findings include reduced microbial diversity, depletion of short-chain fatty acid (SCFA)-producing genera, and enrichment of pro-inflammatory taxa. These changes contribute to neuroinflammation, blood-brain barrier (BBB) dysfunction, microglial activation, and neurotransmitter imbalances. The review further explores the neurotoxic effects of external factors such as radiation and xenobiotics on the MGBA. Despite disorder-specific variations, shared microbial and immunological mechanisms emerge across the spectrum of conditions. Importantly, we present current and emerging strategies aimed at restoring gut-brain communication, including dietary interventions such as fiber-rich and Mediterranean diets, SCFA supplementation, probiotics, and fecal microbiota transplantation (FMT). These approaches show promise in alleviating cognitive and emotional symptoms, modulating immune responses, and potentially slowing disease progression. By integrating mechanistic insights with therapeutic perspectives, this review underscores the gut microbiota as a modifiable factor in neuropsychiatric and neurodegenerative disease. Targeting the MGBA offers a novel, translational approach to intervention that may ultimately contribute to healthier brain aging and improved outcomes across the lifespan.
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The Impact of Early-Life Cecal Microbiota Transplantation on Social Stress and Injurious Behaviors in Egg-Laying Chickens.
Injurious behaviors (i.e., aggressive pecking, feather pecking, and cannibalism) in laying hens are a critical issue facing the egg industry due to increased social stress and related health and welfare issues as well as economic losses. In humans, stress-induced dysbiosis increases gut permeability, releasing various neuroactive factors, causing neuroinflammation and related neuropsychiatric disorders via the microbiota-gut-brain axis, and consequently increasing the frequency and intensity of aggression and violent behaviors. Restoration of the imbalanced gut microbial composition has become a novel treatment strategy for mental illnesses, such as depression, anxiety, bipolar disorder, schizophrenia, impulsivity, and compulsivity. A similar function of modulating gut microbial composition following stress challenge may be present in egg-laying chickens. The avian cecum, as a multi-purpose organ, has the greatest bacterial biodiversity (bacterial diversity, richness, and species composition) along the gastrointestinal tract, with vitally important functions in maintaining physiological and behavioral homeostasis, especially during the periods of stress. To identify the effects of the gut microbiome on injurious behaviors in egg-laying chickens, we have designed and tested the effects of transferring cecal contents from two divergently selected inbred chicken lines on social stress and stress-related injurious behaviors in recipient chicks of a commercial layer strain. This article reports the outcomes from a multi-year study on the modification of gut microbiota composition to reduce injurious behaviors in egg-laying chickens. An important discovery of this corpus of experiments is that injurious behaviors in chickens can be reduced or inhibited through modifying the gut microbiota composition and brain serotonergic activities via the gut-brain axis, without donor-recipient genetic effects.
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Gut microbiome dysbiosis and alterations in kynurenine pathway of tryptophan metabolism are associated with depression in people with HIV.
BACKGROUND: People with HIV have increased risk of depression and differed gut microbiome composition. While alterations in gut microbiome and kynurenine pathway of tryptophan metabolism have each been independently linked to depression in the general population, their interrelationships in people with HIV remain unclear. METHODS: People with HIV with available gut microbiome data and depression assessments were included (n = 365). We assessed the associations between gut microbiome, evidence of depression, kynurenine metabolites, inflammatory markers, clinical variables. RESULTS: Individuals with evidence of depression (n = 32) had significantly higher plasma levels of IL-6 and quinolinic acid, along with altered gut microbiome composition (dysbiosis), compared to individuals without evidence of depression (n = 333). No statistically significant correlation was found between depression-related gut microbial dysbiosis and levels of kynurenine metabolites or inflammatory markers, whereas the latter two correlated with each other. Mediation analysis further showed a borderline but not statistically significant indirect effect of kynurenine and quinolinic acid levels on depression through inflammatory marker IL-6. CONCLUSIONS: Our data show that gut microbiome dysbiosis is associated with depression in people with HIV, but not with the altered kynurenine metabolites linked to depression. These findings suggest distinct pathways linking gut microbiome dysbiosis and alterations in kynurenine pathway of tryptophan metabolism to depression.
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Integrated 16S rRNA sequencing and metabolomics analysis to investigate the antidepressant role of Yang-Xin-Jie-Yu decoction on microbe-gut-metabolite in chronic unpredictable mild stress-induced depression rat model.
Objectives: Our goals were to evaluate the antidepressant efficacy of Yang-Xin-Jie-Yu Decoction (YXJYD) in Chronic Unpredictable Mild Stress (CUMS)-induced depression rat model and to investigate the underlying mechanisms. Design: We used CUMS-induced depression rat model to evaluate whether oral administration of YXJYD with different doses (2.1 g/kg, 1.05 g/kg and 0.525 g/kg, respectively) improve the depressive-like symptoms, and then performed UHPLC-Q-TOF-MS to explore the active ingredients of YXJYD. Subsequently, rat's cecal contents, serum, and urine were collected from the control group, CUMS model group, and YXJYD high-dose (2.1 g/kg) treatment group. The 16S rRNA sequencing was performed on the cecal contents, based on Illumina MiSeq platform, and ANOVA analysis were used to analyze the composition variety and screen differential expression of gut bacteria in the three groups. 1H Nuclear Magnetic Resonance (NMR) analysis was used for analyzing the metabolites obtained from cecal contents, serum, and urine, and KEGG enrichment analysis was used to identify pathways of differential metabolites. An integrated 16S rRNA sequencing and metabolomic data were conducted to characterize the underlying mechanisms of YXJYD Results: The gut microbial communities, and serum, cecal content, urine metabolic compositions were significantly significantly altered in CUMS-induced depressive rats, while YXJYD effectively ameliorated the CUMS-associated gut microbiota dysbiosis, especially of Monoglobus, and alleviated the disturbance of serum, cecal content, urine metabolome and reversed the changes of key depressive and gut microbiota-related metabolites, such as succinic acid, taurine, hippuric acid, melatonin. With an integrated study of the gut microbiota and metabolomes, we identified the pathway of tricarboxylic acid cycle (TCA cycle) and propanoate metabolism as the regulated target of YXJYD on host-microbiome interaction. Conclusion: Our findings further confirmed the imbalance of metabolism and intestinal microbial is closely related to CUMS-induced depression. YXJYD regulates gut microbiome to affect body metabolomes and then produce antidepressant-like effect in CUMS-induced depressive rats while its molecular mechanism possibly be increased Monoglobus abundance in gut microbiota and regulated the TCA cycle pathway and propanoate metabolism in host.
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Microbiome-The Missing Link in the Gut-Brain Axis: Focus on Its Role in Gastrointestinal and Mental Health.
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine, and immunological mechanisms. There is mounting data that gut microbiota is the source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in the control of emotions, cognition, and physical activity. Most GI diseases are associated with altered transmission within the GBA that are influenced by both genetic and environmental factors. Current treatment protocols for GI and non-GI disorders may positively or adversely affect the composition of intestinal microbiota with a diverse impact on therapeutic outcome(s). Alterations of gut microbiota have been associated with mood and depressive disorders. Moreover, mental health is frequently affected in GI and non-GI diseases. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example, next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Elucidating the role of stem cell⁻host microbiome cross talks in tissues in GBA disorders might lead to the development of next generation diagnostics and therapeutics. Psychobiotics are a new class of beneficial bacteria with documented efficacy for the treatment of GBA disorders. Novel therapies interfering with small molecules involved in adult stem cell trafficking are on the horizon.