Regulation Of Microbiota Research Articles

Chondroitin sulfate modulates oxidative stress and inflammation in the substantia nigra via gut microbiota regulation: Mechanistic insights into Parkinson's disease treatment

Hydrogen sulfide (H2S) is a bioactive gas with potential neuroprotective properties. This study explores the therapeutic efficacy of chondroitin sulfate (CS) in a Parkinson's disease (PD) mouse model by evaluating its impact on behavior, gut microbiota composition, substantia nigra (SN) pathology, oxidative stress, and inflammation. Behavioral tests indicate that CS improves cognitive function and learning abilities in PD mice. Gut microbiota analysis and fecal H2S content measurement reveal that CS fosters the growth of Desulfovibrio and boosts H2S production, respectively. Further examination shows that CS treatment enhances antioxidant defenses, reduces inducible nitric oxide synthase (iNOS)-mediated inflammation, and alleviates PD-related pathology and α-synuclein overexpression in the SN. These findings suggest that CS modulates the gut microbiota and its metabolic product, H2S, potentially improving PD symptoms through the gut-brain axis.

Ameliorative effects of Akkermansia muciniphila on anxiety-like behavior and cognitive deficits in a rat model of Alzheimer’s disease

Alzheimer’s Disease (AD) is the primary neurodegenerative disorder in the elderly, lacking a definitive treatment. The gut microbiota influences the gut-brain axis by aiding in hypothalamic–pituitary–adrenal (HPA) axis development and neuromodulator production. Research links AD and gut microbiota, suggesting gut microbiota regulation could be a therapeutic approach for AD. This study explores Akkermansia muciniphila’s impact on preventing AD. This research investigates the effect of A. muciniphila consumption (1 × 109 CFU) on tau protein-induced AD rats compared to a control group. Rats were divided into four groups: sham, sham + Akk, AD (tau-induced rats), and AD + Akk (tau-induced rats treated with A. muciniphila). A. muciniphila gavage lasted five weeks. Rats underwent qRT-PCR analysis to assess mRNA expression of pro-inflammatory factors (TNF-α, IL-6, IL-1β, IFN-γ) in the hippocampus. Behavioral tests included Morris Water Maze (MWM), Passive Avoidance Memory Test (Shuttle box), Elevated Plus Maze (EPM), and marble burying. After five weeks of A. muciniphila treatment, anxiety-like behavior significantly decreased. The AD group receiving A. muciniphila showed improved spatial and recognition memory compared to the AD group. Pro-inflammatory cytokine levels (TNF-α, IL-1β, IL-6, IFN-γ) decreased. A. muciniphila effectively reduces cognitive impairments and anxiety-related behavior, showing promise as an AD therapeutic by influencing the gut-brain axis.

Bamboo dietary cellulose emulsified camellia oil: Potential synergistic regulation of human gut microbiota in vitro

The medical applications of camellia oil are limited due to the instability of its active ingredients throughout the digestive tract. Pickering emulsion is one of the promising strategies to address this issue, yet the synergistic effect of oil and emulsifier phases on modulation of human gut microbiota is still unclear. Herein, high crystallinity rod-like bamboo nanocellulose (BNC) with a major diameter of 100–170 nm was prepared. BNC served as emulsifier to stabilize camellia oil emulsion and allowed for a stable storage period of more than 70 days at 4 °C. The BNC loading and ratio of water/oil attributed important effects on emulsion stability. During the investigations interrogating fermentation by gut microbiota in vitro, the concentrations of SCFAs (n-valeric, i-butyric, and i-valeric acids) were elevated in the emulsion treated groups. Additionally, proliferation of Dorea and Phascolarctobacterium, and inhibition of Desulfovibrio and Bacteroides were the key features through the emulsion intervention. Functional metabolic pathway analysis demonstrated the significant enhancement in carbohydrate metabolism and membrane transport. These findings suggested that insoluble BNC-stabilized camellia oil emulsion could be used as a dietary collocation for potential applications involving medical delivery system and synergistic modulation of gut microbiota.

Sodium Butyrate Ameliorates Postoperative Delirium by Regulating Gut Microbiota Dysbiosis to Inhibit Astrocyte Activation in Aged Mice.

