Gut microbially produced tryptophan metabolite melatonin ameliorates osteoporosis via modulating SCFA and TMAO metabolism.

Osteoporosis (OP) is a severe global health issue that has significant implications for productivity and human lifespan. Gut microbiota dysbiosis has been demonstrated to be closely associated with OP progression. Melatonin (MLT) is an important endogenous hormone that modulates bone metabolism, maintains bone homeostasis, and improves OP progression. Multiple studies indicated that MLT participates in the regulation of intestinal microbiota and gut barrier function. However, the promising effects of gut microbiota-derived MLT in OP remain unclear. Here, we found that OP resulted in intestinal tryptophan disorder and decreased the production of gut microbiota-derived MLT, while administration with MLT could mitigate OP-related clinical symptoms and reverse gut microbiota dysbiosis, including the diversity of intestinal microbiota, the relative abundance of many probiotics such as Allobaculum and Parasutterella, and metabolic function of intestinal flora such as amino acid metabolism, nucleotide metabolism, and energy metabolism. Notably, MLT significantly increased the production of short-chain fatty acids and decreased trimethylamine N-oxide-related metabolites. Importantly, MLT could modulate the dynamic balance of M1/M2 macrophages, reduce the serum levels of pro-inflammatory cytokines, and restore gut-barrier function. Taken together, our results highlighted the important roles of gut microbially derived MLT in OP progression via the "gut-bone" axis associated with SCFA metabolism, which may provide novel insight into the development of MLT as a promising drug for treating OP.

Citrus pectin protects mice from burn injury by modulating intestinal microbiota, GLP-1 secretion and immune response.

Water-soluble rhamnogalacturonan-I enriched citrus pectin (WRP) has promising effect on antimicrobial defense. We aim to determine whether the modified acidic (A) or neutral (B) WRP solutions can improve intestinal microbial dysbiosis in burn-injured mice. Male Balb/c mice were gavaged with WRPs at 80, 160, 320 mg/kg. Body weight daily for 21 days before exposed to thermal injury of 15 % total body surface area and mortality was monitored. Mice with 80 mg/kg WRPs were also subjected to fecal DNAs and T cell metabonomics analysis, intestinal and plasma glucagon-like peptide 1 (GLP-1) detection, plasma defensin, immunoglobin and intestinal barrier examinations at 1 and 3d postburn (p.b.). Burn-induced mortality was only improved by low dose WRP-A (P = 0.039). Both WRPs could prevent the dysbiosis of gut microbiota in burn injury by reducing the expansion of inflammation-promoting bacteria. Both WRPs suppressed ileum GLP-1 production at 1d p.b. (P = 0.002) and plasma GLP-1 levels at 3d p.b. (P = 0.013). Plasma GLP-1 level correlated closely with ileum GLP-1 production (P = 0.019) but negatively with microbiota diversity at 1d p.b. (P = 0.003). Intestinal T cell number was increased by both WRPs in jejunum at 3d p.b. However, the exaggerated splenic T cell metabolism in burn injury was reversed by both WRPs at 1d p.b. The burn-increased plasma defensin ß1 level was only reduced by WRP-B. Similarly, the intestinal barrier permeability was only rescued by WRP-B at 1d p.b. WRP-A rather than WRP-B could reduce burn-induced mortality in mice by suppressing intestinal GLP-1 secretion, restoring gut microbiota dysbiosis and improving adaptive immune response.

Psychobiotics Lactiplantibacillus plantarum JYLP-326: Antidepressant-like effects on CUMS-induced depressed mouse model and alleviation of gut microbiota dysbiosis.

BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.

Large Yellow Tea Polysaccharide Alleviates HFD-Induced Intestinal Homeostasis Dysbiosis via Modulating Gut Barrier Integrity, Immune Responses, and the Gut Microbiome.

Long-term high-fat diet (HFD) will induce dysbiosis and a disturbance of intestinal homeostasis. Large yellow tea polysaccharide (LYP) has been shown to improve obesity-associated metabolic disease via modulation of the M2 polarization. However, the contribution of LYP to intestinal barrier impairment and improvement mechanisms in obesity caused by an HFD are still not clear. In this study, we evaluated the impacts of LYP on the mucosal barrier function and microbiota composition in HFD-feeding mice. Results exhibited that dietary LYP supplement could ameliorate the physical barrier function via maintaining intestinal mucosal integrity and elevating tight-junction protein production, strengthen the chemical barrier function via up-regulating the levels of glucagon-like peptide-1 and increasing mucin-producing goblet cell numbers, and enhance the intestinal immune barrier function though suppressing immune cell subsets and cytokines toward pro-inflammatory phenotypes. Moreover, LYP reshaped the constitution and metabolism of intestinal flora by enriching probiotics that produce short-chain fatty acids. Overall, LYP might be used as a critical regulator of intestinal homeostasis to improve host health by promoting gut barrier integrity, modulating intestinal immune response, and inhibiting bowel inflammation.

