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Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

ABSTRACT: Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J mice, we evaluated RCJ's protective role in DSS-induced colitis through two cycles of 3% DSS. Mice were daily gavaged with PBS or RCJ until the endpoint, and gut microbiota composition was analyzed via shotgun metagenomics. RCJ treatment significantly improved body weight (p ≤ 0.001), survival in mice (p < 0.001) and reduced disease activity index (DAI) scores. Further, RCJ improved colonic barrier integrity by enhancing the expression of protective colonic mucins (p < 0.001) and tight junction proteins (p ≤ 0.01) in RCJ + DSS-treated mice compared to the DSS group. Shotgun metagenomic analysis revealed an enrichment of short-chain fatty acids (SCFAs)-producing bacteria (p < 0.05), leading to increased Peroxisome Proliferator-Activated Receptor Gamma (PPAR-γ) activation (p ≤ 0.001). This, in turn, resulted in repression of the nuclear factor κB (NFκB) signaling pathway, causing decreased production of inflammatory cytokines and chemokines. Our study demonstrates colitis remission in a DSS-induced mouse model, showcasing RCJ as a potential modulator for gut microbiota and metabolites, with promising implications for IBD prevention and treatment.

SUBMITTER: Jean Wilson E

PROVIDER: S-EPMC10778654 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

Jean Wilson Emily E Sirpu Natesh Nagabhishek N Ghadermazi Parsa P Pothuraju Ramesh R Prajapati Dipakkumar R DR Pandey Sanjit S Kaifi Jussuf T JT Dodam John R JR Bryan Jeffrey N JN Lorson Christian L CL Watrelot Aude A AA Foster Jason M JM Mansell Thomas J TJ Joshua Chan Siu Hung SH Batra Surinder K SK Subbiah Jeyamkondan J Rachagani Satyanarayana S

International journal of molecular sciences 20231230 1

Gut microbiota plays a crucial role in inflammatory bowel diseases (IBD) and can potentially prevent IBD through microbial-derived metabolites, making it a promising therapeutic avenue. Recent evidence suggests that despite an unclear underlying mechanism, red cabbage juice (RCJ) alleviates Dextran Sodium Sulfate (DSS)-induced colitis in mice. Thus, the study aims to unravel the molecular mechanism by which RCJ modulates the gut microbiota to alleviate DSS-induced colitis in mice. Using C57BL/6J ...[more]

PMID: 38203712

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Project description:BackgroundFibrotic liver injury is a progressive scarring event, which may permanently affect liver function and progress into devastating end-stage liver diseases due to the absence of effective therapies. Si-Wu-Tang (SWT), a traditional Chinese medicine formula used in clinic to treat gynecological disorders for centuries, has been investigated in recent preliminary findings for its role in alleviating chronic liver diseases. Here we aim to elucidate the therapeutic effects and possible mechanisms of SWT against fibrotic liver injury.MethodsUHPLC-MS/MS was performed to investigate the chemical characterization of SWT. After intragastrically administered with carbon tetrachloride (CCl4) every 3 days for 1-week, C57BL/6 mice were orally administered with SWT (5.2, 10.4 and 20.8 g/kg) once daily for 3 weeks along with CCl4 challenge. Liver function was determined by the measurement of serum biomarkers, hematoxylin and eosin (H&E) and Masson's trichrome staining. Intestinal inflammatory infiltration and the disruption of intestinal barrier were examined by H&E and E-cadherin immunohistochemical staining. The microbial composition of intestinal content was determined by 16S rRNA sequencing. Serum bile acids (BAs) profiling was analyzed by LC-MS/MS. Simultaneously, the expression of genes of interest was determined by qPCR and western blot.ResultsSWT exhibited remarkable therapeutic effects on CCl4-induced liver fibrosis, as indicated by improved collagen accumulation in livers, intestinal barrier injury and hepatic and intestinal inflammatory response. Results of 16S rRNA sequencing revealed that SWT treatment strikingly restructured intestinal microbiota in fibrotic mice by increasing the relative abundances of Bacteroides and Lachnoclostridium and decreasing the relative abundances of Alistipes and Rikenellaceae. UHPLC-MS/MS data suggested that SWT altered the composition of BAs in circulation as evidenced by increased unconjugated BAs like cholic acid and chenodeoxycholic acid but decreased conjugated BAs including taurocholic acid and taurodeoxycholic acid, compared to that in CCl4 mice. Notably, SWT efficiently improved the imbalance of BA homeostasis in livers caused by CCl4 via activating farnesoid X receptor (FXR)-fibroblast growth factor 15 enterohepatic and FXR-small heterodimer partner hepatic pathways.ConclusionSWT decreased inflammatory response, reconstructed gut microbiota-mediated BA homeostasis as well as activated FXR pathways, which eventually protected against CCl4-induced fibrotic liver injury.