Postoperative delirium (POD) is a common complication in elderly surgical patients, with limited targeted interventions due to incomplete understanding of its pathophysiological mechanisms. Central nervous system (CNS) inflammation, involving glial cell activation, particularly astrocytes, is considered crucial in POD development. Butyrate, a four-carbon fatty acid, has shown protective effects in CNS diseases, but its potential in mitigating POD remains unclear. This study aimed to investigate the impact of sodium butyrate on POD in aged mice. Behavioral tests, including open field, Y maze, and food burying tests, demonstrated that sodium butyrate preconditioning ameliorated laparotomy-induced delirium in aged mice. Pre-treatment with sodium butyrate inhibited astrocyte activation in the hippocampus, reduced interleukin-1β (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) expression levels, and protected hippocampal neurons. Furthermore, the study revealed a connection between gut microbiota regulation and central neuroprotective effects mediated by astrocyte activation inhibition. Sodium butyrate improved the intestinal morphological barrier by rebalancing gut microbiota, inhibiting Proteobacteria and Actinobacteria, reducing Allobaculum and Bacteroides abundance, and increasing Oscillospira abundance. This regulation decreased gut permeability, limiting the entry of toxic substances into the bloodstream, thereby reducing inflammation spread and astrocyte overactivation, leading to central anti-inflammatory effects. In conclusion, sodium butyrate may ameliorate POD by inhibiting astrocyte-mediated neuroinflammation through gut microbiota rebalancing.

Chondroitin Sulfate from Halaelurus burgeri Skin Inhibits Hepatic Endoplasmic Reticulum Stress and Inflammation, and Regulates Gut Microbiota.

Previous study has demonstrated the chemical structure of chondroitin sulfate (CHS) from Halaelurus burgeri skin and its effects on insulin resistance. However, the precise impact of this phenomenon on endoplasmic reticulum (ER) stress and inflammation, which contribute to insulin resistance, remains unclear. This study is to investigate the impact of CHS on ER stress, inflammatory response and signaling, and gut microbiota in high-fat diet (HFD)-fed mice. HFD-fed C57BL/6J mice receive dietary gavage intervention of CHS for 18 weeks. Blood, liver tissue, and feces are harvested for further investigation. Results show that CHS inhibits ER stress, accompanied by lowered blood glucose, nitric oxide (NO), reactive oxygen (ROS), and free fatty acids (FFA) levels, and increases hepatic glycogen accumulation. Moreover, hepatic inflammation is improved by CHS treatment via inactivation of Toll-like receptor 4 (TLR4) signaling and its downstream c-jun N-terminal kinase (JNK) and nuclear factor kappa B (NFκB) pathways. Additionally, CHS regulates gut microbiota, particularly the decline in the Firmicutes to Bacteroidetes ratio. CHS also lowers fecal lipopolysaccharide and elevates several fecal short chain fatty acids. These findings suggest that CHS from H. burgeri skin may be an alternative functional food supplement for anti-ER stress, anti-inflammtion, and regulation of gut microbiota.

Therapeutic Role of Probiotics Against Environmental-Induced Hepatotoxicity: Mechanisms, Clinical Perspectives, Limitations, and Future.

Hepatotoxicity is one of the biggest health challenges, particularly in the context of liver diseases, often aggravated by gut microbiota dysbiosis. The gut-liver axis has been regarded as a key idea in liver health. It indicates that changes in gut flora caused by various hepatotoxicants, including alcoholism, acetaminophen, carbon tetrachloride, and thioacetamide, can affect the balance of the gut's microflora, which may lead to increased dysbiosis and intestinal permeability. As a result, bacterial endotoxins would eventually enter the bloodstream and liver, causing hepatotoxicity and inducing inflammatory reactions. Many treatments, including liver transplantation and modern drugs, can be used to address these issues. However, because of the many side effects of these approaches, scientists and medical experts are still hoping for a therapeutic approach with fewer side effects and more positive results. Thus, probiotics have become well-known as an adjunctive strategy for managing, preventing, or reducing hepatotoxicity in treating liver injury. By altering the gut microbiota, probiotics offer a secure, non-invasive, and economical way to improve liver health in the treatment of hepatotoxicity. Through various mechanisms such as regulation of gut microbiota, reduction of pathogenic overgrowth, suppression of inflammatory mediators, modification of hepatic lipid metabolism, improvement in the performance of the epithelial barrier of the gut, antioxidative effects, and modulation of mucosal immunity, probiotics play their role in the treatment and prevention of hepatotoxicity. This review highlights the mechanistic effects of probiotics in environmental toxicants-induced hepatotoxicity and current findings on this therapeutic approach's experimental and clinical trials.

