Dynamics of the Gut Microbiota and Faecal and Serum Metabolomes during Pregnancy-A Longitudinal Study.

Normal pregnancy involves numerous physiological changes, including changes in hormone levels, immune responses, and metabolism. Although several studies have shown that the gut microbiota may have an important role in the progression of pregnancy, these findings have been inconsistent, and the relationship between the gut microbiota and metabolites that change dynamically during and after pregnancy remains to be clarified. In this longitudinal study, we comprehensively profiled the temporal dynamics of the gut microbiota, Bifidobacterium communities, and serum and faecal metabolomes of 31 women during their pregnancies and postpartum periods. The microbial composition changed as gestation progressed, with the pregnancy and postpartum periods exhibiting distinct bacterial community characteristics, including significant alterations in the genera of the Lachnospiraceae or Ruminococcaceae families, especially the Lachnospiraceae FCS020 group and Ruminococcaceae UCG-003. Metabolic dynamics, characterised by changes in nutrients important for fetal growth (e.g., docosatrienoic acid), anti-inflammatory metabolites (e.g., trans-3-indoleacrylic acid), and steroid hormones (e.g., progesterone), were observed in both serum and faecal samples during pregnancy. Moreover, a complex correlation was identified between the pregnancy-related microbiota and metabolites, with Ruminococcus1 and Ruminococcaceae UCG-013 making important contributions to changes in faecal and serum metabolites, respectively. Overall, a highly coordinated microbiota-metabolite regulatory network may underlie the pregnancy process. These findings provide a foundation for enhancing our understanding of the molecular processes occurring during the progression of pregnancy, thereby contributing to nutrition and health management during this period.

Streptococcus salivarius subsp. thermophilus CCFM1312 enhanced mice resilience to activity-based anorexia.

Probiotic intervention, already showing promise in the treatment of various psychiatric disorders like depression, emerges as a potential therapy for anorexia nervosa (AN) with minimal side effects. In this study, we established an activity-based anorexia (ABA) model to probe the pathogenesis of AN and assess the impact of probiotics on ABA mice. ABA resulted in a compensatory increase in duodenal ghrelin levels, impairing the regulation of feeding and the brain reward system. Intervention with Streptococcus salivarius subsp. thermophilus CCFM1312 ameliorated these ABA-induced effects, and the activation of neurons in the nucleus tractus solitarius (NTS) was observed following probiotic administration, revealing the advantageous role of probiotics in AN through the vagus nerve. Furthermore, our metabolomics analysis of cecal contents unveiled that S. salivarius subsp. thermophilus CCFM1312 modulated gut microbiota metabolism and thereby regulated intestinal ghrelin levels.

Determining the emotional regulation function of Bifidobacterium breve: the role of gut metabolite regulation over colonization capability.

Psychobiotics that modulate the gut-brain axis have emerged as promising interventions for clinical mental disorders. Bifidobacterium breve CCFM1025 has demonstrated antidepressant effects in both mice and patients with major depression. Nevertheless, the precise mechanism of action of CCFM1025 in emotional regulation remains ambiguous. This study aimed to explore the colonization capacity of CCFM1025 and its dose-dependent effect on emotional regulation in mice exposed to chronic unpredictable mild stress (CUMS). Additionally, we examined its regulatory effects on intestinal and serum metabolites in mice. The results revealed that CCFM1025 did not exhibit a heightened gut retention capability compared to the conspecific control strain. Nevertheless, CCFM1025 exhibited dose-dependent mitigation of anxiety-like behavior and memory impairment induced by CUMS, while also restoring gut microbiota homeostasis. Notably, CCFM1025 demonstrated a robust ability to exert potent gut metabolite regulation, resulting in significant elevation of bile acid and tryptophan metabolites in the gut contents and serum of mice. These findings indicate that the impact of CCFM1025 on emotional regulation may be attributed to its regulation of gut metabolites rather than its gut retention capability. The potential of Bifidobacterium to modulate bile acid metabolism may serve as a valuable avenue for regulating the gut microbiota and successfully exert emotion regulation.

Psychobiotics Regulate Purine Metabolism to Influence Host Emotional Behavior.

