Structural elucidation of a Acanthopanax senticosus polysaccharide CQ-1 and its hepatoprotective activity via gut health regulation and antioxidative defense.

Acanthopanax senticosus has proven health benefits, particularly for liver damage. The objective of this study was to elucidate the protective effects and the underlying mechanisms of action of A. senticosus against metabolic dysfunction-associated fatty liver disease (MAFLD). A novel homogeneous water-soluble polysaccharide, CQ-1, was successfully isolated and purified from A. senticosus root. The main chain structure of CQ-1 was identified as →2)-α-L-Rha-(1 â†’ 4)-α-D-GalAp-(1 â†’ 6)-ß-D-Galp-(1→. Additionally, branched chains comprising an arabinosyl residue, galactosyl residue, and galacturonic acidic residue were identified as being attached to →2,4)-α-L-Rha-(1→, →3,6)-ß-D-Galp-(1→, and →3,4)-α-D-GalAp-(1→, respectively. CQ-1 exhibited antioxidant and prebiotic activities in vitro. CQ-1 increased antioxidant capacity and reduced serum pro-inflammatory cytokines in mice. Additionally, CQ-1 has been shown to enhance the diversity and composition of the gut microbiota, thereby facilitating the restoration of gut function. These include improving intestinal barrier function and increasing short-chain fatty acid levels in mice. Our study has shown that CQ-1 has a hepatoprotective effect in MAFLD mice, and we have proposed that CQ-1 may be a promising strategy for the treatment of MAFLD.

Human Amniotic Epithelial Stem Cells Promote Functional Recovery After Spinal Cord Injury In Rats By Regulating The Polarization Of Macrophages.

Spinal cord injury (SCI) is a catastrophic nerve injury caused by extremely severe damage to the spinal cord, for which effective treatments are currently unavailable. Human amniotic epithelial stem cells (hAESCs) are considered promising candidates for transplantation in various clinical and preclinical applications, due to their lack of limitations such as ethical barriers, immune rejection, tumorigenicity, or cell origin. Nevertheless, the effectiveness and mechanism by which hAESCs treat SCI remain elusive. To assess the motor function recovery process following SCI in rats, the Basso Beattie Bresnahan (BBB) behavior test, inclined plate scale and motor evoked potential (MEP) analysis were used in this study after transplantation of hAESCs at different doses. And the underlying mechanism was investigated by histological and molecular methods. The transplantation of hAESCs can significantly promote the recovery of motor function in SCI group, and the higher the dose, the better the effect. Compared with SCI group, hAESCs group had reduced tissue damage, significantly increased the number of neurons, neurofilaments and myelin sheath, and significantly reduced syringomyelia and glial scars. In addition, hAESCs inhibited the Levels of tumor necrosis factor (TNF-α) and interleukin-6 (IL-6) and increased the expression of the interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-13 (IL-13), and promoted the shift of M1-polarized macrophages to M2-polarized macrophages. Our results demonstrate that hAESCs promoted the recovery of motor function after SCI by promoting M2 polarization of macrophages and reducing neuroinflammation. These findings may provide novel therapeutic strategies for SCI.

Neurotoxicity and intestinal microbiota dysbiosis induced by per- and polyfluoroalkyl substances in crucian carp (Carassius auratus).

Per- and polyfluoroalkyl substances (PFAS) have been called "forever chemicals" due to their inherent chemical stability. Their potential toxic effects on aquatic animals and health risk assessments have not been fully elucidated. In this study, we investigated the toxic effects of PFASs at environmentally relevant concentrations (200 ng/L) on crucian carp (Carassius auratus). The results showed that PFAS reduced the comfort behaviour of crucian carp and was associated with reduced levels of acetylcholinesterase and dopamine in the brain. PFAS exposure also decreased the activities of total superoxide dismutase, catalase and glutathione peroxidase, while increasing the levels of malondialdehyde. PFAS caused over-expression of the pro-inflammatory cytokines TNF-α, IFN-γ and stress-related genes Caspase-3, HSP-70 in the fish brain. Pathological staining showed that PFAS caused multifocal demyelination and perineural vacuolization in brain, intestinal tissue also showed reduced villus length and focal damage. PFASs altered the composition of the gut microbiota of crucian carp, significantly increasing the abundance of potentially pathogenic bacteria and the potential pathogenicity of the microbiota. It is suggested that PFASs may cause varying degrees of tissue damage by destabilising the gut microbiota. These results provide insights for assessing the toxicity of PFAS contaminants at aquatic environmental concentrations.