A Highly Atom-Efficient Prodrug Approach to Generate Synergy between H2S and Nonsteroidal Anti-inflammatory Drugs and Improve Safety.

Efforts to synergize hydrogen sulfide (H2S) with NSAIDs have faced challenges due to complex structural entities and independent release kinetics. This study presents a highly atom-efficient approach of using a thiocarboxylic acid (thioacid) as a novel H2S releasing precursor and successfully employs it to modify NSAIDs, which offers several critical advantages. First, thioacid-modified NSAID is active in inhibiting cyclooxygenase, sometimes with improved potency. Second, this prodrug approach avoids introducing extra structural moieties, allowing for the release of only the intended active principals. Third, the release of H2S and NSAID is concomitant, thus optimally synchronizing the concentration profiles of the two active principals. The design is based on our discovery that esterases can directly and efficiently hydrolyze thiocarboxylic acids, enabling controlled release H2S. This study demonstrates the proof of principle through synthesizing analogs, assesses release kinetics, enzyme inhibition, and pharmacological efficacy, and evaluates toxicity and gut microbiota regulation in animal models.

Role of tenofovir dipivoxil in gut microbiota recovery from HBV-infection induced dysbiosis

BackgroundStudies have found dysbiosis of the gut microbiota in individuals infected with the hepatitis B virus (HBV). Tenofovir dipivoxil (TDF) is one of the preferred oral antiviral drugs used for the treatment of chronic hepatitis B (CHB), but the extent to which TDF is able to affect the gut microbiota and inflammatory factors of a patient remains largely unexplored. In this study, we collected stool samples from HBV patients prior to medication and from CHB patients treated with TDF.ResultsThe gut microbiota and inflammatory factors were assessed in 42 healthy subjects (HC group), 109 HBV-infected subjects, including 48 CHB patients who were not medicated with nucleoside analogue drugs (No-NAs group), and 61 CHB patients who were medicated with TDF (TDF group). 16 S rRNA sequencing revealed that TDF treatment caused significant changes in the gut microbiota of HBV-infected individuals; however, the gut microbiota of HBV-infected individuals did not fully recover to a pre-dysbiosis state. The relative abundance of Bacteroidota gradually decreased from the HC group to the No-NAs and TDF groups. The relative abundance of Fusobacteriota was significantly higher in the No-NAs group than in the HC group. At the genus level, Dialister, Eubacterium_hallii_group, Halomonas, Collinsella, Sphingomonas, Xanthomonadaceae_unclassified, and Rhizobiaceae_unclassified were overrepresented; while the abundance of Bacteroides and Fusobacterium decreased significantly in the No-NAs and TDF groups.ConclusionsThis study showed that TDF treatment significantly improved the regulation of the gut microbiota and aided in dysbiosis recovery. We did not observe significant improvement in serum inflammatory factor concentrations, which may be related to the relatively short duration of TDF administration in this study.

Regulation of Cecal Microbiota and Improvement of Blood Lipids Using Walnut Non-Dairy Creamer in High-Fat Mice: Replacing Traditional Non-Dairy Creamer.

Non-dairy creamer is a class of microencapsulated powdered fats and oils that are widely used in the food industry. However, the oils used in it are hydrogenated vegetable oils, which contain large amounts of saturated fatty acids and are extremely harmful to the human body. This study investigated the effects of replacing hydrogenated vegetable oil with walnut oil to prepare walnut non-dairy creamer on lipid levels and intestinal microorganisms in mice. The results show that low-dose walnut non-dairy creamer significantly decreased the contents of TC and TG in serum and increased the content of HDL-C (p < 0.01). The contents of MDA, ALT, and AST were significantly decreased, while the content of SOD was increased (p < 0.01). The abundance of Firmicutes in the walnut non-dairy creamer group decreased, and the abundance of Bacteroidetes/Firmicutes (B/F) increased, which significantly increased the richness of Lactobacillus and Oscillospira (p < 0.01). Allobaculum richness was significantly decreased (p < 0.01). In conclusion, a low dose of walnut non-dairy creamer can effectively promote the metabolism of blood lipids in vivo, alleviate oxidative stress injury and lipid accumulation damage to mouse hepatocytes, and ameliorate the adverse effects of a high-fat diet on the intestinal microbiota of mice. This study provides a theoretical basis for the replacement of traditional non-dairy creamer and the research and development of walnut deep processing.