Purine metabolism plays a pivotal role in numerous biological processes with potential implications for brain function and emotional regulation. This study utilizes gene-edited probiotics and pseudo-germ-free mice to unravel this intricate interplay. Transcriptomic analysis identified a ribonucleoside-diphosphate reductase ß chain (nrdB) as a pivotal gene in purine metabolism within Bifidobacterium breve CCFM1025. Comparative evaluation between the wild-type and nrdB mutant strains revealed CCFM1025's effective reduction of xanthine and xanthosine levels in the serum and brain of stressed mice. Concomitantly, it downregulated the expression of the adenosine receptor gene (Adora2b) and inhibited the overactivation of microglia. These findings emphasize the potential of psychobiotics in modulating emotional responses by regulating purine metabolites and adenosine receptors. This study sheds light on novel pathways that influence emotional well-being through gut microbiota interactions and purine metabolic processes.

Bifidobacterium breve CCFM1025 Improves Sleep Quality via Regulating the Activity of the HPA Axis: A Randomized Clinical Trial.

Psychobiotics, a newly identified category of probiotics primarily targeting the gut-brain axis, exhibit tremendous potential in improving sleep quality. In this study, the clinical trial was registered in advance (identifier: NO. ChiCTR2300067806). Forty participants who were diagnosed with stress-induced insomnia were chosen and randomly divided into two groups: one received CCFM1025 at a dose of 5 × 109 CFU (n = 20), while the other was administered a placebo (n = 20), over a period of four weeks. The results revealed that compared to the placebo group (pre: M = 10.10, SD = 2.292; post: M = 8.650, SD = 2.793; pre vs. post: F (1, 38) = 15.41, p = 0.4316), the CCFM1025-treated group exhibited a significant decrease in Pittsburgh Sleep Quality Index (PSQI) scores from baseline (pre: M = 11.60, SD = 3.169; post: M = 7.750, SD = 3.697, F (1, 38) = 15.41, p = 0.0007). Furthermore, the administration of CCFM1025 was associated with a more pronounced reduction in stress marker concentrations. This effect could potentially be linked to changes in serum metabolites induced by the probiotic treatment, notably daidzein. In conclusion, B. breve CCFM1025 demonstrates promise as a psychobiotic strain for enhancing sleep quality.

Dietary Nucleotides Promote Neonatal Rat Microbiota-Gut-Brain Axis Development by Affecting Gut Microbiota Composition and Metabolic Function.

A variety of active factors in milk and foods have been proven to serve as microbial nutrients that regulate the formation of early gut microbiota (GM), thereby ensuring the healthy development of infants. This study demonstrated that dietary nucleotides (NTs), one of the main nitrogen-containing substances in human milk, promoted the neurodevelopment of neonatal rats and the expression of Sox2, Dcx, Tuj1, and NeuN in the prefrontal cortex and hippocampus, but had no significant regulatory effects in the striatum. 16s rRNA sequencing and metabolomics of the colon contents of neonatal rats at different developmental stages showed that the early intake of NTs promoted an increase in the abundance of beneficial microorganisms related to neurodevelopment, digestion, and gut absorption, such as g_Romboutsia and g_Akkermansia. Changes in the ability of the GM to regulate folate synthesis, riboflavin metabolism, and other processes were also observed. Further analysis revealed significant correlations between the level of characteristic metabolites, namely, trans-3-indoleacrylic acid, urocanic acid, inosine, and adenosine, in the gut with neurodevelopment and characteristic GM components. These findings suggest that NTs in milk may affect neurodevelopment and maturation in early life by regulating the GM composition-gut-brain axis.

Colon-Targeted Delivery of Indole Acetic Acid Helps Regulate Gut Motility by Activating the AHR Signaling Pathway.

Intestinal peristalsis is vital for gastrointestinal physiology and host homeostasis and is frequently dysregulated in intestinal disorders. Gut microbiota can regulate gut motility, especially through the tryptophan metabolism pathway. However, the role of indoles as microbial tryptophan metabolites in colonic function requires further exploration. Here, we show that the delivery of indole acetic acid (IAA) targeting the colon can improve gut motility by activating the aryl hydrocarbon receptor (AHR). To achieve colon-targeted delivery, Eudragit S-100 (ES) and chitosan (CS) were used as drug carriers. After optimisation, IAA-loaded ES-coated CS nanoparticles exhibited an encapsulation efficiency of 83% and a drug-loading capacity of 16%. These nanoparticles exhibited pH-dependent characteristics and remained stable in acidic conditions and the upper intestine. In simulated intestinal fluid (pH 7.4) and colonic lumen, considerable amounts of IAA were released after approximately 4 h. Compared with free IAA, the nanoparticles exerted enhanced therapeutic effects on gut movement disorders induced by loperamide. The efficacy of IAA treatment was attributable to the activation of the AHR signalling pathway and increased levels of AHR agonists. Furthermore, the oral administration of IAA-loaded nanoparticles promoted serotonin secretion and maintained the intestinal barrier function. The experimental outcomes demonstrate the efficiency of the proposed colon-specific delivery system and highlight the role of IAA, produced by gut microbiota metabolism, in regulating gut peristalsis through AHR activation.

