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Acta Pharmaceutica Sinica. B Mar 2023Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of C. A. , F. E. ex var. , ex ,...
Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injury increasing the gut microbiota and regulating macrophage anti-inflammatory activity in mice.
Sepsis-induced liver injury (SILI) is an important cause of septicemia deaths. BaWeiBaiDuSan (BWBDS) was extracted from a formula of C. A. , F. E. ex var. , ex , Thunb., Linn., Vas, (Jacq.) A. DC., and . Herein, we investigated whether the BWBDS treatment could reverse SILI by the mechanism of modulating gut microbiota. BWBDS protected mice against SILI, which was associated with promoting macrophage anti-inflammatory activity and enhancing intestinal integrity. BWBDS selectively promoted the growth of in cecal ligation and puncture treated mice. Fecal microbiota transplantation treatment indicated that gut bacteria correlated with sepsis and was required for BWBDS anti-sepsis effects. Notably, significantly reduced SILI by promoting macrophage anti-inflammatory activity, increasing interleukin-10 M2 macrophage production and enhancing intestinal integrity. Furthermore, heat inactivation (HI-) treatment promoted macrophage anti-inflammatory activity and alleviated SILI. Our findings revealed BWBDS and gut microbiota as novel prebiotic and probiotic that may be used to treat SILI. The potential underlying mechanism was at least in part, -dependent immune regulation and interleukin-10 M2 macrophage production.
PubMed: 36970196
DOI: 10.1016/j.apsb.2022.10.016 -
Gut Microbes 2022Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and...
Imbalance of gut microbiota homeostasis is related to the occurrence of ulcerative colitis (UC), and probiotics are thought to modulate immune microenvironment and repair barrier function. Here, in order to reveal the interaction between UC and gut microbiota, we screened a new probiotic strain by 16S rRNA sequencing from Dextran Sulfate Sodium (DSS)-induced colitis mice, and explored the mechanism and clinical relevance. (), as a potential anti-inflammatory bacterium was decreased colonization in colitis mice. Gavage could alleviate colitis by specifically increasing the proportion of intestinal macrophages and the secretion of Il-10 with macrophages depleted model and in mice. We identified this subset of immune cells activated as CD206 macrophages. Mechanistically, supplementation enhanced the mobilization of CD206 macrophages through the activation of STAT3 and . In addition, we revealed that TLR1/2 was essential for the activation of STAT3 and the recognition of by macrophages. Clinically, there was positive correlation between the abundance of and the expression level of and in UC tissues. could activate native macrophages into CD206 macrophages and release IL-10 through TLR1/2-STAT3 pathway to relieve experimental colitis. may serve as an immunomodulator and anti-inflammatory therapeutic target for UC.
Topics: Animals; Mice; Anti-Inflammatory Agents; Colitis; Colitis, Ulcerative; Dextran Sulfate; Gastrointestinal Microbiome; Interleukin-10; Lactobacillus johnsonii; Macrophages; RNA, Ribosomal, 16S; Toll-Like Receptor 1
PubMed: 36398889
DOI: 10.1080/19490976.2022.2145843 -
Frontiers in Endocrinology 2022Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Type 1 diabetes mellitus (T1DM) is characterized by autoimmune destruction of pancreatic β cells. Previous study has discovered that probiotic strains residing in the gut play essential roles in host immune regulation. However, few clinical results demonstrated probiotic would actually benefit in attenuating glycated hemoglobin (HbA1c) along with inflammatory cytokine levels of the T1DM patients and analyzed their gut microbiota profile at the same time. In this clinical trial, we evaluated the therapeutic efficacy of probiotics on HbA1c along with inflammatory cytokine levels of T1DM patients to determine an alternative administration mode for T1DM medication. The probiotics changed T1DM gut microbiota profile will be measured by next-generation sequencing (NGS).
RESEARCH DESIGN AND METHODS
A randomized, double-blind, placebo-controlled trial was performed at China Medical University Hospital. T1DM patients between 6 and 18 years of age were enrolled. 27 patients were administered regular insulin therapy plus capsules containing probiotic strains subsp. AP-32, MH-68, and subsp. CP-9 daily for 6 months, and 29 patients were administered insulin therapy without extra probiotic supplement as placebo group. The variations of fasting blood glucose and HbA1c in these patients were analyzed. In addition, serum levels of inflammatory cytokines and anti-inflammatory cytokine were assessed using enzyme-linked immunosorbent assay. Patients' stool microbiota were all subjects to NGS analysis.