Progesterone promotes CXCl2-dependent vaginal neutrophil killing by activating cervical resident macrophage-neutrophil crosstalk.

Vaginal infections in women of reproductive age represent a clinical dilemma with significant socioeconomic implications. The current understanding of mucosal immunity failure during early pathogenic invasions that allows the pathogen to grow and thrive is far from complete. Neutrophils infiltrate most tissues following circadian patterns as part of normal repair, regulation of microbiota, or immune surveillance and become more numerous after infection. Neutrophils are responsible for maintaining vaginal immunity. Specific to the vagina, neutrophils continuously infiltrate at high levels, although during ovulation, they retreat to avoid sperm damage and permit reproduction. Here we show that, after ovulation, progesterone promotes resident vaginal macrophage-neutrophil crosstalk by upregulating Yolk sac early fetal organs (FOLR2+) macrophage CXCl2 expression, in a TNFA-patrolling monocyte-derived macrophage-mediated (CX3CR1hiMHCIIhi-mediated) manner, to activate the neutrophils' capacity to eliminate sex-transmitted and opportunistic microorganisms. Indeed, progesterone plays an essential role in conciliating the balance between the commensal microbiota, sperm, and the threat of pathogens because progesterone not only promotes a flurry of neutrophils but also increases neutrophilic fury to restore immunity after ovulation to thwart pathogenic invasion after intercourse. Therefore, modest progesterone dysregulations could lead to a suboptimal neutrophilic response, resulting in insufficient mucosal defense and recurrent unresolved infections.

Differences in salivary microbiome among children with tonsillar hypertrophy and/or adenoid hypertrophy.

Children diagnosed with severe tonsillar hypertrophy display discernible craniofacial features distinct from those with adenoid hypertrophy, prompting illuminating considerations regarding microbiota regulation in this non-inflammatory condition. The present study aimed to characterize the salivary microbial profile in children with tonsillar hypertrophy and explore the potential functionality therein. A total of 112 children, with a mean age of 7.79 ± 2.41 years, were enrolled and divided into the tonsillar hypertrophy (TH) group (n = 46, 8.4 ± 2.5 years old), adenoid hypertrophy (AH) group (n = 21, 7.6 ± 2.8 years old), adenotonsillar hypertrophy (ATH) group (n = 23, 7.2 ± 2.1 years old), and control group (n = 22, 8.6 ± 2.1 years old). Unstimulated saliva samples were collected, and microbial profiles were analyzed by 16S rRNA sequencing of V3-V4 regions. Diversity and composition of salivary microbiome and the correlation with parameters of overnight polysomnography and complete blood count were investigated. As a result, children with tonsillar hypertrophy had significantly higher α-diversity indices (P＜0.05). β-diversity based on Bray-Curtis distance revealed that the salivary microbiome of the tonsillar hypertrophy group had a slight separation from the other three groups (P＜0.05). The linear discriminant analysis effect size (LEfSe) analysis indicated that Gemella was most closely related to tonsillar hypertrophy, and higher abundance of Gemella, Parvimonas, Dialister, and Lactobacillus may reflect an active state of immune regulation. Meanwhile, children with different degrees of tonsillar hypertrophy shared similar salivary microbiome diversity. This study demonstrated that the salivary microbiome in pediatric tonsillar hypertrophy patients had different signatures, highlighting that the site of upper airway obstruction primarily influences the salivary microbiome rather than hypertrophy severity.IMPORTANCETonsillar hypertrophy is the most frequent cause of upper airway obstruction and one of the primary risk factors for pediatric obstructive sleep apnea (OSA). Studies have discovered that children with isolated tonsillar hypertrophy exhibit different craniofacial morphology features compared with those with isolated adenoid hypertrophy or adenotonsillar hypertrophy. Furthermore, characteristic salivary microbiota from children with OSA compared with healthy children has been identified in our previous research. However, few studies provided insight into the relationship between the different sites of upper airway obstruction resulting from the enlargement of pharyngeal lymphoid tissue at different sites and the alterations in the microbiome. Here, to investigate the differences in the salivary microbiome of children with tonsillar hypertrophy and/or adenoid hypertrophy, we conducted a cross-sectional study and depicted the unique microbiome profile of pediatric tonsillar hypertrophy, which was mainly characterized by a significantly higher abundance of genera belonging to phyla Firmicutes and certain bacteria involving in the immune response in tonsillar hypertrophy, offering novel perspectives for future related research.