A novel subtype classification and corresponding surgical strategies for spinal dural cysts -a report of 104 cases.

BACKGROUND: The nomenclature, classification, and surgical approaches for spinal dural cysts (SDCs) remain a subject of controversy. PURPOSE: The present study proposes a novel subtype classification system and corresponding surgical strategies, with the aim of enhancing comprehension of this entity and standardizing surgical treatment. STUDY DESIGN: A retrospective review. PATIENT SAMPLE: A total of 104 patients with SDCs underwent novel subtype classification and corresponding surgical strategies from January 2015 to December 2021. Fifty-four patients who underwent conventional surgery from January 2012 to December 2014 as the control group for preliminary validation. OUTCOME MEASURES: The outcomes are categorized into 4 levels: excellent, good, unchanged, and deteriorated, based on neurological improvement and pain relief. Grades of excellent and good were identified as improvements. Follow-up magnetic resonance imaging and complications were also evaluated. METHODS: Based on the shared pathogenic factor of dural defects, the dural-associated cysts in the spinal canal are uniformly referred to as SDCs. They are further classified into Type 1 (no nerve roots) and Type 2 (containing nerve roots), with 4 additional subtypes based on the shape of the leak and the flow of leakage. The fissure-shaped leak of Type 1a SDCs is directly sutured, whereas the aperture-shaped leak of Type 1b is repaired using a patch. Low-flow leakage of Type 2a is directly sealed using a combination of adipose tissue and fibrin glue, whereas high-flow Type 2b necessitates suturing at the end of the leak to attenuate cerebrospinal fluid flow prior to sealing. RESULTS: The follow-up period averaged 23.8 months. Excellent or good outcomes were achieved in 100%, 88.9%, 100%, and 97.3% for the 4 subtypes respectively. The overall improvement rate of SDCs was 97.1%, which was significantly higher than that of the conventional surgery group (85.2%, p=.008). MRI follow-up showed a significant reduction in cyst size of 100%, 100%, 97.8%, and 97.3% for the 4 subtypes, respectively. The primary complications included pseudomeningocele in 4 cases (3.8%) and delayed wound healing in 5 cases (4.8%). The complication rate was also significantly lower than that of the control group (8.7% vs 24.1%, p=.008). CONCLUSIONS: Subtyping SDCs based on the variation of leaks and leakage can enable more targeted surgical strategies, which are helpful for improving treatment effectiveness and reducing complications.

Pseudomonas putida HE alleviates glyphosate-induced toxicity in earthworm: Insights from the neurological, reproductive and immunological status.

The proceeding study aimed to isolate glyphosate-degrading bacteria from soil and determine optimal degradation conditions through single-factor experiments and response surface methodology. The detoxifying efficacy of the isolate on glyphosate was assessed using earthworm model. The results indicate that Pseudomonas putida HE exhibited the highest glyphosate degradation rate. Optimal conditions for glyphosate degradation were observed at an inoculation percentage of approximately 5%, a pH of 7, and a temperature of 30 °C. Glyphosate induced notable neurotoxicity and reproductive toxicity in earthworms, evidenced by reduced activity of the neurotoxicity-associated enzyme AChE. Additionally, an increase in the activities of catalase, superoxide dismutase, and lactate dehydrogenase was observed. H&E staining revealed structural disruptions in the earthworm clitellum, with notable atrophy in the structure of spermathecae. Furthermore, glyphosate activation of earthworm immune systems led to increased expression of immune-related genes, specifically coelomic cytolytic factor and lysozyme. Notably, the introduction of strain HE mitigated the glyphosate toxicity to the earthworms mentioned above. P. putida HE was able to increase soil enzyme activities that were reduced due to glyphosate. The isolate P. putida HE, emerged as an effective and cost-efficient remedy for glyphosate degradation and toxicity reduction in natural settings, showcasing potential applications in real ecological settings.

