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

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.

Thermodynamic analysis of the pathway for ethanol production from cellobiose in Clostridium thermocellum.

Clostridium thermocellum is a candidate for consolidated bioprocessing by carrying out both cellulose solubilization and fermentation. However, despite significant efforts the maximum ethanol titer achieved to date remains below industrially required targets. Several studies have analyzed the impact of increasing ethanol concentration on C. thermocellum's membrane properties, cofactor pool ratios, and altered enzyme regulation. In this study, we explore the extent to which thermodynamic equilibrium limits maximum ethanol titer. We used the max-min driving force (MDF) algorithm (Noor et al., 2014) to identify the range of allowable metabolite concentrations that maintain a negative free energy change for all reaction steps in the pathway from cellobiose to ethanol. To this end, we used a time-series metabolite concentration dataset to flag five reactions (phosphofructokinase (PFK), fructose bisphosphate aldolase (FBA), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), aldehyde dehydrogenase (ALDH) and alcohol dehydrogenase (ADH)) which become thermodynamic bottlenecks under high external ethanol concentrations. Thermodynamic analysis was also deployed in a prospective mode to evaluate genetic interventions which can improve pathway thermodynamics by generating minimal set of reactions or elementary flux modes (EFMs) which possess unique genetic variations while ensuring mass and redox balance with ethanol production. MDF evaluation of all generated (336) EFMs indicated that, i) pyruvate phosphate dikinase (PPDK) has a higher pathway MDF than the malate shunt alternative due to limiting CO2 concentrations under physiological conditions, and ii) NADPH-dependent glyceraldehyde-3-phosphate dehydrogenase (GAPN) can alleviate thermodynamic bottlenecks at high ethanol concentrations due to cofactor modification and reduction in ATP generation. The combination of ATP linked phosphofructokinase (PFK-ATP) and NADPH linked alcohol dehydrogenase (ADH-NADPH) with NADPH linked aldehyde dehydrogenase (ALDH-NADPH) or ferredoxin: NADP â€‹+ â€‹oxidoreductase (NADPH-FNOR) emerges as the best intervention strategy for ethanol production that balances MDF improvements with ATP generation, and appears to functionally reproduce the pathway employed by the ethanologen Thermoanaerobacterium saccharolyticum. Expanding the list of measured intracellular metabolites and improving the quantification accuracy of measurements was found to improve the fidelity of pathway thermodynamics analysis in C. thermocellum. This study demonstrates even before addressing an organism's enzyme kinetics and allosteric regulations, pathway thermodynamics can flag pathway bottlenecks and identify testable strategies for enhancing pathway thermodynamic feasibility and function.

Red cabbage juice-mediated gut microbiota modulation improves intestinal epithelial homeostasis and ameliorates colitis.

Gut microbiota plays a crucial role in inflammatory bowel disease (IBD) and has therapeutic benefits. Thus, targeting the gut microbiota is a promising therapeutic approach for IBD treatment. We recently found that red cabbage juice (RCJ) ameliorates dextran sulfate sodium (DSS)-induced colitis in mice. However, the underlying mechanisms remain unknown. The current study investigated the modulation of gut microbiota in response to treatment with RCJ to ameliorate the DSS colitis. The initial results demonstrated that mice treated with DSS + RCJ showed increased body weight and decreased diarrhea and blood in feces compared to the DSS alone group. RCJ ameliorated colitis by regulating the intestinal barrier function by reducing the number of apoptotic cells, improving colonic protective mucin, and increasing tight junction protein in RCJ + DSS groups compared to the DSS group. Short-gun metagenomic analysis revealed significant enrichment of short-chain fatty acid (SCFAs)-producing bacteria (Butyrivibrio, Ruminococcaceae, Acetatifactor muris, Rosburia Sp. CAG:303 , Dorea Sp. 5-2) increased PPAR-© activation, leading to repression of the nuclear factor κB (NFκB) signaling pathway, thus decreasing the production of crucial inflammatory cytokines and chemokines in the RCJ + DSS groups compared to the DSS group. Pathway abundance analysis showed an increased abundance of the SCFA pathway, reduced histidine degradation ( Bacteroides sartorii, and Bacteroides caecimuris ), and LCFA production in the RCJ+DSS treated group, suggesting the promotion of good colonic health. Furthermore, increased T-reg (FOXP3+) cells in the colon were due to SCFAs produced by the gut microbiota, which was corroborated by an increase in IL-10, a vital anti-inflammatory cytokine. Thus, our study provides the first evidence that RCJ ameliorates colonic inflammation by modulating the gut microbiota.