Lactic Acid Bacterial Fermentation of Esterified Agave Fructans in Simulated Physicochemical Colon Conditions for Local Delivery of Encapsulated Drugs

Understanding drug release in the colon is fundamental to developing efficient treatments for colon-related diseases, while unraveling the relationship between the colonic microbiota and excipients is crucial to unveiling the effect of biomaterials on the release of drugs. In this contribution, the bio-release of ibuprofen (encapsulated in acetylated and palmitoylated agave fructans) was evaluated by fermentation with lactic acid bacteria in simulated physicochemical (pH and temperature) colon conditions. It was observed that the size of the acyl chain (1 in acetyl and 15 in palmitoyl) was critical both in the growth of the microorganisms and in the release of the drug. For example, both the bacterial growth and the release of ibuprofen were more favored with acetylated fructan microspheres. Among the microorganisms evaluated, Bifidobacterium adolescentis and Lactobacillus brevis showed great potential as probiotics useful to release drugs from modified fructans. The production of short-chain fatty acids (lactic, acetic, and propionic acids) in the course of fermentations was also determined, since such molecules have a positive effect both on colon-related diseases and on the regulation of the intestinal microbiota. It was found that a higher concentration of acetate is related to a lower growth of bacteria and less release of ibuprofen.

Physicochemical properties, structure and regulatory effect on gut microbiota of dietary fiber extracted from soybean meal via dry fractionation

Currently, dry fractionation is employed to extract dietary fiber (DF) from food processing bypuroduct owing to its advantages of low energy and eco-friendly. Procedures of dry fractionation mainly include milling and air classification. Soybean meal (SBM) is a processing byproduct rich in DF. Few studies have used dry fractionation to extract SBM dietary fiber (SMF), and the physicochemical properties, structural characteristics, and activity of SMF extracted via dry fractionation remain unclear. Herein, SMF was prepared via dry fractionation and results showed that compared with that of SBM without pores and high crystallinity, SMF had loose and porous surface and low crystallinity. Moreover, the water holding capacity, oil holding capacity and swelling ability of SMF were significantly higher than SBM. After 24 h of in vitro fecal fermentation, the SMF group produced abundant short chain fatty acids (SCFA) such as acetic, propionic, and butyric acids and the total SCFA production was substantially higher than that in the inulin (INL) group. SMF also promoted the relative abundance of beneficial bacteria such as Prevotella, Dialister, and Bifidobacterium and reduced the relative abundance of harmful bacteria such as Escherichia–Shigella. In conclusion, SMF extracted via dry fractionation can significantly alter the relative abundance and diversity of gut microbiota and promote the production of SCFA, which is conducive to the regulation of the human gut microbiota. This study can provide insights into the preparation of DF via dry fractionation and provide theoretical basis for SMF to be used as a prebiotic.

Intestinal and hepatic benefits of BBR-EVO on DSS-induced experimental colitis in mice.

Ulcerative colitis (UC), characterized by disrupted intestinal barrier integrity and chronic inflammation, was modeled in mice via dextran sulfate sodium (DSS) induction. This study explored the therapeutic potential of berberine-evodiamine (BBR-EVO), bioactive components of the traditional Chinese medicine Yulian decoction, in DSS colitis. BBR-EVO intervention ameliorated weight loss, diarrhea, colonic shortening, and histopathological damage in colitic mice. The substance increased antioxidant activity while reducing high levels of pro-inflammatory cytokines in the colon, including as TNF-α, IL-1β, and IL-6. BBR-EVO inhibited the DSS-induced decrease in the tight junction proteins ZO-1 and occludin, according to immunohistochemistry. 16S rRNA sequencing demonstrated BBR-EVO partially attenuated DSS-elicited intestinal dysbiosis, reducing opportunistic pathogens and restoring diminished beneficial taxa. Critically, BBR-EVO alleviated secondary hepatic injury in colitic mice, mitigating immune cell infiltration, oxidative stress, cytokine production, and ultrastructural damage, likely by beneficially modulating gut-liver crosstalk. This study reveals BBR-EVO, derived from a traditional Chinese medicine, confers multi-target protective effects in experimental colitis and associated hepatic pathology, warranting further evaluation as a potential therapy for inflammatory bowel diseases like UC. The mechanisms may involve simultaneous augmentation of intestinal barrier integrity, inhibition of inflammation, microbiota regulation, and gut-liver axis optimization.