Dencichine attenuates the virulence of Fusobacterium nucleatum by targeting hydrogen sulfide-producing enzyme.

Oral opportunistic pathogen Fusobacterium nucleatum can participate in various disease processes through the metabolite hydrogen sulfide, such as halitosis and colorectal cancer. The object of this study is to identify inhibitor capable of suppressing Fn1220, which is the principal hydrogen sulfide-producing enzyme in F. nucleatum. Through this inhibition, we aim to reduce the hydrogen sulfide production of F. nucleatum, consequently diminishing its virulence. Employing molecular docking techniques for inhibitor screening, we identified dencichine as the monomeric compound from Chinese medicine exhibiting the lowest binding energy to Fn1220 among a set of 27,045 candidates, and evaluated in vitro the ability of dencichine to inhibit hydrogen sulfide production using bismuth chloride method. Additionally, we investigated its impact on key virulence factors, including biofilm formation, hemolysis, and adhesion factors of F. nucleatum, using the crystalline violet method, sheep blood method, and RT-qPCR, respectively. Furthermore, we assessed the influence of dencichine on the lifespan of Caenorhabditis elegans. Results showed that dencichine was a suitable inhibitor of the Fn1220 of F. nucleatum, which significantly inhibited the production of virulence factors, e.g., biofilm, hemolysin, FadA, and Fap2 of F. nucleatum and improved the survival of C. elegans. We successfully identified the inhibitor of the enzyme Fn1220, dencichine, which inhibited the production of hydrogen sulfide and attenuated the virulence of F. nucleatum and holds promise as a potential therapeutic avenue for addressing oral diseases, e.g., halitosis in the future.

Contralesional Anodal Transcranial Direct Current Stimulation Promotes Intact Corticospinal Tract Axonal Sprouting and Functional Recovery After Traumatic Brain Injury in Mice.

BACKGROUND: Anodal transcranial direct current stimulation (AtDCS), a neuromodulatory technique, has been applied to treat traumatic brain injury (TBI) in patients and was reported to promote functional improvement. We evaluated the effect of contralesional AtDCS on axonal sprouting of the intact corticospinal tract (CST) and the underlying mechanism in a TBI mouse model to provide more preclinical evidence for the use of AtDCS to treat TBI. METHODS: TBI was induced in mice by a contusion device. Then, the mice were subjected to contralesional AtDCS 5 days per week followed by a 2-day interval for 7 weeks. After AtDCS, motor function was evaluated by the irregular ladder walking, narrow beam walking, and open field tests. CST sprouting was assessed by anterograde and retrograde labeling of corticospinal neurons (CSNs), and the effect of AtDCS was further validated by pharmacogenetic inhibition of axonal sprouting using clozapine-N-oxide (CNO). RESULTS: TBI resulted in damage to the ipsilesional cortex, while the contralesional CST remained intact. AtDCS improved the skilled motor functions of the impaired hindlimb in TBI mice by promoting CST axon sprouting, specifically from the intact hemicord to the denervated hemicord. Furthermore, electrical stimulation of CSNs significantly increased the excitability of neurons and thus activated the mechanistic target of rapamycin (mTOR) pathway. CONCLUSIONS: Contralesional AtDCS improved skilled motor following TBI, partly by promoting axonal sprouting through increased neuronal activity and thus activation of the mTOR pathway.

Saccharomyces cerevisiae SC-2201 Attenuates AOM/DSS-Induced Colorectal Cancer by Modulating the Gut Microbiome and Blocking Proinflammatory Mediators.