RESULTS
NGS data showed elevated populations of and in the gut of patients with T1DM who were taking probiotics. Patients with T1DM who were administered probiotics showed significantly reduced fasting blood glucose levels compared with the before-intervention levels. The HbA1c levels of the patients also improved after administration of probiotics. The concentrations of IL-8, IL-17, MIP-1β, RANTES, and TNF-α were significantly reduced and were associated with an increased TGF-β1 expression after probiotic intervention. The persistence effect of glycemic control and immunomodulation were observed even 3 months after discontinuation of the probiotics.
CONCLUSIONS
Here, we found that conventional insulin therapy plus probiotics supplementation attenuated T1DM symptoms than receiving insulin treatment only. Probiotics supplementation with insulin treatment changed gut microbiota and revealed better outcome in stabilizing glycemic levels and reducing HbA1c levels in patients with T1DM through beneficial regulation of immune cytokines.
CLINICAL TRIAL REGISTRATION
ClinicalTrials.gov, identifier NCT03880760.
Topics: Bifidobacterium animalis; Blood Glucose; Cytokines; Diabetes Mellitus, Type 1; Glycated Hemoglobin; Humans; Insulin; Ligilactobacillus salivarius; Probiotics
PubMed: 35299968
DOI: 10.3389/fendo.2022.754401 -
Microorganisms Oct 2023has been used as a probiotic for decades to treat a wide range of illnesses, and has been found to have specific advantages in the treatment of a number of ailments. We... (Review)
Review
has been used as a probiotic for decades to treat a wide range of illnesses, and has been found to have specific advantages in the treatment of a number of ailments. We reviewed the potential therapeutic effects and mechanisms of in various diseases based on PubMed and the Web of Science databases. We obtained the information of 149 from NCBI (as of 14 February 2023), and reviewed their comprehensive metadata, including information about the plasmids they contain. This review provides a basic characterization of different and some of their potential therapeutic properties for various ailments. Although the mechanisms are not fully understood yet, it is hoped that they may provide some evidence for future studies. Furthermore, the antibiotic resistance of the various strains of is not clear, and more complete and in-depth studies are needed. In summary, presents significant research potential for the treatment or prevention of disease; however, more proof is required to justify its therapeutic application. An additional study on the antibiotic resistance genes it contains is also needed to reduce the antimicrobial resistance dissemination.
PubMed: 37894238
DOI: 10.3390/microorganisms11102580 -
The Journal of Experimental Medicine Nov 2021Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial...
Development of the immune system can be influenced by diverse extrinsic and intrinsic factors that influence the risk of disease. Severe early life respiratory syncytial virus (RSV) infection is associated with persistent immune alterations. Previously, our group had shown that adult mice orally supplemented with Lactobacillus johnsonii exhibited decreased airway immunopathology following RSV infection. Here, we demonstrate that offspring of mice supplemented with L. johnsonii exhibit reduced airway mucus and Th2 cell-mediated response to RSV infection. Maternal supplementation resulted in a consistent gut microbiome in mothers and their offspring. Importantly, supplemented maternal plasma and breastmilk, and offspring plasma, exhibited decreased inflammatory metabolites. Cross-fostering studies showed that prenatal Lactobacillus exposure led to decreased Th2 cytokines and lung inflammation following RSV infection, while postnatal Lactobacillus exposure diminished goblet cell hypertrophy and mucus production in the lung in response to airway infection. These studies demonstrate that Lactobacillus modulation of the maternal microbiome and associated metabolic reprogramming enhance airway protection against RSV in neonates.
Topics: Animals; Cytokines; Disease Models, Animal; Female; Gastrointestinal Microbiome; Lung; Mice; Mice, Inbred BALB C; Pregnancy; Respiratory Syncytial Virus Infections; Th2 Cells
PubMed: 34613328
DOI: 10.1084/jem.20210235 -
Journal of Translational Medicine Jan 2023Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and...
BACKGROUND
Necrotizing enterocolitis (NEC) is a devastating gastrointestinal disease with high morbidity and mortality, affecting preterm infants especially those with very low and extremely low birth weight. β-glucan has manifested multiple biological effects including anti-inflammatory, regulation of gut microbiota, and immunomodulatory activities. This study aimed to investigate the effects of β-glucan on NEC.