Long-term Pu-erh tea alleviates inflammatory bowel disease via the regulation of intestinal microbiota and maintaining the intestinal mucosal barrier

Long-term Pu-erh tea alleviates inflammatory bowel disease via the regulation of intestinal microbiota and maintaining the intestinal mucosal barrier

Maidong Dishao Decoction mitigates submandibular gland injury in NOD mice through modulation of gut microbiota and restoration of Th17/Treg immune balance

BackgroundPrimary Sjogren's syndrome (pSS) is a common chronic autoimmune disease that presents limited treatment options and poses significant challenges for patients. Maidong Dishao Decoction (MDDST), a traditional Chinese medicine compound, has demonstrated potential in alleviating dryness symptoms associated with pSS. Therefore, it is important to study the specific mechanism of its therapeutic effect. ObjectiveThis study aims to investigate the effects of MDDST on gut microbiota, short-chain fatty acids (SCFAs), and the Th17/Treg immune balance in non-obese diabetes (NOD) mice. MethodsThe study employed ultrahigh-performance liquid chromatography coupled with quadrupole-exactive mass spectrometry (UHPLC-QE-MS) to identify the primary components of MDDST. Subsequently, hematoxylin and eosin (HE) staining, enzyme-linked immunosorbent assays (ELISA), and flow cytometry analyses were conducted to evaluate the therapeutic effects of MDDST in NOD mice. Additionally, 16S rDNA sequencing and gas chromatography-mass spectrometry (GC-MS) were utilized to assess the influence of MDDST on gut microbiota and SCFAs. Finally, fecal microbiota transplantation (FMT) and SCFA-based interventions were performed to elucidate the mechanisms through which MDDST exerts its effects. ResultsThe research findings demonstrate that MDDST exerts therapeutic effects on NOD mice, primarily manifested as reduced inflammation, decreased water intake, ameliorated pathological changes and lowered levels of Sjogren's syndrome antigen A (SSA) and immunoglobulin G (IgG). Additionally, MDDST significantly decreased serum levels of interleukin-6 (IL-6) and interleukin-17 (IL-17), while enhancing levels of interleukin-10 (IL-10) and transforming growth factor beta (TGF-β), thereby regulating the Th17/Treg immune balance. Further investigations revealed that MDDST treatment induces alterations in gut microbiota composition and elevates SCFA levels in the gut. Subsequent FMT and SCFA intervention experiments demonstrated a downregulation of pSS-related phenotypes. ConclusionIn summary, MDDST demonstrates protective effects against pSS by restoring the balance between Th17 and Treg cells. The therapeutic effects can be partially attributed to its regulation of gut microbiota and SCFAs. Our finding provides a new option for treating pSS.

Carbonic anhydrase 2 mediates anti-obesity effects of black tea as thermogenic activator

Obesity is a metabolic disorder due to over-accumulation of adipose tissue and ultimately becomes a “disease”. Brown adipose tissue (BAT) thermogenesis and white adipose tissue (WAT) browning emerge as a potential strategy of anti-obesity by dissipating energy as heat. However, drugs based on adipose tissue thermogenesis have not been successfully approved yet. In current study, we found that black tea extract (BTE) obtained by patent-authorized manufacturing process prevented body weight gain as novel thermogenic activator with reduction of adiposity, improvement of adipose distribution, and glucose metabolism improvement in diet-induced obesity mice. Mechanismly, anti-obesity effect of BTE depends on promoting BAT thermogenesis and WAT browning with upregulation of uncoupling protein 1 (UCP1), especially visceral adipose tissue (VAT) with browning resistance. Specifically, utilizing in silico approach of network pharmacology and molecular docking, we identified carbonic anhydrase 2 (CA2) in nitrogen metabolism as anti-obesity target of BTE and further elucidated that protein kinase B (AKT) signaling pathway linked CA2 and UCP1. Meanwhile gut microbiota regulation may prompt the CA2-dependent thermogenesis activation. Our findings demonstrated anti-obesity effect of BTE as thermogenic activator through CA2-mediated BAT thermogenesis and WAT browning via CA2-AKT-UCP1 signaling pathway, which could be developed as promising anti-obesity agent with good safety and efficacy.