Uncovering Predictive Factors and Interventions for Restoring Microecological Diversity after Antibiotic Disturbance.

Antibiotic treatment can lead to a loss of diversity of gut microbiota and may adversely affect gut microbiota composition and host health. Previous studies have indicated that the recovery of gut microbes from antibiotic-induced disruption may be guided by specific microbial species. We expect to predict recovery or non-recovery using these crucial species or other indices after antibiotic treatment only when the gut microbiota changes. This study focused on this prediction problem using a novel ensemble learning framework to identify a set of common and reasonably predictive recovery-associated bacterial species (p-RABs), enabling us to predict the host microbiome recovery status under broad-spectrum antibiotic treatment. Our findings also propose other predictive indicators, suggesting that higher taxonomic and functional diversity may correlate with an increased likelihood of successful recovery. Furthermore, to explore the validity of p-RABs, we performed a metabolic support analysis and identified Akkermansia muciniphila and Bacteroides uniformis as potential key supporting species for reconstruction interventions. Experimental results from a C57BL/6J male mouse model demonstrated the effectiveness of p-RABs in facilitating intestinal microbial reconstitution. Thus, we proved the reliability of the new p-RABs and validated a practical intervention scheme for gut microbiota reconstruction under antibiotic disturbance.

Statistical modeling of gut microbiota for personalized health status monitoring.

BACKGROUND: The gut microbiome is closely associated with health status, and any microbiota dysbiosis could considerably impact the host's health. In addition, many active consortium projects have generated many reference datasets available for large-scale retrospective research. However, a comprehensive monitoring framework that analyzes health status and quantitatively present bacteria-to-health contribution has not been thoroughly investigated. METHODS: We systematically developed a statistical monitoring diagram for personalized health status prediction and analysis. Our framework comprises three elements: (1) a statistical monitoring model was established, the health index was constructed, and the health boundary was defined; (2) healthy patterns were identified among healthy people and analyzed using contrast learning; (3) the contribution of each bacterium to the health index of the diseased population was analyzed. Furthermore, we investigated disease proximity using the contribution spectrum and discovered multiple multi-disease-related targets. RESULTS: We demonstrated and evaluated the effectiveness of the proposed monitoring framework for tracking personalized health status through comprehensive real-data analysis using the multi-study cohort and another validation cohort. A statistical monitoring model was developed based on 92 microbial taxa. In both the discovery and validation sets, our approach achieved balanced accuracies of 0.7132 and 0.7026, and AUC of 0.80 and 0.76, respectively. Four health patterns were identified in healthy populations, highlighting variations in species composition and metabolic function across these patterns. Furthermore, a reasonable correlation was found between the proposed health index and host physiological indicators, diversity, and functional redundancy. The health index significantly correlated with Shannon diversity ([Formula: see text]) and species richness ([Formula: see text]) in the healthy samples. However, in samples from individuals with diseases, the health index significantly correlated with age ([Formula: see text]), species richness ([Formula: see text]), and functional redundancy ([Formula: see text]). Personalized diagnosis is achieved by analyzing the contribution of each bacterium to the health index. We identified high-contribution species shared across multiple diseases by analyzing the contribution spectrum of these diseases. CONCLUSIONS: Our research revealed that the proposed monitoring framework could promote a deep understanding of healthy microbiomes and unhealthy variations and served as a bridge toward individualized therapy target discovery and precise modulation. Video Abstract.

The Effect of Probiotic Supplementation on Glucolipid Metabolism in Patients with Type 2 Diabetes: A Systematic Review and Meta-Analysis.