METHODS
Neonatal C57BL/6 mice were randomly divided into three groups: Control group, NEC group and β-glucan group. Newborn 3-day-old mice were gavaged with either 1 mg/ml β-glucan or phosphate buffer saline at 0.03 ml/g for 7 consecutive days before NEC induction and a NEC model was established with hypoxia combined with cold exposure and formula feeding. All the pups were killed after 72-h modeling. Hematoxylin-eosin staining was performed to assess the pathological injury to the intestines. The mRNA expression levels of inflammatory factors in intestinal tissues were determined using quantitative real-time PCR. The protein levels of TLR4, NF-κB and tight junction proteins in intestinal tissues were evaluated using western blotting and immunohistochemistry. 16S rRNA sequencing was performed to determine the structure of the gut microbiota.
RESULTS
β-glucan administration ameliorated intestinal injury of NEC mice; reduced the intestinal expression of TLR4, NF-κB, IL-1β, IL-6, and TNF-α; increased the intestinal expression of IL-10; and improved the expression of ZO-1, Occludin and Claudin-1 within the intestinal barrier. Pre-treatment with β-glucan also increased the proportion of Actinobacteria, Clostridium butyricum, Lactobacillus johnsonii, Lactobacillus murinus, and Lachnospiraceae bacterium mt14 and reduced the proportion of Klebsiella oxytoca g Klebsiella in the NEC model.
CONCLUSION
β-glucan intervention prevents against NEC in neonatal mice, possibly by suppressing the TLR4-NF-κB signaling pathway, improving intestinal barrier function, and partially regulating intestinal microbiota.
Topics: Infant, Newborn; Humans; Animals; Mice; Animals, Newborn; NF-kappa B; Gastrointestinal Microbiome; Toll-Like Receptor 4; Enterocolitis, Necrotizing; RNA, Ribosomal, 16S; Infant, Premature; Mice, Inbred C57BL; Inflammation; Disease Models, Animal; Intestinal Mucosa
PubMed: 36627673
DOI: 10.1186/s12967-022-03866-x -
Pharmaceutics Dec 2023Methicillin-resistant biofilm-forming spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated...
Methicillin-resistant biofilm-forming spp. are found in about 25% of the overall cases of chronic wounds, which can undergo malignant degeneration and be associated with skin cancer. Although antimicrobial agents are clinically used to counteract pathogens and promote wound healing, they are increasingly ineffective against multi-drug resistant bacteria. Moreover, they can induce dysbiosis, which favors opportunistic pathogen infections and alters immune responses. Consequently, research on pathogen containment strategies is crucial. We aimed to evaluate the potential beneficial effect of LJO02 cell-free supernatant (CFS) and vitamin D, as single treatments or in combination, on cell viability, wound healing, and the pro-inflammatory interleukin-6 (IL-6) production of a -infected human immortalized keratinocyte cell line (HaCaT) in vitro model. The analysis showed that LJO02 CFS 20% / ratio and 100 nM vitamin D promoted infected cell viability and wound healing and significantly reduced IL-6 production. However, their effect was not synergic, since no significant difference between the single and combined treatments was observed. LJO02 CFS topic application and vitamin D supplementation could provide a valuable strategy for attenuating -induced pathogenesis, promoting wound healing and opening new therapeutic strategies supporting the conventional approaches.
PubMed: 38276496
DOI: 10.3390/pharmaceutics16010018 -
Frontiers in Nutrition 2021Obesity is considered a primary contributing factor in the development of many diseases, including cancer, diabetes, and cardiovascular illnesses. Phytochemical-rich...
