內(nèi)容: This study investigated the preventive effects of soybean meal peptides (SPs) and their purification peptides (GTYW) on acute alcoholic liver injury. We combined the gut microbiota, metabolites, liver inflammation, and oxidative stress indicators to explore the prevention mechanism of SPs and GTYW. Results showed that SPs, GTYW effectively improved the hepatic oxidative stress and inflammatory. Additionally, SPs and GTYW reversed the effects of alcohol on the gut microbiota, which were evident in the increased abundance of Alloprevotella, Parasutterella in the GTYW group and norank_f__Muribaculaceae in the SPs group. Non-targeted metabolomic analysis showed that SPs ameliorated metabolic disorders by regulating phenylalanine, tyrosine and tryptophan biosynthesis, while GTYW regulated metabolites through α-linolenic acid metabolism and phenylalanine metabolism. Furthermore, significant correlations were observed between gut microbiota, metabolites and liver indicators. These findings confirmed that SPs and GTYW can prevent acute alcoholic liver injury.

內(nèi)容: While exerting their metabolic activities in the gastrointestinal milieu, probiotics impact the host well-being by boosting immunity, treating metabolic disorders, and modulating microbiota and metabolome. Due to the high incidence of gluten-based disorders, the present work aims to deeply explore the metabolism of two selected microbial consortia (MCs) during gluten digestion under simulated gastrointestinal conditions. Featured by high protease and peptidase activity, both MCs accounted for different lactic acid bacteria and Bacillus strains that were combined with two commercial protease enzymes. Gluten substrates were used as purified extracts, white and whole wheat breads. Control samples, instead, relied onto the microbial enzyme lack. Twenty-four hours of simulated digestion were sufficient to completely hydrolyze gluten in one of the two MC-containing experimental sets, and the relative 48 h-digested extract did not alter the cytokine expression in duodenal biopsies from celiac disease (CeD) patients. When digested samples were assayed for antioxidant and phytase activities, microbial enzymes demonstrated to significantly improve both 2,2’-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) scavenging activity and to decrease the phytic acid concentration. The inspection of the free amino acid profiles allowed for distinguishing the two MCs, whereas the detection of a heterogeneous panel of volatile organic compounds supported the presence/activity of microbial enzymes without statistically significant differences between MCs. As functional contribution, digested extracts with MCs also proved to reduce the inflammatory cytokine concentrations in cell lines exposed to lipopolysaccharide trigger. Therefore, in line with studies exploring novel adjuvant therapies, the present innovative probiotic consortium featured by high gluten-hydrolyzing metabolism also showed the capability to improve various parameters usually found to be altered in patients affected by gluten-based disorders or CeD.

內(nèi)容: Most Aloe species are used as new food or functional food ingredient. Even though widely known for its health benefits, the anti-inflammatory effects and underlying mechanisms of Aloin (Alo), an anthraquinone compound isolated from plant species of the genus Aloe, remain unidentified. Here, we investigated the protective effects of Alo against cecal ligation and puncture (CLP)-induced sepsis and microflora in mice. Alo significantly improved CLP-induced sepsis and the survival rate of septic mice, downregulated the expression of proinflammatory factors, and decreased the infiltration of inflammatory cells in tissues. Alo upregulated the proportion of peritoneal macrophages, reduced the number of peritoneal bacteria, decreased the content of short-chain fatty acids and bile acids in the abdominal cavity, and suppressed Toll-like receptor (TLR)-2/4/nuclear factor kappa-B (NF-κB)/NOD-like receptor thermal protein domain associated protein 3 (NLRP3)/Caspase-1/3/8 signaling. Furthermore, Alo altered the composition of the microbiome and promoted the growth of Lactobacillus, which showed a stronger anti-inflammatory effect. Whole-genome analysis identified the genes Saa3, Il10, Fpr1, and Eif4a1 associated with the protective effects of Alo in mice with CLP-induced sepsis. Overall, our results provide novel insights into the therapeutic potential and mechanism of action of Alo in the treatment of sepsis.