Colorectal cancer is the third most common cancer in the world today, and studies have shown that the ratio of Candida to Saccharomyces cerevisiae increased, and the abundance of S. cerevisiae in the intestines of patients with colorectal cancer decreased, which suggests that there is an imbalance in the proportion of fungi in the intestines of patients with colorectal cancer. The objective of this study was to screen S. cerevisiae isolate from traditional Chinese fermentation starters and assess its ability to ameliorate dysbiosis and to alleviate the carcinogenic process of azoxymethane/dextran sodium sulfate-induced colorectal cancer in mice model. S. cerevisiae strain SC-2201 was isolated and exhibited probiotic properties, including the ability to survive in an acidic pH environment and in the presence of bile salts in the gastrointestinal tract, as well as antioxidant activities. Oral administration of S. cerevisiae SC-2201 not only alleviated weight loss but also reduced colonic shortening and histological damage in azoxymethane/dextran sodium sulfate-induced colorectal cancer in mice. Furthermore, the administration of S. cerevisiae SC-2201 suppressed the expression of proinflammatory mediators, such as interleukin-1ß, interleukin-6, cyclooxygenase-2, vascular endothelial growth factor, nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3. Specifically, the analysis of gut bacteriome showed a significant decrease in Bacteroidota and Campylobacterota levels, as well as an increase in Proteobacteria level in the colorectal cancer group, which was alleviated by supplementation with S. cerevisiae SC-2201. The analysis of the mycobiome revealed a significant increase in the levels of Basidiomycota, Apiosordaria, Naganishia, and Taphrina genera in the colorectal cancer group, which were alleviated after supplementation with S. cerevisiae SC-2201. However, the levels of Xenoramularia, Entoloma, and Keissleriella were significantly increased after administration with S. cerevisiae SC-2201. Overall, the findings of this study demonstrate that S. cerevisiae SC-2201 possesses potential probiotic properties and can effectively attenuate the development of colorectal cancer, highlighting its cancer-preventive potential. This is the first report of a S. cerevisiae strain isolated from traditional Chinese fermentation starters which showed good probiotic properties, and mitigated azoxymethane/dextran sodium sulfate-induced colorectal cancer by modulating the gut microbiome and blocking proinflammatory mediators in mice.

Ultrasmall Cu2O@His Nanozymes with RONS Scavenging Capability for Anti-inflammatory Therapy.

High concentrations of reactive oxygen and nitrogen species (RONS) are key characteristics of inflammatory sites. Scavenging RONS at the site of inflammation is an effective therapeutic strategy. This study introduces ultrasmall Cu2O@His nanoparticles with RONS-scavenging ability for the treatment of inflammatory bowel disease (IBD) in mice. The strong coordination between the nitrogen atom in histidine (His) and copper enhances the dispersion and stability of Cu2O@His. Due to their small size and large surface area, Cu2O@His exhibits outstanding RONS-clearing ability. Importantly, Cu2O@His can target mitochondrial sites and repair damaged mitochondria. With excellent dispersion and scavenging RONS ability, Cu2O@His demonstrates good efficacy in treating mouse IBD. This work provides a new paradigm for developing nanozymes with an ultrasmall size and multiple scavenging RONS abilities.

Alcohol degradation, learning, and memory-enhancing effect of Acetobacter pasteurianus BP2201 in Caenorhabditis elegans model.

AIMS: This study aimed to investigate the probiotic effects of Acetobacter pasteurianus BP2201, isolated from brewing mass, for the treatment of alcohol-induced learning and memory ability impairments in a Caenorhabditis elegans model. METHODS AND RESULTS: Acetobacter pasteurianus BP2201 was examined for probiotic properties, including acid and bile salt resistance, ethanol degradation, antioxidant efficacy, hemolytic activity, and susceptibility to antibiotics. The strain displayed robust acid and bile salt tolerance, efficient ethanol degradation, potent antioxidant activity, and susceptibility to specific antibiotics. Additionally, in the C. elegans model, administering A. pasteurianus BP2201 significantly improved alcohol-induced learning and memory impairments. CONCLUSIONS: Acetobacter pasteurianus BP2201 proves to be a promising candidate strain for the treatment of learning and memory impairments induced by alcohol intake.

Fusobacterium nucleatum and its metabolite hydrogen sulfide alter gut microbiota composition and autophagy process and promote colorectal cancer progression.

IMPORTANCE: Colorectal cancer (CRC) is the second most common cancer in the world; the main treatment for CRC is immunosuppressive therapy, but this therapy is only effective for a small percentage of CRC patients, so there is an urgent need for a treatment with fewer side effects and higher efficacy. This study demonstrated that Fusobacterium nucleatum with increased abundance in CRC can regulate the autophagy process and disrupt normal intestinal microbiota by producing hydrogen sulfide, factors that may be involved in the development and progression of CRC. This study may provide a reference for future CRC treatment options that are efficient and have fewer side effects.

