Synbiotic supplementation with prebiotic green banana resistant starch and probiotic Bacillus coagulans spores ameliorates gut inflammation in mouse model of inflammatory bowel diseases.

PURPOSE: The research goal is to develop dietary strategies to help address the growing incidence of inflammatory bowel diseases (IBD). This study has investigated the effectiveness of green banana resistant starch (GBRS) and probiotic Bacillus coagulans MTCC5856 spores for the amelioration of dextran-sulfate sodium (DSS)-induced colitis in mice. METHODS: Eight-week-old C57BL/6 mice were fed standard rodent chow diet supplemented with either B. coagulans, GBRS or its synbiotic combination. After 7 days supplementation, colitis was induced by adding 2% DSS in drinking water for 7 days while continuing the supplemented diets. Animal health was monitored and after 14 days all animals were sacrificed to measure the biochemical and histochemical changes associated with each supplement type. RESULTS: The disease activity index and histological damage score for DSS-control mice (6.1, 17.1, respectively) were significantly higher (p < 0.0001) than the healthy mice. Synbiotic supplementation alleviated these markers (- 67%, - 94% respectively) more adequately than B. coagulans (- 52%, - 58% respectively) or GBRS (- 57%, - 26%, respectively) alone. Compared to DSS-control synbiotic supplementation significantly (p < 0.0001) maintained expressions of tight junction proteins. Moreover, synbiotic effects accounted for ~ 40% suppression of IL-1ß and ~ 29% increase in IL-10 levels in serum while also reducing C-reactive protein (- 37%) compared to that of the DSS-control. While, B. coagulans alone could not induce additional levels of short-chain fatty acid (SCFA) production beyond the caecum, the synbiotic combination with GBRS resulted in substantial increased SCFA levels across the whole length of the colon. CONCLUSION: The synbiotic supplementation with B. coagulans and GBRS ameliorated the overall inflammatory status of the experimental IBD model via synergistic functioning. This supports researching its application in mitigating inflammation in human IBD.

Idebenone Protects against Acute Murine Colitis via Antioxidant and Anti-Inflammatory Mechanisms.

Oxidative stress is a key player of the inflammatory cascade responsible for the initiation of ulcerative colitis (UC). Although the short chain quinone idebenone is considered a potent antioxidant and a mitochondrial electron donor, emerging evidence suggests that idebenone also displays anti-inflammatory activity. This study evaluated the impact of idebenone in the widely used dextran sodium sulphate (DSS)-induced mouse model of acute colitis. Acute colitis was induced in C57BL/6J mice via continuous exposure to 2.5% DSS over 7 days. Idebenone was co-administered orally at a dose of 200 mg/kg body weight. Idebenone significantly prevented body weight loss and improved the disease activity index (DAI), colon length, and histopathological score. Consistent with its reported antioxidant function, idebenone significantly reduced the colonic levels of malondialdehyde (MDA) and nitric oxide (NO), and increased the expression of the redox factor NAD(P)H (nicotinamide adenine dinucleotide phosphate) dehydrogenase quinone-1 (NQO-1) in DSS-exposed mice. Immunohistochemistry revealed a significantly increased expression of tight junction proteins, which protect and maintain paracellular intestinal permeability. In support of an anti-inflammatory activity, idebenone significantly attenuated the elevated levels of pro-inflammatory cytokines in colon tissue. These results suggest that idebenone could represent a promising therapeutic strategy to interfere with disease pathology in UC by simultaneously inducing antioxidative and anti-inflammatory pathways.

Short-Chain Naphthoquinone Protects Against Both Acute and Spontaneous Chronic Murine Colitis by Alleviating Inflammatory Responses.

Ulcerative colitis (UC) is characterised by chronic, relapsing, idiopathic, and multifactorial colon inflammation. Recent evidence suggests that mitochondrial dysfunction plays a critical role in the onset and recurrence of this disease. Previous reports highlighted the potential of short-chain quinones (SCQs) for the treatment of mitochondrial dysfunction due to their reversible redox characteristics. We hypothesised that a recently described potent mitoprotective SCQ (UTA77) could ameliorate UC symptoms and pathology. In a dextran sodium sulphate- (DSS-) induced acute colitis model in C57BL/6J mice, UTA77 substantially improved DSS-induced body weight loss, disease activity index (DAI), colon length, and histopathology. UTA77 administration also significantly increased the expression of tight junction (TJ) proteins occludin and zona-occludin 1 (ZO-1), which preserved intestinal barrier integrity. Similar responses were observed in the spontaneous Winnie model of chronic colitis, where UTA77 significantly improved DAI, colon length, and histopathology. Furthermore, UTA77 potently suppressed elevated levels of proinflammatory cytokines and chemokines in colonic explants of both DSS-treated and Winnie mice. These results strongly suggest that UTA77 or its derivatives could be a promising novel therapeutic approach for the treatment of human UC.