PURPOSE: Type 2 diabetes mellitus (T2DM) is a persistent metabolic condition with an unknown pathophysiology. Moreover, T2DM remains a serious health risk despite advances in medication and preventive care. Randomised controlled trials (RCTs) have provided evidence that probiotics may have positive effects on glucolipid metabolism. Therefore, we performed a meta-analysis of RCTs to measure the effect of probiotic therapy on glucolipid metabolism in patients with T2DM. METHODS: With no constraints on the language used in the literature, Excerpta Medica Database, PubMed, the Cochrane Library, and the Web of Science were searched for pertinent RCTs published between the date of creation and 18 August 2022. Stringent inclusion and exclusion criteria were applied by two reviewers to independently examine the literature. The risk of bias associated with the inclusion of the original studies was assessed using the Cochrane risk-of-bias tool, and Stata 15.0 was used to perform the meta-analysis. RESULTS: Thirty-seven publications containing a total of 2502 research participants were included in the meta-analysis. The results showed that after a probiotic intervention, the experimental group showed a significant decrease in body mass index (standardised mean difference (SMD) = -0.42, 95% confidence interval (CI) [-0.76, -0.08]), fasting glucose concentration (SMD = -0.73, 95% CI [-0.97, -0.48]), fasting insulin concentration (SMD = -0.67, 95% CI [-0.99, -0.36]), glycated haemoglobin concentration (SMD = -0.55, 95% CI [-0.75, -0.35]), Homeostatic Model Assessment for Insulin Resistance score (SMD = -0.88, 95% CI [-1.17, -0.59]), triglyceride concentration (SMD = -0.30, 95% CI [-0.43, -0.17]), total cholesterol concentration (SMD = -0.27, 95% CI [-0.43, -0.11]), and low-density lipoprotein concentration (SMD = -0.20, 95% CI [-0.37, -0.04]), and an increase in high-density lipoprotein concentration (SMD = 0.31, 95% CI [0.08, 0.54]). Moreover, subgroup analyses showed that patients with a longer intervention time, or those who were treated with multiple strains of probiotics, may benefit more than those with a shorter intervention time or those who were treated with a single probiotic strain, respectively. CONCLUSION: Probiotic supplementation improves glucolipid metabolism in patients with T2DM, offering an alternative approach for the treatment of these patients.

Detection of colonization capacity of probiotic Bifidobacterium breve CCFM1025 in the human gut.

Aim: To detect the gut colonization capacity of Bifidobacterium breve CCFM1025 with clinical antidepressant-like effects. Materials & methods: A unique gene sequence of B. breve CCFM1025 was discovered based on the genome analysis of 104 B. breve strains and a strain-specific primer (1025T5) was designed. In vitro and in vivo samples were used to validate the specificity and quantitative capability of this primer in the PCR system. Results: Quantitative PCR using strain-specific primers enabled absolute quantification of CCFM1025 in fecal samples within 104-1010 cells/g (R2 >0.99). CCFM1025 remained highly detectable in volunteer feces 14 days after cessation of administration, demonstrating its favorable colonization characteristics. Conclusion: CCFM1025 can colonize the healthy human gut.

Multi-Probiotics ameliorate Major depressive disorder and accompanying gastrointestinal syndromes via serotonergic system regulation.

INTRODUCTION: Major depressive disorder (MDD) is a leading global psychiatric disease. MDD is highly comorbid with gastrointestinal abnormalities, such as gut motility dysfunction. An effective strategy to manage depression and its accompanying gastrointestinal symptoms is warranted. OBJECTIVES: Three probiotic strains (Bifidobacterium breve CCFM1025, Bifidobacterium longum CCFM687, and Pediococcus acidilactici CCFM6432) had previously been validated in mice to possess antidepressant-like potential. This study investigated the potential psychotropic effects of a combined three-strain probiotic intervention for human MDD patients. The mechanism of action was further investigated in the stress-induced depression mice model. METHODS: MDD patients were given a freeze-dried, mixed probiotic formula for four weeks. The patients' psychometric and gastrointestinal conditions were evaluated using clinical rating scales before and after treatment. Their gut microbiome was also analysed using 16S rRNA gene amplicon sequencing. The mechanisms underlying the beneficial probiotic effects were determined using a chronic stress-induced depressive mouse model. RESULTS: Multi-probiotics significantly reduced depression scores, and to a greater extent than the placebo (based on the Hamilton Depression Rating, Montgomery-Asberg Depression Rating, and Brief Psychiatric Rating Scales). Multi-probiotics also significantly improved the patients' gastrointestinal functions (based on self-evaluation using the Gastrointestinal Symptom Rating Scale). Serotonergic system modification was demonstrated as the key mechanism behind the probiotics' benefits for the brain and the gut. CONCLUSION: Our findings suggest a novel and promising treatment to manage MDD and accompanying gut motility problems, and provide options for treating other gut-brain axis-related disorders.