Role of Inflammatory Mechanisms in Major Depressive Disorder: From Etiology to Potential Pharmacological Targets.

The involvement of central and peripheral inflammation in the pathogenesis and prognosis of major depressive disorder (MDD) has been demonstrated. The increase of pro-inflammatory cytokines (interleukin (IL)-1ß, IL-6, IL-18, and TNF-α) in individuals with depression may elicit neuroinflammatory processes and peripheral inflammation, mechanisms that, in turn, can contribute to gut microbiota dysbiosis. Together, neuroinflammation and gut dysbiosis induce alterations in tryptophan metabolism, culminating in decreased serotonin synthesis, impairments in neuroplasticity-related mechanisms, and glutamate-mediated excitotoxicity. This review aims to highlight the inflammatory mechanisms (neuroinflammation, peripheral inflammation, and gut dysbiosis) involved in the pathophysiology of MDD and to explore novel anti-inflammatory therapeutic approaches for this psychiatric disturbance. Several lines of evidence have indicated that in addition to antidepressants, physical exercise, probiotics, and nutraceuticals (agmatine, ascorbic acid, and vitamin D) possess anti-inflammatory effects that may contribute to their antidepressant properties. Further studies are necessary to explore the therapeutic benefits of these alternative therapies for MDD.

The Role of Probiotics in the Prevention of Clostridioides difficile Infection in Patients with Chronic Kidney Disease.

In patients suffering from chronic kidney disease (CKD), substantial unfavourable alterations in the intestinal microbiota composition, i.e., dysbiosis, have been noted. The main causes of such dysbiosis among others are insufficient dietary fibre content in the diet, fluid restrictions, medications used, and physical activity limitation. One clinically important consequence of dysbiosis in CKD patients is high risk of Clostridioides difficile infection (CDI). In observational studies, it was found that CDI is more frequent in CKD patients than in the general population. This appears to be related to high hospitalization rate and more often antibiotic therapy use, leading up to the occurrence of dysbiosis. Therefore, the use of probiotics in CKD patients may avert changes in the intestinal microbiota, which is the major risk factor of CDI. The aim of this review paper is to summarize the actual knowledge concerning the use of probiotics in CDI prevention in CKD patients in the context of CDI prevention in the general population.

Ethanol extracts of Isochrysis zhanjiangensis alleviate acute alcoholic liver injury and modulate intestinal bacteria dysbiosis in mice.

BACKGROUND: Alcoholic liver disease (ALD) is responsible for 3.3 million deaths per annum. Efficacious therapeutic modalities or drug treatments for ALD have not yet been found, so it is urgent to seek new agents for preventing ALD and its related disease. Many experiments have indicated that modulating the gut microbiota and regulating the toll-like receptor 4 (TLR4)/nuclear transcription factor-κB (NF-κB) inflammatory pathway can provide a new target for prevention and treatment of ALD. Marine microalgae have their natural metabolic pathways to synthesize various of bioactive compounds as promising candidates for hepatoprotection. In this study, we investigated ethanol extracts from Isochrysis zhanjiangensis (EEIZ) to evaluate their ability to alleviate acute alcoholic liver injury, regulate TLR4/NF-κB inflammatory pathway and modulate intestinal bacteria dysbiosis in mice for ALD treatment. RESULTS: In the acute ALD mouse model, EEIZ reduced levels of aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, triacylglyceride, total cholesterol and low-density lipoprotein, while increasing the level of high-density lipoprotein. Besides, TLR4, myeloid differentiation factor 88, NF-κB and tumor necrosis factor-α expression levels in liver tissue were effectively downregulated by EEIZ. Furthermore, treatment with EEIZ enhanced intestinal homeostasis and significantly alleviated the damage caused by alcohol. CONCLUSION: EEIZ showed effective hepatoprotective activity against alcohol-induced acute liver injury in mice as it could alleviate hepatocyte damage, suppress the TLR4/NF-κB inflammatory pathway and regulate the intestinal flora structure. EEIZ could be a good candidate for preventing acute alcoholic liver injury. © 2024 Society of Chemical Industry.