Synthetic microbial consortia for the treatment of Clostridioides difficile infection in mice model.

Clostridioides difficile infection (CDI) as of recent has become a great concern to the impact on human health due to its high hazardous risk and rate of recurrence. Live bacterial therapeutics is a promising method to treat or prevent CDI. Here, a synthetic microbial consortia (SMC) B10 was constructed using probiotic strains with antibacterial and anti-quorum sensing activities, and the therapeutic effect of SMC B10 against C. difficile infection was evaluated in vitro. Compared to the model group, the treatment of SMC B10 significantly increased the survival rate. The clinical signs of mice were significantly ameliorated, especially the cecum injury, while the secretion of pro-inflammatory associated cytokines such as IL-1α, IL-6, IL-17A and TNF-α was reduced, the expression of TLR4 was inhibited, which alleviated the inflammatory response, and the expression of the tight junction protein Claudin-1 was increased, ultimately promoting the recovery of host health. The treatment of B10 restored gut microbiota dysbiosis and led to a healthy intestinal microbiota structure, significantly improved alpha diversity, suppressing potentially harmful bacteria and restoring other core bacterial species. In conclusion, SMC B10 can effectively treat CDI through modulate gut microbiota and attenuate the inflammatory response.

Acetobacter pasteurianus BP2201 alleviates alcohol-induced hepatic and neuro-toxicity and modulate gut microbiota in mice.

The excessive consumption of alcohol results in a dysbiosis of the gut microbiota, which subsequently impairs the gut microbiota-brain/liver axes and induces cognitive dysfunction and hepatic injury. This study aimed to investigate the potential effect of Acetobacter pasteurianus BP2201 in reducing the negative effects of alcohol consumption on cognitive function and liver health by modulating the gut microbiota-brain/liver axes. Treatment with A. pasteurianus BP2201 improved alcohol-induced hippocampal damage, suppressed neuroinflammation, promoted neuroprotein expression in the hippocampus and enhanced cognitive function. At the same time, A. pasteurianus BP2201 can also reduce serum lipid levels, relieve oxidative stress, inhibit TLR4/MyD88/NF-κB pathway, reduce the secretion of TNF-α and IL-1ß, so as to improve alcoholic liver injury. Concomitantly, the treatment with A. pasteurianus BP2201 leads to a shift in the intestinal microbiota structure towards that of healthy individuals, inhibiting the proliferation of harmful bacteria and promoting the recovery of beneficial bacteria. In addition, it also improves brain cognitive dysfunction and liver health by affecting the gut microbiota-brain/liver axes by promoting the synthesis of relevant amino acids and the metabolism of nucleotide base components. These findings demonstrate the potential of regulating the gut microbiome and gut microbiota-brain/liver axes to mitigate alcohol-induced disease.

Characterization of Cetobacterium somerae CPU-CS01 isolated from the intestine of healthy crucian carp (Carassius auratus) as potential probiotics against Aeromonas hydrophila infection.

Cetobacterium somerae is a commensal bacterium for many fish species. However, research on C. somerae has been limited so far, and its function and beneficial potential require to be further investigated. The objective of this study was to evaluate the probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp (Carassius auratus). Hemolytic activity, antibiotic susceptibility, acid tolerance, bile salt tolerance, free radical scavenging, and enzyme production properties were tested for in vitro. Caenorhabditis elegans and zebrafish (Danio rerio) model were used to evaluate the antioxidant and anti-infective effects of C. somerae CPU-CS01 in vivo. Our results showed that C. somerae CPU-CS01 had no hemolytic activity, it produced cellulase, amylase, and survived at low pH (2.0-3.0) and in the presence of bile salts. The cell-free culture supernatant (CFCS) of C. somerae CPU-CS01 possessed DPPH radical, hydroxyl radical, and superoxide anion scavenging activity. C. elegans fed with C. somerae CPU-CS01 were more resistant to hydrogen peroxide-induced oxidative stress and Aeromonas hydrophila infection. In addition, zebrafish-fed diets containing C. somerae CPU-CS01 showed improved survival after A. hydrophila infection. Based on these results, the positive probiotic properties of C. somerae CPU-CS01 isolated from the intestinal contents of crucian carp make it a potential candidate for probiotic.