Gut microbiome-brain interactions in anorexia nervosa: Potential mechanisms and regulatory strategies.

Anorexia nervosa (AN) is a psychiatric disorder characterised by malnutrition, fear of weight gain, and body image disturbances. The aetiology of AN is complex, and may involve environmental factors, genetic factors, and biochemical factors, with the latter meaning that AN may be closely associated with neurons, neurotransmitters, and hormones related to appetite and emotional regulation. In addition, an increasing number of studies have shown there is a link between the intestinal microbiota and psychiatric disorders, such as depression. However, few studies and reviews have focused on AN and gut microbes. Accordingly, in this review, we examine the potential pathogenesis of AN in terms of changes in the gut microbiota and its metabolites, and their effects on AN. The neurobiological function of the nervous system in relation to AN are also been mentioned. Furthermore, we suggest future research directions for this field, and note that probiotics may be developed for use as dietary supplements to help alleviate AN in patients.

Indole Acetic Acid Exerts Anti-Depressive Effects on an Animal Model of Chronic Mild Stress.

Indole acetic acid (IAA), an intestinal bacteria-derived tryptophan metabolite, has been detected at abnormal concentrations in the cerebrospinal fluid and urine of depressed individuals. The effects of such altered IAA concentrations on mood regulation are not known. A mouse model of unpredictable chronic mild stress (UCMS) was used to assess the effects of IAA administration (50 mg/kg). Treatment with IAA for 5 weeks attenuated depression and anxiety-like behaviours, improved hypothalamus-pituitary-adrenal axis dysfunction and increased brain-derived neurotrophic factor expression. IAA supplementation also enhanced the serotonin pathway in the brain and gut. UCMS caused an imbalance of microbial indole metabolites in the colon, whereas IAA treatment reversed this. However, IAA intake did not affect the concentrations of indoles in the brain. Intestinal bacteria in different sections of the gut were altered by IAA treatment, with the colon showing more changes than other segments. The gut microbiome in the colon had increased proportions of Ruminococcaceae UCG013, Ruminiclostridium 6, Prevotella, Alloprevotella and Bacteroides species, which can produce short-chain fatty acids and indole derivatives. Cumulatively, our study highlights the potential of IAA treatment to alleviate mood disorders and offers a theoretical basis for understanding the antidepressant effects of IAA.

Perinatal transmission of a probiotic Bifidobacterium strain protects against early life stress-induced mood and gastrointestinal motility disorders.

Early life stress can considerably interfere in gut microbiome formation and nervous system development. Specific probiotic strains have been proved to exert anti-stress effects by modulating the gut-brain axis. However, little is known about whether probiotic treatment during pregnancy can protect the offspring from early life stress. In this study, Bifidobacterium breve CCFM1025, previously proven to exert microbial and neurobiological regulation effects, was given to pregnant mice. The offspring's gut and brain functions were evaluated when challenged with maternal separation. Intriguingly, treatment with probiotics during pregnancy protected the offspring from maternal separation-induced neurobiological and gastrointestinal disorders such as depression-like behaviour and delayed defecation. Quantification of CCFM1025 was performed, and perinatal transmission of CCFM1025 was further validated, which also explained the reason for increased levels of colonic 5-hydroxytryptamine and caecal short-chain fatty acids in the offspring. Our findings indicated that the effects of probiotics can be perinatally transmitted through gut microbes and that probiotic treatment during pregnancy may have great potential in managing health risks in early life.

Fecal microbiota transplantation for diseases: Therapeutic potential, methodology, risk management in clinical practice.

BACKGROUND: More than 95 % of human diseases may be related to the disturbance of gut microbes. As a treatment method that extensively regulates the gut microbes, fecal microbiota transplantation (FMT) has proven to be an effective therapy for some diseases, becoming a topic of interest among clinicians, patients and scientists. AIM: To review the latest clinical research results of FMT in the treatment of various diseases and the methodology and risk management in clinical application. METHODS: Search PubMed and Web of Science for reliable research results of clinical treatment of FMT within 5-10 years, as well as application guidelines and risk management policies in different regions. RESULTS: As a measure of allogeneic/autologous microbiota transplantation, FMT has been used to treat a variety of diseases. By reviewing the clinical studies of FMT in gastrointestinal diseases, metabolic diseases, neurological diseases and malignant tumors, the various mechanisms in the treatment of diseases are summarized. Such as regulation of receptor microbiota composition, specific metabolites, phage function and immune response. In addition, potential risk factors, donor stool screening indicators, recipient self-specificity and possible prognostic marker molecules in the course of FMT treatment were generalized. CONCLUSIONS: The potential regulatory mechanisms, risk factors and targets of FMT in gastrointestinal diseases, metabolic diseases, malignancies and neurological diseases were reviewed and proposed. It provides a theoretical basis for the establishment of a standardized treatment system for FMT and a breakthrough in treatment technology.