Fucoxanthin Alleviates Dextran Sulfate Sodium-Induced Colitis and Gut Microbiota Dysbiosis in Mice.

The purpose of this study was to evaluate the preventive role and underlying mechanisms of fucoxanthin (Fx) on dextran sulfate sodium (DSS)-induced colitis in mice. The present data demonstrated that oral administration of Fx (50 and 200 mg/kg body weight/day) for 36 days significantly alleviated the severity of colitis in DSS-treated mice, as evidenced by attenuating body weight loss, bloody stool, diarrhea, shortened colon length, colonic epithelium distortion, a thin mucus layer, goblet cell depletion, damaged crypts, and extensive infiltration of inflammatory cells in the colonic mucosa. Additionally, Fx notably relieved DSS-induced intestinal epithelial barrier dysfunction via maintaining the tight junction function and preventing excessive apoptosis of colonic epithelial cells. Moreover, Fx effectively diminished colonic inflammation and oxidative stress in DSS-treated mice, and its mechanisms might be due to blunting the activation of NF-κB and NLRP3 inflammasome signaling pathways. Furthermore, Fx also modulates DSS-induced gut microbiota dysbiosis via recovering the richness and diversity of gut microbiota and reshaping the structure of gut microbiota, such as increasing the Firmicutes and Bacteroidota (F/B) ratio and elevating the relative abundance of some potential beneficial bacteria, including Lactobacillaceae and Lachnospiraceae. Overall, Fx might be developed as a promising functional ingredient to prevent colitis and maintain intestinal homeostasis.

Prebiotic proanthocyanidins inhibit bile reflux-induced esophageal adenocarcinoma through reshaping the gut microbiome and esophageal metabolome.

The gut and local esophageal microbiome progressively shift from healthy commensal bacteria to inflammation-linked pathogenic bacteria in patients with gastroesophageal reflux disease, Barrett's esophagus, and esophageal adenocarcinoma (EAC). However, mechanisms by which microbial communities and metabolites contribute to reflux-driven EAC remain incompletely understood and challenging to target. Herein, we utilized a rat reflux-induced EAC model to investigate targeting the gut microbiome-esophageal metabolome axis with cranberry proanthocyanidins (C-PAC) to inhibit EAC progression. Sprague-Dawley rats, with or without reflux induction, received water or C-PAC ad libitum (700 µg/rat/day) for 25 or 40 weeks. C-PAC exerted prebiotic activity abrogating reflux-induced dysbiosis and mitigating bile acid metabolism and transport, culminating in significant inhibition of EAC through TLR/NF-κB/TP53 signaling cascades. At the species level, C-PAC mitigated reflux-induced pathogenic bacteria (Streptococcus parasanguinis, Escherichia coli, and Proteus mirabilis). C-PAC specifically reversed reflux-induced bacterial, inflammatory, and immune-implicated proteins and genes, including Ccl4, Cd14, Crp, Cxcl1, Il6, Il1b, Lbp, Lcn2, Myd88, Nfkb1, Tlr2, and Tlr4, aligning with changes in human EAC progression, as confirmed through public databases. C-PAC is a safe, promising dietary constituent that may be utilized alone or potentially as an adjuvant to current therapies to prevent EAC progression through ameliorating reflux-induced dysbiosis, inflammation, and cellular damage.

Oral Cardiac Drug-Gut Microbiota Interaction in Chronic Heart Failure Patients: An Emerging Association.

Regardless of the currently proposed best medical treatment for heart failure patients, the morbidity and mortality rates remain high. This is due to several reasons, including the interaction between oral cardiac drug administration and gut microbiota. The relation between drugs (especially antibiotics) and gut microbiota is well established, but it is also known that more than 24% of non-antibiotic drugs affect gut microbiota, altering the microbe's environment and its metabolic products. Heart failure treatment lies mainly in the blockage of neuro-humoral hyper-activation. There is debate as to whether the administration of heart-failure-specific drugs can totally block this hyper-activation, or whether the so-called intestinal dysbiosis that is commonly observed in this group of patients can affect their action. Although there are several reports indicating a strong relation between drug-gut microbiota interplay, little is known about this relation to oral cardiac drugs in chronic heart failure. In this review, we review the contemporary data on a topic that is in its infancy. We aim to produce scientific thoughts and questions and provide reasoning for further clinical investigation.