Synthetic bacterial consortia transplantation for the treatment of Gardnerella vaginalis-induced bacterial vaginosis in mice.

Bacterial vaginosis (BV) is a disease caused by vaginal microbiota dysbiosis. Here, we propose the use of synthetic bacterial consortia transplantation (SBCT) for the treatment of Gardnerella vaginalis-induced BV mice. The results showed that SBCT significantly reduced vaginal tissue damage and restored the vaginal microbiota, decreased the secretion of pro-inflammatory cytokines (IL-1ß and IL-8), and suppressed NF-κB activation. IL-17, iNOS, and COX-2 expression in vaginal tissue were also down-regulated. However, IL-10 and Foxp3 showed up-regulated expression in mice. Compared with vaginal microbiota transplantation (VMT), results indicated that VMT was more effective than SBCT in suppressing G. vaginalis-induced inflammation. The obtained results suggest that synthetic bacterial consortia might be used as a potential biotherapeutic agent for the treatment of G. vaginalis-induced bacterial vaginosis. Video Abstract.

Lactobacillus salivarius CPU-01 Ameliorates Temozolomide-Induced Intestinal Mucositis by Modulating Gut Microbiota, Maintaining Intestinal Barrier, and Blocking Pro-inflammatory Cytokines.

Chemotherapy-induced intestinal mucositis is one of the major toxic side effects in the treatment of cancer patients. The purpose of this study is to screen lactic acid bacteria which could alleviate intestinal inflammation and damage induced by chemotherapeutic agents and explore the possible underlying mechanisms. Lactobacillus salivarius CPU-01 was selected from traditional Chinese fermented foods due to its protective effects on the toxicity of temozolomide in Caenorhabditis elegans. Eighteen ICR mice were randomly divided into 3 groups including control group, temozolomide-induced intestinal mucositis group, and temozolomide + L. salivarius CPU-01 group, and were used to investigate the effect of L. salivarius CPU-01 on chemotherapy-induced intestinal mucositis. It has been demonstrated that the administration of L. salivarius CPU-01 can prevent colon shortening and alleviate colon tissue damage caused by temozolomide-induced intestinal mucositis in mice. L. salivarius CPU-01 relieved the intestinal microbiota disorders caused by temozolomide and contributed to the growth of beneficial bacteria, such as Lactobacillus, Clostridia UCG - 014_norank, and Akkermansia. In vivo experiments also indicated that L. salivarius CPU-01 can suppress the level of temozolomide-induced pro-inflammatory cytokines in serum and mRNA expression in the small intestine tissues. It was also found that L. salivarius CPU-01 significantly increased the expressions of intestinal tight junction (TJ) proteins, ZO-1, and Occludin proteins in mice treated with temozolomide. These findings suggest that L. salivarius CPU-01 can ameliorate temozolomide-induced intestinal mucositis by modulating gut microbiota, blocking pro-inflammatory cytokines, and repairing the intestinal barrier. These findings suggest probiotics may serve as a potential alternative therapeutic strategy for the prevention of chemotherapy-induced intestinal mucositis in the future.

ß-sitosterol inhibits trimethylamine production by regulating the gut microbiota and attenuates atherosclerosis in ApoE-/- mice.

The intestinal microbial metabolite trimethylamine (TMA), which is activated by flavin monooxygenase (FMO) to produce trimethylamine-N-oxide (TMAO), has been implicated in the pathogenesis of atherosclerosis (AS), leading to the development of therapeutic strategies for AS. This study aimed to investigate whether ß-sitosterol can inhibit TMA production in ApoE-/- mice by reshaping the gut microbial structure. 16S rRNA sequencing of the gut microbiota showed that ß-sitosterol has beneficial effects on intestinal flora function, especially the inhibition of bacteria genera that contain the gene cholintrimethylamine lyase, which is responsible for the major pathway for TMA production. In parallel, ß-sitosterol effectively reduced the TMA, FMO3, and TMAO levels while ameliorating the atherosclerotic plaques of AS mice. Moreover, ß-sitosterol could alleviate cholesterol metabolism and the inflammatory response, and improve the antioxidant defense capacity. These studies offer new insights into the mechanisms responsible for the antiatherosclerotic effects of ß-sitosterol, which targets the microbiota-metabolism-immunity axis as a possible therapy for AS.