Lactic acid bacteria alleviate di-(2-ethylhexyl) phthalate-induced liver and testis toxicity via their bio-binding capacity, antioxidant capacity and regulation of the gut microbiota.

Di-(2-ethylhexyl) phthalate (DEHP) is a plasticiser that, if absorbed into the human body, can cause various adverse effects including reproductive toxicity, liver toxicity and gut microbiota dysbiosis. So far, some studies have proved that the toxicity of DEHP can be reduced by using antioxidants. However, these candidates all show potential side effects and cannot prevent the accumulation of DEHP in the body, making them unable to be used as a daily dietary supplement to relieve the toxic effects of DEHP. Lactic acid bacteria (LAB) have antioxidant capacity and the ability to adsorb harmful substances. Herein, we investigated the protective effects of five strains of LAB, selected based on our in vitro assessments on antioxidant capacities or bio-binding capacities, against the adverse effects of DEHP exposure in rats. Our results showed that LAB strains with outstanding DEHP/MEHP binding capacities, Lactococcus lactis subsp. lactis CCFM1018 and Lactobacillus plantarum CCFM1019, possess the ability to facilitate the elimination of DEHP and its metabolite mono-(2-ethylhexyl) phthalate (MEHP) with the faeces, decrease DEHP and MEHP level in serum further. Meanwhile, DEHP-induced liver and testicular injuries were effectively alleviated by CCFM1018 and CCFM1019. In addition, CCFM1018 effectively alleviated the DEHP-induced oxidative stress with its strong antioxidant ability. Furthermore, both CCFM1018 and CCFM1019 modulated the gut microbiota, which in turn increased the concentrations of faecal propionate and butyrate and regulated the pathways related to host metabolism. Correlation analysis indicate that DEHP/MEHP bio-binding capacity of LAB plays a crucial role in protecting the body from DEHP exposure, and its antioxidant capacity and the ability to alleviate the gut microbiota dysbiosis are also involved in the alleviation of damage. Thus, LAB with powerful bio-binding capacity of DEHP and MEHP can be considered as a potential therapeutic dietary strategy against DEHP exposure.

Lactobacillus paracasei CCFM1229 and Lactobacillus rhamnosus CCFM1228 Alleviated Depression- and Anxiety-Related Symptoms of Chronic Stress-Induced Depression in Mice by Regulating Xanthine Oxidase Activity in the Brain.

Depression is a common mood disorder that affects around 350 million people worldwide. We studied the effect of supplementation with Lactobacillus strains for the treatment of depression. Except for control group (n = 8), C57BL/6J mice were treated with Lactobacillus during six weeks of chronic unpredictable stress (depression group: n = 9, Lactobacillus intervention group: n = 7). L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly reduced depressive behaviour in the forced swimming test and tail suspension test, significantly reduced anxiety behaviour in the open field test, and reduced anxiety behaviour in the marble burying test and light/dark box test. L. paracasei CCFM1229 and L. rhamnosus CCFM1228 significantly increased the brain serotonin and brain-derived neurotrophic factor concentrations, and CCFM1229 significantly decreased the serum corticosterone concentration, all of which are closely associated with the relief of depressive symptoms. Furthermore, CCFM1229 and CCFM1228 were shown to regulate purine metabolism in mice, as indicated by decreases in brain xanthine oxidase activity and an increase in liver adenosine deaminase activity. Anxiety- and depression-related indicators were significantly associated with xanthine oxidase activity in the cerebral cortex. The strains CCFM1229 and CCFM1228 reduced anxiety- and depression-related behaviour in a mouse model of chronic stress-induced depression, which may be achieved by regulating the activity of brain xanthine oxidase.

A randomised, double-blind, placebo-controlled trial of Bifidobacterium bifidum CCFM16 for manipulation of the gut microbiota and relief from chronic constipation.