Fabrication of zein-tamarind seed polysaccharide-curcumin nanocomplexes: their characterization and impact on alleviating colitis and gut microbiota dysbiosis in mice.

In this work, a zein-tamarind seed polysaccharide (TSP) co-delivery system was fabricated using an anti-solvent precipitation method. The formation mechanism, characterization, and effect on alleviating colitis and gut microbiota dysbiosis in mice of zein-TSP-curcumin (Z/T-Cur) nanocomplexes were investigated. Hydrogen bonding and the hydrophobic effect played a key role in the formation of Z/T-Cur nanocomplexes, and the interactions were spontaneous and driven by enthalpy. The encapsulation efficiency, loading capacity, and bioavailability increased from 60.8% (Zein-Cur) to 91.7% (Z/T-Cur1:1), from 6.1% (Zein-Cur) to 18.3% (Z/T-Cur1:1), and from 4.7% (Zein-Cur) to 20.0% (Z/T-Cur1:1), respectively. The Z/T-Cur significantly alleviated colitis symptoms in DSS-treated mice. Additionally, the prepared nanocomplexes rebalanced the gut microbiota composition of colitis mice by increasing the abundance of Akkermansia. Odoribacter and Monoglobus were rich in the Z-T-Cur treatment group, and Turicibacter and Bifidobacterium were rich in the zein-TSP treatment group. This study demonstrated that the TSP could be helpful in the targeted drug delivery system.

Prescription opioids induced microbial dysbiosis worsens severity of chronic pancreatitis and drives pain hypersensitivity.

Opioids, such as morphine and oxycodone, are widely used for pain management associated with chronic pancreatitis (CP); however, their impact on the progression and pain sensitivity of CP has never been evaluated. This report investigates the impact of opioid use on the severity of CP, pain sensitivity, and the gut microbiome. C57BL/6 mice were divided into control, CP, CP with morphine/oxycodone, and either morphine or oxycodone alone groups. CP was induced by administration of caerulein (50ug/kg/h, i.p. hourly x7, twice a week for 10 weeks). The mouse-to-pancreas weight ratio, histology, and Sirius red staining were performed to measure CP severity. Tail flick and paw pressure assays were used to measure thermal and mechanical pain. DNA was extracted from the fecal samples and subjected to whole-genome shotgun sequencing. Germ-free mice were used to validate the role of gut microbiome in sensitizing acute pancreatic inflammation. Opioid treatment exacerbates CP by increasing pancreatic necrosis, fibrosis, and immune-cell infiltration. Opioid-treated CP mice exhibited enhanced pain hypersensitivity and showed distinct clustering of the gut microbiome compared to untreated CP mice, with severely compromised gut barrier integrity. Fecal microbiota transplantation (FMT) from opioid-treated CP mice into germ-free mice resulted in pancreatic inflammation in response to a suboptimal caerulein dose. Together, these analyses revealed that opioids worsen the severity of CP and induce significant alterations in pain sensitivity and the gut microbiome in a caerulein CP mouse model. Microbial dysbiosis plays an important role in sensitizing the host to pancreatic inflammation.

Limonin alleviates high-fat diet-induced dyslipidemia by regulating the intestinal barrier via the microbiota-related ILC3-IL22-IL22R pathway.

High-fat diet (HFD)-induced dyslipidemia is frequently accompanied by gut microbiota dysbiosis and a compromised gut barrier. Enhancing the intestinal barrier function emerges as a potential therapeutic approach for dyslipidemia. The ILC3-IL22-IL22R pathway, which responds to dietary and microbial signals, has not only attracted attention for its crucial role in maintaining the intestinal barrier, but recent reports have also suggested its potential in regulating lipid metabolism. Limonin is derived from the Chinese herb Evodiae fructus, which has shown potential in ameliorating dysbiosis of serum lipids. However, its underlying mechanisms remain elusive. Consequently, targeting the ILC3-IL22-IL22R pathway to enhance intestinal barrier function holds promise as a therapeutic approach for dyslipidemia. In this study, male C57BL/6 mice were subjected to a 16-week HFD to induce dyslipidemia and concurrently administered oral limonin. We discovered that limonin supplementation dramatically reduced serum lipid profiles in HFD-fed mice, significantly curbing HFD-induced weight gain and epididymal fat accumulation. Ileal histopathological evaluation indicated limonin's ameliorative effects on HFD-induced intestinal barrier impairment. Limonin also moderated the intestinal microbiota dysbiosis, which is characterized by the elevation of Firmicutes in HFD mice, and notably amplified the abundance of probiotic Lactobacillus. In addition, supported by flow cytometry and other analyses, we observed that limonin upregulated the ILC3-IL22-IL22R pathway, enhancing phosphorylated STAT3 (pSTAT3) in intestinal epithelial cells (IECs), thereby reducing lipid transporter expression. In conclusion, our study revealed that limonin exerted a promising preventive effect against HFD-induced dyslipidemia by the mitigation of the intestinal barrier function and intestinal microbiota, and its mechanism was related to the upregulation of the ILC3-IL22-IL22R pathway.