Gypenoside XLIX Ameliorate High-Fat Diet-Induced Atherosclerosis via Regulating Intestinal Microbiota, Alleviating Inflammatory Response and Restraining Oxidative Stress in ApoE-/- Mice.

A high-fat choline diet (HFCD)-induced atherosclerosis model in ApoE-/- mice was established to explore the anti-atherosclerotic effects of gypenoside XLIX (GPE). It was found that HFCD-induced atherosclerotic index such as dyslipidemia, atherosclerotic plaque, inflammation, and gut microbiota dysfunction could be reduced by GPE treatment. GPE treatment could decrease Verrucomicrobia, Proteobacteria, and Actinobacteria abundance, and increase Firmicutes and Bacteroidetes population. Moreover, the Firmicutes/Bacteroidetes ratio increased significantly after treatment with GPE. After treatment with GPE, the relative abundance of trimethylamine-producing intestinal bacteria Clostridioides and Desulfovibrionaceae decreased while butyrate-producing bacteria such as Eubacterium, Roseburia, Bifidobacterium, Lactobacillus, and Prevotella increased significantly. The GPE group demonstrated higher SCFAs concentrations in the fecal sample, such as Acetic Acid, Propionic Acid, and Butyric Acid. Further pathway analysis showed that 29 metabolic pathways were appreciably disturbed during GPE treatment, including citrate cycle (TCA cycle); galactose and glycero-lipid-metabolism biosynthesis of unsaturated fatty acids, fatty acid biosynthesis. This study suggests that the anti-atherosclerotic effect of GPE is related to the substantial changes in intestinal microbiota and anti-inflammatory activity.

Synthesis and Evaluation of Antioxidant and Potential Prebiotic Activities of Acetylated and Butyrylated Fructo-Oligosaccharides.

Fructo-oligosaccharides (FOS) have well-known bifidogenic effects as probiotics. In this study, esterification was adopted for FOS modification to produce better prebiotic properties. We synthesized and characterized acetylated fructo-oligosaccharides (Ac-FOS) and butyrylated fructo-oligosaccharides (Bu-FOS) as candidate prebiotics. Antioxidant activity and prebiotic esactiviti were evaluated as important indicators. We found, surprisingly, that butyrylation was an effective method in significantly improving the antioxidant activity of FOS. The fermentation products of feces from mice added to Ac-FOS and Bu-FOS, were investigated in vitro, including changes of pH values, short-chain fatty acids (SCFAs) production, and microbiota composition. Supplementation of Ac-FOS or Bu-FOS increased pH values and promoted the growth and activity of beneficial intestinal bacteria, such as Bifidobacteria and Lactobacillus. More importantly, the levels of prebiotic SCFAs were obviously elevated as detected by Gas Chromatography-Mass Spectrometry (GC-MS). Results suggest that Ac-FOS and Bu-FOS have great potential applications in SCFA delivery systems and gut microbiota regulation.

Gut Microbiota and Inflammatory Cytokine Changes in Patients with Ankylosing Spondylitis.

Ankylosing spondylitis (AS) is a chronic inflammatory disease characterized by sacroiliac joint lesions and spinal ascending involvement. The aim of this work was at investigating the gut microbiota profile and proinflammatory cytokines in AS patients. Gut microbiota of AS patients was clearly different from that of healthy human controls. 16S rRNA sequencing analysis demonstrated a changed microbial diversity in the AS patients, and there was a significant increase in the abundance of Cyanobacteria, Deinococcota, Patescibacteria, Actinobacteriota, and Synergistota at a phyla level increased in AS, while the relative abundance of Acidobacteriota, Bdellovibrionota, Campylobacterota, Chloroflexi, Gemmatimonadota, Myxococcota, Nitrospirota, Proteobacteria, and Verrucomicrobiota declined in AS patients. ELISA results for the markers of inflammation in the AS patients revealed increased concentrations of proinflammatory cytokines such as IL-23, IL-17, and IFN-γ. Our findings support the fact that the intestinal microbiota are altered in AS with an inflammatory status, which indicates that gut microbiota should be a potential target for ankylosing spondylitis therapy.