A variety of opinions exist on the potential of probiotics to provide relief from chronic constipation with much focus being placed on their mechanism of action and causes of heterogeneity in the results of different studies. We aimed to determine the efficacy and safety of ingesting Bifidobacterium bifidum (B. bifidum) CCFM16 for 28 days to relieve constipation and to understand the mechanism of action. Using Rome IV criterion, 53 and 50 participants diagnosed with chronic constipation were included in the probiotic group and placebo group, respectively. Spontaneous bowel movements (SBMs) per week, stool consistency (Bristol Stool Form Scale [BSFS]), the proportion of SBM responders, patient assessment of constipation symptoms (PAC-SYM), and quality of life (PAC-QoL) were evaluated. The gut microbiota, short-chain fatty acids (SCFAs) and other indicators were also assessed. B. bifidum CCFM16 treatment improved the stool consistency and increased the proportion of SBM responders, but the differences in PAC-SYM and PAC-QoL were statistically insignificant between the groups. Analysis of the SCFAs and microbiome revealed that CCFM16 significantly increased the acetic acid and butyric acid concentrations and enhanced the Firmicutes/Bacteroidetes ratio. Levels of Clostridia were particularly increased and were associated with the increase in butyric acid. In addition, we found the other side of Clostridia; several taxa in the order Clostridiales were observed to prevent CCFM16 from proper functioning in the pre-treatment microbiome. In conclusion, CCFM16 can potentially and efficaciously relieve chronic constipation in Chinese adults by regulating the gut microbiota and SCFA metabolism. The two sides of Clostridia illustrate its importance in microbial therapy for constipation.

Bifidobacterium breve CCFM1025 attenuates major depression disorder via regulating gut microbiome and tryptophan metabolism: A randomized clinical trial.

OBJECTIVE: Psychobiotics, as a novel class of probiotics mainly acting on the gut-brain axis, have shown promising prospects in treating psychiatric disorders. Bifidobacterium breve CCFM1025 was validated to have an antidepressant-like effect in mice. This study aims to assess its psychotropic potential in managing major depression disorder (MDD) and unravel the underlying mechanisms. METHODS: Clinical Trial Registration: https://www.chictr.org.cn/index.aspx (identifier: NO. ChiCTR2100046321). Patients (n = 45) diagnosed with MDD were randomly assigned to the Placebo (n = 25) and CCFM1025 (n = 20) groups. The freeze-dried CCFM1025 in a dose of viable bacteria of 1010 CFU was given to MDD patients daily for four weeks, while the placebo group was given maltodextrin. Changes from baseline in psychometric and gastrointestinal symptoms were evaluated using Hamilton Depression Rating scale-24 Items (HDRS-24), Montgomery-Asberg Depression Rating Scale (MADRS), Brief Psychiatric Rating Scale (BPRS), and Gastrointestinal Symptom Rating Scale (GSRS). Serum measures were also determined, i.e., cortisol, TNF-α, and IL-ß. Serotonin turnover in the circulation, gut microbiome composition, and tryptophan metabolites were further investigated for clarifying the probiotics' mechanisms of action. RESULTS: CCFM1025 showed a better antidepressant-like effect than placebo, based on the HDRS-24 (placebo: M = 6.44, SD = 5.44; CCFM1025: M = 10.40, SD = 6.85; t(43) = 2.163, P = 0.036, d = 0.640) and MADRS (placebo: M = 4.92, SD = 7.15; CCFM1025: M = 9.60, SD = 7.37; t(43) = 2.152, P = 0.037, d = 0.645) evaluation. The factor analysis of BPRS and GSRS suggested that patients' emotional and gastrointestinal problems may be affected by the serotonergic system. Specifically, CCFM1025 could significantly and to a larger extend reduce the serum serotonin turnover compared with the placebo (placebo: M = -0.01, SD = 0.41; CCFM1025: M = 0.27, SD = 0.40; t(43) = 2.267, P = 0.029, d = 0.681). It may be due to changes in gut microbiome and gut tryptophan metabolism under the probiotic treatment, such as changes in alpha diversity, tryptophan, and indoles derivatives. CONCLUSION: B. breve CCFM1025 is a promising candidate psychobiotic strain that attenuates depression and associated gastrointestinal disorders. The mechanisms may be relevant to the changes in the gut microbiome and tryptophan metabolism. These findings support the future clinical applications of psychobiotics in the treatment of psychiatric disorders.