Idebenone Protects against Spontaneous Chronic Murine Colitis by Alleviating Endoplasmic Reticulum Stress and Inflammatory Response.

Endoplasmic reticulum (ER) stress in intestinal secretory goblet cells has been linked to the development of ulcerative colitis (UC). Emerging evidence suggests that the short chain quinone drug idebenone displays anti-inflammatory activity in addition to its potent antioxidant and mitochondrial electron donor properties. This study evaluated the impact of idebenone in Winnie mice, that are characterized by spontaneous chronic intestinal inflammation and ER stress caused by a missense mutation in the mucin MUC2 gene. Idebenone (200 mg/kg) was orally administered daily to 5-6 weeks old Winnie mice over a period of 21 days. Idebenone treatment substantially improved body weight gain, disease activity index (DAI), colon length and histopathology score. Immunohistochemistry revealed increased expression of MUC2 protein in goblet cells, consistent with increased MUC2 mRNA levels. Furthermore, idebenone significantly reduced the expression of the ER stress markers C/EBP homologous protein (CHOP), activating transcription factor 6 (ATF6) and X-box binding protein-1 (XBP-1) at both mRNA and protein levels. Idebenone also effectively reduced pro-inflammatory cytokine levels in colonic explants. Taken together, these results indicate that idebenone could represent a potential therapeutic approach against human UC by its strong anti-inflammatory activity and its ability to reduce markers of ER stress.

Modulating the Microbiome and Immune Responses Using Whole Plant Fibre in Synbiotic Combination with Fibre-Digesting Probiotic Attenuates Chronic Colonic Inflammation in Spontaneous Colitic Mice Model of IBD.

A probiotic and prebiotic food ingredient combination was tested for synergistic functioning in modulation of the colonic microbiome and remediation of the gastrointestinal immune and inflammatory responses in a spontaneous colitic mouse model. Bacillus coagulans MTCC5856 spores with capability to metabolise complex plant polysaccharides were supplemented with complex whole-plant prebiotic sugarcane fibre (PSCF). The combined and individual efficacies were tested for their influence on the outcomes of chronic inflammation in Muc2 mutant colitic Winnie mice. The mice were fed normal chow diet supplemented with either ingredient or a combination for 21 days. Synbiotic combined supplementation ameliorated clinical symptoms and histological colonic damage scores more effectively than either B. coagulans or PSCF alone. PSCF and B. coagulans alone also induced considerable immunomodulatory effects. Synbiotic supplementation however was the most efficacious in modulating the overall immune profile compared to the unsupplemented Winnie-control. The augmented synbiotic effect could potentially be due to a combination of increased levels of fermentation products, direct immune-modulating abilities of the components, their capability to reduce colonic epithelial damage and/or modulation of the microbiota. The beneficial effects of the supplementation with a complex plant fibre and a fibre-degrading probiotic parallel the effects seen in human microbiota with high plant fibre diets.

Synbiotic Supplementation Containing Whole Plant Sugar Cane Fibre and Probiotic Spores Potentiates Protective Synergistic Effects in Mouse Model of IBD.

Inflammatory bowel diseases (IBD) are a chronic inflammatory disorders with increasing global incidence. Synbiotic, which is a two-point approach carrying probiotic and prebiotic components in mitigating inflammation in IBD, is thought to be a pragmatic approach owing to the synergistic outcomes. In this study, the impacts of dietary supplementation with probiotic Bacillus coagulans MTCC5856 spores (B. coagulans) and prebiotic whole plant sugar cane fibre (PSCF) was assessed using a murine model of IBD. Eight-week-old C57BL/6 mice were fed a normal chow diet supplemented with either B. coagulans, PSCF or its synbiotic combination. After seven days of supplementation, colitis was induced with dextran sulfate sodium (DSS) in drinking water for seven days during the continuation of the supplemented diets. Synbiotic supplementation ameliorated disease activity index and histological score (-72%, 7.38, respectively), more effectively than either B. coagulans (-47%, 10.1) and PSCF (-53%, 13.0) alone. Synbiotic supplementation also significantly (p < 0.0001) prevented the expression of tight junction proteins and modulated the altered serum IL-1ß (-40%), IL-10 (+26%), and C-reactive protein (CRP) (-39%) levels. Synbiotic supplementations also raised the short-chain fatty acids (SCFA) profile more extensively compared to the unsupplemented DSS-control. The synbiotic health outcome effect of the probiotic and prebiotic combinations may be associated with a synergistic direct immune-regulating efficacy of the components, their ability to protect epithelial integrity, stimulation of probiotic spores by the prebiotic fibre, and/or with stimulation of greater levels of fermentation of fibres releasing SCFAs that mediate the reduction in colonic inflammation. Our model findings suggest synbiotic supplementation should be tested in clinical trials.