Modulation of cellular metabolism and alleviation of bacterial dysbiosis by Aconiti Lateralis Radix Praeparata in non-small cell lung cancer treatment.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a highly prevalent and fatal form of lung cancer. In China, Aconiti Lateralis Radix Praeparata (Fuzi in Chinese), derived from the lateral root of Aconitum carmichaeli Debx. (Ranunculaceae, Aconitum), is extensively prescribed to treat cancer in traditional medicine and clinical practice. However, the precise mechanism by which Fuzi treats NSCLC remains unknown. PURPOSE: This article aims to assess the efficacy of Fuzi against NSCLC and elucidate its underlying mechanism. METHODS: Marker ingredients of Fuzi decoction were quantified using UPLC-TSQ-MS. The effectiveness of Fuzi on NSCLC was evaluated using a xenograft mouse model. Subsequently, a comprehensive approach involving network pharmacology, serum metabolomics, and 16S rDNA sequencing was employed to investigate the anti-NSCLC mechanism of Fuzi. RESULTS: Pharmacological evaluation revealed significant tumour growth inhibition by Fuzi, accompanied by minimal toxicity. Network pharmacology identified 29 active Fuzi compounds influencing HIF-1, PI3K/Akt signalling, and central carbon metabolism in NSCLC. Integrating untargeted serum metabolomics highlighted 30 differential metabolites enriched in aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate metabolism, and the tricarboxylic acid (TCA) cycle. Targeted serum metabolomics confirmed elevated glucose content and reduced levels of pyruvate, lactate, citrate, α-ketoglutarate, succinate, fumarate, and malate following Fuzi administration. Furthermore, 16S rDNA sequencing assay showed that Fuzi ameliorated the dysbiosis after tumorigenesis, decreased the abundance of Proteobacteria, and increased that of Firmicutes and Bacteriodetes. PICRUSt analysis revealed that Fuzi modulated the pentose phosphate pathway of the gut microbiota. Spearman correlation showed that Proteobacteria and Escherichia_Shigella accelerated the TCA cycle, whereas Bacteroidota, Bacteroides, and Lachnospiraceae_NK4A136_group suppressed the TCA cycle. CONCLUSIONS: This study firstly introduces a novel NSCLC mechanism involving Fuzi, encompassing energy metabolism and intestinal flora. It clarifies the pivotal role of the gut microbiota in treating NSCLC and modulating the TCA cycle. Moreover, these findings offer valuable insights for clinical practices and future research of Fuzi against NSCLC.

Mulberry (Morus alba L.) leaf water extract attenuates type 2 diabetes mellitus by regulating gut microbiota dysbiosis, lipopolysaccharide elevation and endocannabinoid system disorder.