Obesity is considered a primary contributing factor in the development of many diseases, including cancer, diabetes, and cardiovascular illnesses. Phytochemical-rich foods, associated to healthy gastrointestinal microbiota, have been shown to reduce obesity and associated comorbidities. In the present article, we describe the effects of the probiotic N6.2 and blueberry extracts (BB) on the gut microbiota and lipid profile of rats under a high-fat (HF) or low-calorie (LC) diet. was found to increase the levels of long chain fatty acids (LCFA) in the serum of all animals under HF diet, while reduced LCFA concentrations were observed in the adipose tissue of animals under HF diet supplemented with BB extracts. All animals under HF diet also showed lower protein levels of SREBP1 and SCAP when treated with . The gut microbiota diversity, β-diversity was significantly changed by in the presence of BB. A significant reduction in α-diversity was observed in the ileum of animals under HF diet supplemented with and BB, while increased α-diversity was observed in the ilium of animals under LC diet supplemented with or BB. In summary, and BB supplementation induced significant changes in gut microbiota diversity and lipid metabolism. The phospholipids pool was the lipidome component directly affected by the interventions. The ileum and colon microbiota showed clear differences depending on the diet and the treatments examined.
PubMed: 34722616
DOI: 10.3389/fnut.2021.757256 -
Metabolites Sep 2023Parenteral nutrition (PN), a vital therapy for patients with intestinal failure, can lead to the development of parenteral nutrition-associated liver disease (PNALD). In...
Parenteral nutrition (PN), a vital therapy for patients with intestinal failure, can lead to the development of parenteral nutrition-associated liver disease (PNALD). In this study, we aimed to investigate the role of () in a rat model of PNALD. Total parenteral nutrition (TPN)-fed rats were used to assess the role of in liver steatosis, bile acid metabolism, gut microbiota, and hepatocyte apoptosis. We observed a depletion of that was negatively correlated with the accumulation of glycochenodeoxycholic acid (GCDCA), a known apoptosis inducer, in rats subjected to TPN. attenuated TPN-induced liver steatosis by inhibiting fatty acid synthesis and promoting fatty acid oxidation. TPN resulted in a decrease in bile acid synthesis and biliary bile secretion, which were partially restored by treatment. The gut microbial profile revealed depletion of pathogenic bacteria in -treated rats. treatment reduced both hepatic GCDCA levels and hepatocyte apoptosis compared with the TPN group. In vitro, treatment inhibited GCDCA-induced hepatocyte apoptosis via its bile salt hydrolase (BSH) activity. Our findings suggest that protects against liver steatosis, bile acid dysregulation, and hepatocyte apoptosis in TPN-fed rats.
PubMed: 37887368
DOI: 10.3390/metabo13101043 -
Animal Nutrition (Zhongguo Xu Mu Shou... Dec 2023Developing effective strategies to prevent diarrhea and associated-gut disorders in mammals has gained great significance. Owing to the many health benefits provided by...
Developing effective strategies to prevent diarrhea and associated-gut disorders in mammals has gained great significance. Owing to the many health benefits provided by the commensal microbiota of the intestinal tract, such as against environmental perturbation, we explored the host phenotype-associated microbes and their probiotic potential. Based on the observations that the chronic heat stress-exposed weaned piglets present as heat stress-susceptible (HS-SUS) or heat stress-resistant (HS-RES) individuals, we confirmed the phenotypic difference between the two on growth performance ( < 0.05), diarrhea index ( < 0.001), intestinal heat shock protein 70 (HSP70) regulation ( < 0.01), and inflammatory responses ( < 0.01). By comparing the gut microbiome using 16S rRNA gene sequencing and KEGG functional analysis, we found that exhibited significantly higher relative abundance in the HS-RES piglets than in the HS-SUS ones ( < 0.05). Further experiments using a mouse model for chemical-induced inflammation and intestinal injury demonstrated that oral administration of a representative N5 (isolated from the HS-RES piglets) ameliorated the clinical and histological signs of colitis while suppressing intestinal pro-inflammatory cytokines TNF-α and IL-6 production ( < 0.05). We found that N5 treatment enhanced tight junction proteins ZO-1 and occludin and cytoprotective HSP70 levels under physiological condition and restored their mucosal expressions in colitis ( < 0.05). In support of the high production of the anti-inflammatory cytokine IL-10, N5 promoted the intestinal Peyer's patches MHCII and CD103 dendritic cell populations ( < 0.05), increased the regulatory T (Treg) cell numbers ( < 0.05), and decreased the Th17 population and its IL-17a production under physiological condition and during colitis ( < 0.01). Our results shed light on understanding the interaction between commensal and the host health, and provide N5 as an alternative to antibiotics for preventing diarrhea and intestinal diseases.
PubMed: 38033603
DOI: 10.1016/j.aninu.2023.04.012