Project description:Ulcerative colitis (UC) is a complex chronic pathological condition of the gut in which microbiota targeted treatment, such as fecal microbiota transplantation (FMT), has shown an encouraging effect. The aim of the present study was to investigate the efficacy and safety of FMT in patients with mild or moderate UC. A single-center, open-label study was designed, including 47 patients with mild or moderate active UC who received three treatments of fresh FMT via colonic transendoscopic enteral tubing within 1 week. The inflammatory bowel disease questionnaire, partial Mayo scores, colonoscopy, erythrocyte sedimentation rate, C-reactive protein level and procalcitoin values were used to assess the efficacy of FMT and alteration in gut microbiota was detected by 16S ribosomal RNA-sequencing. Before FMT, microbiota Faecalibacterium prausnitzii (F. prausnitzii) levels were significantly decreased in patients with UC compared with healthy donors (P<0.01). At 4 weeks post-FMT, F. prausnitzii levels were significantly increased (P<0.05), and the Mayo score was significantly decreased (1.91±1.07 at baseline vs. 4.02±1.47 at week 4; P<0.001) in patients with UC compared with healthy donors. Steroid-free clinical responses were reported in 37 patients (84.1%), and steroid-free clinical remission was achieved in 31 patients (70.5%) at week 4 post-FMT, however, steroid-free remission was not achieved in any patient. No adverse events were reported in 41 (93.2%) patients after FMT or during the 12-week follow-up. Shannon's diversity index and Chao1 estimator were also improved in patients with UC receiving FMT. In conclusion, the results of the present study suggested that FMT resulted in clinical remission in patients with mild to moderate UC, and that the remission may be associated with significant alterations to the intestinal microbiota of patients with UC. Furthermore, F. prausnitzii may serve as a diagnostic and therapeutic biomarker for the use of FMT in UC.

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Project description:BackgroundAntimicrobials are often used to prevent and treat diarrhea induced by enteroaggregative Escherichia coli (EAEC) in young ruminants. However, drug overuse or misuse accelerates the spread of multidrug-resistant extended-spectrum β-lactamase (ESBL)-producing E. coli. Thus, supplementary foods as alternatives to antibiotics are needed to prevent colibacillus diarrhea in neonatal dairy calves. Ursodeoxycholic acid (UDCA), a therapeutic bile acid, helps alleviate colitis. However, how UDCA helps alleviate ESBL-EAEC-induced clinical symptoms and colitis remains unclear.ResultsWe investigated the microbial profiles and metabolites of healthy and diarrheic neonatal calves to determine microbial and metabolite biomarkers in early-life development. Both the gut microbiota communities and their associated metabolites differed between healthy and diarrheic calves. Commensal Butyricicoccus, Faecalibacterium, Ruminococcus, Collinsella, and Coriobacterium were key microbial markers that distinguished healthy and diarrheic gut microbiomes. Random forest machine-learning algorithm and Spearman correlation results indicated that enriched UDCA, short-chain fatty acids (SCFAs), and other prebiotics were strongly positively correlated with these five bacterial genera. We explored the effect of ursodiol on bacterial growth, cell adherence, and lipopolysaccharide-treated Caco-2 cells. Adding ursodiol induced direct antibacterial effects, suppressed proinflammatory effects, and reduced cell integrity damage. Oral ursodiol delivery to neonatal mice exhibited significant antibacterial effects and helped maintain colonic barrier integrity in mouse models of peritonitis sepsis and oral infection. UDCA supplementation attenuated colitis and recovered colonic SCFA production. To validate this, we performed fecal microbiota transplantations to inoculate ESBL-EAEC-infected neonatal mice. Microbiotas from UDCA-treated neonatal mice ameliorated colitis and hindgut commensal bacterial damage compared with that of the microbiotas from the control and placebo mice, as evidenced by colonization of abundant bacteria, including Oscillospiraceae, Ruminococcaceae, Lachnospiraceae, and Clostridia_UCG-014, and upregulated SCFA production.ConclusionsThis study provided the first evidence that UDCA could confer diarrhea resistance in ESBL-EAEC-infected newborn dairy calves. UDCA blocked bacterial growth and invasion both in vitro and in vivo, alleviated commensal bacterial dysbiosis during ESBL-EAEC infection in neonatal mouse models of sepsis and colitis via the TGR5-NF-κB axis, and upregulated SCFA production in the hindgut digesta. Our findings provide insight into the UDCA-mediated remission of ESBL-EAEC infections and the potential role of UDCA as an antibiotic alternative. Video abstract.

Dataset Information

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

Publications

Red Cabbage Juice-Mediated Gut Microbiota Modulation Improves Intestinal Epithelial Homeostasis and Ameliorates Colitis.

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