ETHNOPHARMACOLOGICAL RELEVANCE: Mulberry (Morus alba L.) leaf is a well-known herbal medicine and has been used to treat diabetes in China for thousands of years. Our previous studies have proven mulberry leaf water extract (MLWE) could improve type 2 diabetes mellitus (T2D). However, it is still unclear whether MLWE could mitigate T2D by regulating gut microbiota dysbiosis and thereof improve intestinal permeability and metabolic dysfunction through modulation of lipopolysaccharide (LPS) and endocannabinoid system (eCBs). AIM OF STUDY: This study aims to explore the potential mechanism of MLWE on the regulation of metabolic function disorder of T2D mice from the aspects of gut microbiota, LPS and eCBs. MATERIALS AND METHODS: Gut microbiota was analyzed by high-throughput 16S rRNA gene sequencing. LPS, N-arachidonoylethanolamine (AEA) and 2-ararchidonylglycerol (2-AG) contents in blood were determined by kits or liquid phase chromatography coupled with triple quadrupole tandem mass spectrometry, respectively. The receptors, enzymes or tight junction protein related to eCBs or gut barrier were detected by RT-PCR or Western blot, respectively. RESULTS: MLWE reduced the serum levels of AEA, 2-AG and LPS, decreased the expressions of N-acylphophatidylethanolamine phospholipase D, diacylglycerol lipase-α and cyclooxygenase 2, and increased the expressions of fatty acid amide hydrolase (FAAH), N-acylethanolamine-hydrolyzing acid amidase (NAAA), alpha/beta hydrolases domain 6/12 in the liver and ileum and occludin, monoacylglycerol lipase and cannabinoid receptor 1 in the ileum of T2D mice. Furthermore, MLWE could change the abundances of the genera including Acetatifactor, Anaerovorax, Bilophila, Colidextribacter, Dubosiella, Gastranaerophilales, Lachnospiraceae_NK4A136_group, Oscillibacter and Rikenella related to LPS, AEA and/or 2-AG. Moreover, obvious improvement of MLWE treatment on serum AEA level, ileum occludin expression, and liver FAAH and NAAA expression could be observed in germ-free-mimic T2D mice. CONCLUSION: MLWE could ameliorate intestinal permeability, inflammation, and glucose and lipid metabolism imbalance of T2D by regulating gut microbiota, LPS and eCBs.

Potential effects of the most prescribed drugs on the microbiota-gut-brain-axis: A review.

The link between drug-induced dysbiosis and its influence on brain diseases through gut-residing bacteria and their metabolites, named the microbiota-gut-brain axis (MGBA), remains largely unexplored. This review investigates the effects of commonly prescribed drugs (metformin, statins, proton-pump-inhibitors, NSAIDs, and anti-depressants) on the gut microbiota, comparing the findings with altered bacterial populations in major brain diseases (depression, multiple sclerosis, Parkinson's and Alzheimer's). The report aims to explore whether drugs can influence the development and progression of brain diseases via the MGBA. Central findings indicate that all explored drugs induce dysbiosis. These dysbiosis patterns were associated with brain disorders. The influence on brain diseases varied across different bacterial taxa, possibly mediated by direct effects or through bacterial metabolites. Each drug induced both positive and negative changes in the abundance of bacteria, indicating a counterbalancing effect. Moreover, the above-mentioned drugs exhibited similar effects, suggesting that they may counteract or enhance each other's effects on brain diseases when taken together by comorbid patients. In conclusion, the interplay of bacterial species and their abundances may have a greater impact on brain diseases than individual drugs or bacterial strains. Future research is needed to better understand drug-induced dysbiosis and the implications for brain disease pathogenesis, with the potential to develop more effective therapeutic options for patients with brain-related diseases.

Herbal medicine and gut microbiota: exploring untapped therapeutic potential in neurodegenerative disease management.

The gut microbiota that exists in the human gastrointestinal tract is incredibly important for the maintenance of general health as it contributes to multiple aspects of host physiology. Recent research has revealed a dynamic connection between the gut microbiota and the central nervous system, that can influence neurodegenerative diseases (NDs). Indeed, imbalances in the gut microbiota, or dysbiosis, play a vital role in the pathogenesis and progression of human diseases, particularly NDs. Herbal medicine has been used for centuries to treat human diseases, including NDs. These compounds help to relieve symptoms and delay the progression of NDs by improving intestinal barrier function, reducing neuroinflammation, and modulating neurotransmitter production. Notably, herbal medicine can mitigate the progression of NDs by regulating the gut microbiota. Therefore, an in-depth understanding of the potential mechanisms by which herbal medicine regulates the gut microbiota in the treatment of NDs can help explain the pathogenesis of NDs from a novel perspective and propose novel therapeutic strategies for NDs. In this review, we investigate the potential neuroprotective effects of herbal medicine, focusing on its ability to regulate the gut microbiota and restore homeostasis. We also highlight the challenges and future research priorities of the integration of herbal medicine and modern medicine. As the global population ages, access to this information is becoming increasingly important for developing effective treatments for these diseases.

The bladder microbiota is not significantly altered by intravesical BCG therapy.