內(nèi)容: This study aims to uncover the hormetic process of luteolin, a common dietary flavone, in neuronal cells through its role in inducing mitochondrial stress. In rat pheochromocytoma PC12 cells, luteolin at low concentrations caused a mild and reversible loss of mitochondrial membrane potential (MMP), while high concentrations of luteolin triggered intense and sustained depolarization of MMP. The MMP disturbance was shown to have a close association with the trophic and/or toxic effects triggered by luteolin; because the common mitochondrial uncouplers shared similar bi-phase dose-response on cell viability, as that of luteolin. Along with the induced MMP pertubation, luteolin triggered the development of autophagy and mitophagy, as determined by mCherry-GFP-LC3B tandem protein, and by the co-localization of mitochondrial/lysosomal staining. Subsequent application of autophagy inhibitors in the cultures blocked the luteolin-induced neurotrophic activities and sensitized the cells to be less resistant to luteolin-mediated cytotoxicity. Other flavonoids also displayed similar properties in the cultures, indicating that these compounds act as hormetic pharmacological inducers that stimulate cells to become more resilient and adapt to threats. This study provides a unifying mechanistic explanation for the neuro-beneficial effects of luteolin and other flavonoids.

內(nèi)容: Many studies have shown that the development of allergic asthma is associated with intestinal microbiota dysbiosis. Based on the gut-lung axis theory, probiotic intervention may be a potential strategy for respiratory diseases. Lacticaseibacillus paracasei K56 was reported to regulate gut microbiota in mice. However, its effect on allergic asthma has not been reported. In this study, we investigated the effect of the K56 on ovalbumin-induced asthma and its possible mechanisms. Our results showed that K56 reduced asthma symptoms and inflammatory cell infiltration in the lung of asthmatic mice. And K56 regulated the differentiation of helper T cells in the lung and intestine. Results from 16S rRNA gene sequencing showed that K56 prophylaxis significantly elevated the richness of Akkermansia and Burkholderia. Meanwhile, K56 abrogated the decrease in the levels of short-chain fatty acids (SCFAs) in the feces. In addition, a rebound in the mRNA expression of the SCFA receptors was observed after K56 prophylaxis. Notably, the regulatory T cell (Treg) frequencies and the FFAR3 levels were positively correlated. These results suggest that K56 could attenuate asthma, possibly by modulating the intestinal microbiota and regulating Treg differentiation through SCFA metabolized. Our study showed that K56 may be used as a probiotic to prevent pulmonary inflammation and dysbiosis of the intestinal microbiota in allergic asthma.

內(nèi)容: Mastitis often occurs during women’s lactation period, causing great psychological and physical pain to women. Fucoidan, a sulfated polysaccharide obtained from brown algae, has much broader biological properties. However, the roles of fucoidan in lipopolysaccharides (LPS)-induced mastitis are still undiscovered. The present study was aimed to evaluate the influences of fucoidan on LPS-induced mouse mastitis and investigate its possible mechanisms. The expression profiles of fucoidan acting on mastitis were analyzed by network pharmacology. Additionally, mechanism experiments verified the mechanism of fucoidan on mastitis. The results of in vivo study displayed that the treatment of fucoidan to LPS-stimulated mouse mastitis decreased the inflammatory damage, proinflammatory cytokines level and repaired the completeness of blood-milk barrier. In the study of mouse mammary epithelial cells, fucoidan suppressed the secretion of reactive oxygen species (ROS) and enhanced the activity of antioxidant enzymes. Molecular experiments suggested that fucoidan promoted nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear import and autophagy via activating the adenosine 5’-monophosphate-activated protein kinase (AMPK) signaling pathway. The above results indicated that in mastitis, fucoidan promoted Nrf2 nuclear import and autophagy via activating the AMPK signaling pathway, thereby suppressing oxidative stress and inflammatory injury to the mammary glands and protecting the blood-milk barrier.