Neuroprotective effects of mesenchymal stromal cells in mouse models of Alzheimer’s Disease: The Mediating role of gut microbes and their metabolites via the Microbiome-Gut-Brain axis

The intricacy and multifaceted nature of Alzheimer’s disease (AD) necessitate therapies that target multiple aspects of the disease. Mesenchymal stromal cells (MSCs) emerge as potential agents to mitigate AD symptoms; however, whether their therapeutic efficacy involves modulation of gut microbiota and the microbiome-gut-brain axis (MGBA) remains unexplored. In this study, we evaluated the effects of three distinct MSCs types—derived from the umbilical cord (UCMSC), dental pulp (SHED), and adipose tissue (ADSC)—in an APP/PS1 mouse model of AD. In comparison to saline control, MSCs administration resulted in a significant reduction of behavioral disturbances, amyloid plaques, and phosphorylated tau in the hippocampus and frontal cortex, accompanied by an increase in neuronal count and Nissl body density across AD-afflicted brain regions. Through 16S rRNA gene sequencing, we identified partial restoration of gut microbial balance in AD mice post-MSCs treatment, evidenced by the elevation of neuroprotective Akkermansia and reduction of the AD-associated Sphingomonas. To examine whether gut microbiota involved in MSCs efficacy in treating AD, SHED with better anti-inflammatory and gut microbiota recovery effects among three MSCs, and another AD model 5 × FAD mice with earlier and more pathological proteins in brain than APP/PS1, were selected for further studies. Antibiotic-mediated gut microbial inactivation attenuated MSCs efficacy in 5 × FAD mice, implicating the involvement of gut microbiota in the therapeutic mechanism. Functional analysis of altered gut microbiota and targeted bile acid metabolism profiling revealed a significant enhancement in bile acid variety following MSCs therapy. A chief bile acid constituent, taurocholic acid (TCA), was orally administered to AD mice and similarly abated AD symptoms. Nonetheless, the disruption of intestinal neuronal integrity with enterotoxin abrogated the ameliorative impact of both MSCs and TCA treatments. Collectively, our findings substantiate that MSCs confer therapeutic benefits in AD within a paradigm that primarily involves regulation of gut microbiota and their metabolites through the MGBA.

Unveiling gut microbiota's role: Bidirectional regulation of drug transport for improved safety.

Drug safety is a paramount concern in the field of drug development, with researchers increasingly focusing on the bidirectional regulation of gut microbiota in this context. The gut microbiota plays a crucial role in maintaining drug safety. It can influence drug transport processes in the body through various mechanisms, thereby modulating their efficacy and toxicity. The main mechanisms include: (1) The gut microbiota directly interacts with drugs, altering their chemical structure to reduce toxicity and enhance efficacy, thereby impacting drug transport mechanisms, drugs can also change the structure and abundance of gut bacteria; (2) bidirectional regulation of intestinal barrier permeability by gut microbiota, promoting the absorption of nontoxic drugs and inhibiting the absorption of toxic components; (3) bidirectional regulation of the expression and activity of transport proteins by gut microbiota, selectively promoting the absorption of effective components or inhibiting the absorption of toxic components. This bidirectional regulatory role enables the gut microbiota to play a key role in maintaining drug balance in the body and reducing adverse reactions. Understanding these regulatory mechanisms sheds light on novel approaches to minimize toxic side effects, enhance drug efficacy, and ultimately improve drug safety. This review systematically examines the bidirectional regulation of gut microbiota in drug transportation from the aforementioned aspects, emphasizing their significance in ensuring drug safety. Furthermore, it offers a prospective outlook from the standpoint of enhancing therapeutic efficacy and reducing drug toxicity, underscoring the importance of further exploration in this research domain. It aims to provide more effective strategies for drug development and treatment.

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children

A preliminary examination of gut microbiota and emotion regulation in 2- to 6-year-old children