INTRODUCTION: Bladder microbiota dysbiosis has been associated with several urological disorders. However, dysbiosis markers in bladder cancer have not been identified and little is known about the effect of Bacillus Calmette-Guérin (BCG) intravesical therapy on the bladder microbiota. In this study, we compared the bladder microbiota of patients with non-muscle-invasive bladder cancer (NMIBC) undergoing BCG therapy to nononcological controls. We also longitudinally analyzed the impact of BCG therapy on the bladder microbiota of NMIBC patients and addressed whether bladder microbiota is associated with BCG efficacy. METHODS: We collected catheterized urine samples from males with intermediate/high-risk NMIBC (cancer group, n = 32) or benign prostatic hyperplasia (control group, n = 41). The cancer group also provided urine samples during and after BCG induction. We used 16S rRNA gene sequencing to characterize the bladder microbiota. Bladder microbiota parameters, such as diversity and taxonomic composition, were compared between groups and associated with clinicopathological data and BCG efficacy. RESULTS: We observed no significant differences between the bladder microbiota of NMIBC patients and controls. BCG intravesical instillations did not significantly alter the bladder microbiota of NMIBC patients, and BCG was rarely detected in the bladder during and after BCG therapy. Microbiota diversity and overall composition before BCG induction did not influence disease persistence at 3 months. However, higher abundance of Lactobacillus, Streptococcus, and Cutibacterium in the pre-BCG bladder microbiota was associated with BCG effectiveness. CONCLUSION: We were unable to identify markers of bladder microbiota dysbiosis among male NMIBC patients. Moreover, we demonstrated for the first time using longitudinally collected samples that BCG cannot persist in the bladder microbiota nor significantly alter its diversity and composition. The associations found between bladder microbes and BCG efficacy highlight the potential of microbial-based therapeutic and risk-stratification strategies in the intermediate/high-risk NMIBC setting.

Metformin, Cognitive Function, and Changes in the Gut Microbiome.

The decline in cognitive function and the prevalence of neurodegenerative disorders are among the most serious threats to health in old age. The prevalence of dementia has reached 50 million people worldwide and has become a major public health problem. The causes of age-related cognitive impairment are multiple, complex, and difficult to determine. However, type 2 diabetes (T2D) is linked to an enhanced risk of cognitive impairment and dementia. Human studies have shown that patients with T2D exhibit dysbiosis of the gut microbiota. This dysbiosis may contribute to the development of insulin resistance and increased plasma lipopolysaccharide concentrations. Metformin medication mimics some of the benefits of calorie restriction and physical activity, such as greater insulin sensitivity and decreased cholesterol levels, and hence may also have a positive impact on aging in humans. According to recent human investigations, metformin might partially restore gut dysbiosis related to T2D. Likewise, some studies showed that metformin reduced the risk of dementia and improved cognition, although not all studies are concordant. Therefore, this review focused on those human studies describing the effects of metformin on the gut microbiome (specifically the changes in taxonomy, function, and circulating metabolomics), the changes in cognitive function, and their possible bidirectional implications.

Effect of chronic low-dose treatment with chitooligosaccharides on microbial dysbiosis and inflammation associated chronic ulcerative colitis in Balb/c mice.

The study aimed to investigate the potential of low dose chitooligosaccharide (COS) in ameliorating dextran sodium sulfate (DSS) induced chronic colitis by regulating microbial dysbiosis and pro-inflammatory responses. Chronic colitis was induced in BALB/c mice by DSS (4% w/v, 3 cycles of 5 days) administration. The mice were divided into four groups: vehicle, DSS, DSS + mesalamine and DSS+COS. COS and mesalamine were administered orally, daily once, from day 1 to day 30 at a dose of 20 mg/kg and 50 mg/kg respectively. The disease activity index (DAI), colon length, histopathological score, microbial composition, and pro-inflammatory cytokine expression were evaluated. COS (20 mg/kg, COSLow) administration reduced the disease activity index, and colon shortening, caused by DSS significantly. Furthermore, COSLow restored the altered microbiome in the gut and inhibited the elevated pro-inflammatory cytokines (IL-1 and IL-6) in the colon against DSS-induced chronic colitis in mice. Moreover, COSLow treatment improved the probiotic microflora thereby restoring the gut homeostasis. In conclusion, this is the first study where microbial dysbiosis and pro-inflammatory responses were modulated by chronic COSLow treatment against DSS-induced chronic colitis in Balb/c mice. Therefore, COS supplementation at a relatively low dose could be efficacious for chronic inflammatory bowel disease.