內(nèi)容: Gut microbiota regulate the activation of adipose browning, which promote energy dissipation and combat diet-induced obesity. Pomegranate peel polyphenols (PPPs) have been shown to reduce obesity, regulate lipid metabolism in adipose tissue, and modulate the composition of gut microbiota in animal fed high-fat diet (HFD). However, the role of gut microbiota in the improvement of obesity by PPPs has not been elucidated. In current study, we applied antibiotics to inhibit gut microbiota in mice fed HFD and treated with PPPs. The results showed that the inhibition of gut microbiota impair the effect of PPPs on reducing obesity and promoting adipose browning, and change the fecal metabolomic profiles in respond to PPPs. Moreover, the inhibition of gut microbiota supressed the promotive effects of PPPs on the levels of Akkermansia and microbiota-related metabolites, such as urolithin A, short-chain fatty acids (SCFAs), and bile acids (BAs), which were associated with activating adipose browning. Therefore, our results suggested that the presence of gut microbiota is essential for PPPs to ameliorate HFD-induced obesity. The related bacteria or metabolites generated by the interaction between PPPs and microbiota promote adipose browning and facilitate the beneficial effects of PPPs.

內(nèi)容: Aflatoxin B1 (AFB1) is a common contaminant in cereals of global concern, and long-term low-dose exposure can adversely affect human health. Here, we showed that populations with dietary patterns characterized by high-fat diet (HFD) might have an increased risk of exposure to high levels of AFB1. Our data indicated that chronic exposure of AFB1 induced “gut-liver axis” injury in mice under HFD and normal diet (ND) patterns. AFB1 further aggravated hepatic and intestinal injury, and intestinal microbiota disruption in HFD mice. Bifidobacterium breve BAA-2849 intervention analysis showed that liver injury and lipid disorders caused by AFB1 exposure were alleviated by regulating the proportions of different gut microbes. We demonstrated through a mice model that the populations with a dietary pattern of HFD might be more susceptible to AFB1 exposure and adverse effects on the gut-liver axis, and the toxicity of AFB1 exposure can be alleviated by regulating the gut microbiota.

內(nèi)容: Long-term intake of high-fat diet (HFD) leads to systemic hypo-inflammation, which is involved in the pathogenesis of many liver diseases. The aim of this study was to evaluate the interventional effect of inulin addition on HFD-induced non-alcoholic fatty liver disease (NAFLD). Here, we assessed liver inflammation and lipid metabolism by enzyme linked immunosorbent assay (ELISA) kits and real-time quantitative polymerase chain reaction (qPCR), and explored its relationship with intestinal flora and metabolites by 16S rDNA gene sequencing and untargeted metabolomics. In addition, we determined the effect of the inositol-requiring enzyme-1α-X-box binding protein 1 (IRE1α-XBP1) pathway on liver macrophage polarization by flow cytometry. In conclusion, our study has demonstrated that inulin ameliorates high levels of bile acids and colonic immune disorders induced by HFD, and improves hepatic macrophage polarization and hepatic lipid metabolism via the intestine-hepatic axis, thus providing a mechanistic basis for therapeutic approaches to modulate bile acids to improve colonic inflammation and NAFLD.

內(nèi)容: Lycii Radicis Cortex (LRC) is a medicinal and food homologous plant with various pharmacological activities, including anti-tumor effects. This study explores the anti-tumor effect of LRC on non-small cell lung cancer (NSCLC) and its molecular mechanism using mice bearing Lewis lung carcinoma cells. LRC significantly suppressed the growth of NSCLC. Besides, RNA sequencing of mice tumors and hematoxylin & eosin and immunofluorescence staining revealed that LRC promoted the infiltration of T lymphocytes, specifically GZMB+CD8+T lymphocytes, in tumor tissues. The Gene Set Enrichment Analysis of spleen RNA indicated that LRC up-regulated PD-1-downstream pathways, suggesting that LRC exerted its effects through the PD-L1/PD-1 pathway. Further experiments revealed that LRC interacted with PD-L1, blocking PD-L1/PD-1 binding and thus restoring the T cell killing activity on tumor cells. Together, these results support using LRC as healthy food to improve anti-tumor immunity in patients with NSCLC.