Selenium-enriched Bifidobacterium longum DD98 relieves irritable bowel syndrome induced by chronic unpredictable mild stress in mice.

Irritable bowel syndrome (IBS) is a functional intestinal disorder without clear pathological mechanisms. Classical treatments for IBS are not always effective and are usually accompanied by side effects. Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) is a selenized probiotic strain which has shown many beneficial effects on the gastrointestinal tract, but its effects on IBS and the underlying mechanism are unclear. This study aims to investigate the relieving effects of Se-B. longum DD98 on chronic unpredictable mild stress (CUMS)-induced IBS in mice. The model mice were treated with saline, B. longum DD98, or Se-B. longum DD98 while receiving CUMS. The results suggest that Se-B. longum DD98 significantly relieved the intestinal symptoms of IBS mice and reduced intestinal permeability and inflammation. The depression and anxiety-like behaviors of IBS mice were also improved by Se-B. longum DD98. In addition, the expression of serotonin (5-HT), γ-aminobutyric acid (GABA), neuropeptide Y (NPY), and brain-derived neurotrophic factor (BDNF), which are indicators closely related to mood and brain-gut axis, were up-regulated in mice treated with Se-B. longum DD98. Furthermore, the 16S rRNA sequencing study showed that Se-B. longum DD98 effectively restored the relative abundance of intestinal microbes (e.g., Lactobacillus, Desulfovibrio, Akkermansia) and regulated the impaired diversity of gut microbiota in IBS mice. These results suggest that Se-B. longum DD98 positively acts on the brain-gut axis by improving intestinal functions and regulating mood-associated behaviors and indicators of IBS mice. Therefore, this Se-enriched probiotic strain could be considered a promising candidate for the alleviation of CUMS-induced IBS.

Disturbances of the Gut Microbiota and Microbiota-Derived Metabolites in Inflammatory Bowel Disease.

Inflammatory bowel disease (IBD), comprising Crohn's disease (CD) and ulcerative colitis (UC), is characterized as a chronic and recurrent inflammatory disease whose pathogenesis is still elusive. The gut microbiota exerts important and diverse effects on host physiology through maintaining immune balance and generating health-benefiting metabolites. Many studies have demonstrated that IBD is associated with disturbances in the composition and function of the gut microbiota. Both the abundance and diversity of gut microbiota are dramatically decreased in IBD patients. Furthermore, some particular classes of microbiota-derived metabolites, principally short-chain fatty acids, tryptophan, and its metabolites, and bile acids have also been implicated in the pathogenesis of IBD. In this review, we aim to define the disturbance of gut microbiota and the key classes of microbiota-derived metabolites in IBD pathogenesis. In addition, we also focus on scientific evidence on probiotics, not only on the molecular mechanisms underlying the beneficial effects of probiotics on IBD but also the challenges it faces in safe and appropriate application.

Selenium-enriched Bifidobacterium longum DD98 effectively ameliorates dextran sulfate sodium-induced ulcerative colitis in mice.

The pathogenesis of ulcerative colitis (UC) is complicated with impaired intestinal epithelial barrier and imbalanced gut microbiota. Both selenium and probiotics have shown effects in regulating intestinal flora and ameliorating UC. The objective of this study is to investigate the alleviating effects of Selenium-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) on dextran sulfate sodium (DSS)-induced colitis in mice and explore the underlying mechanism. After treatment of B. longum DD98, Se-B. longum DD98, and sulfasalazine for 3 weeks, the disease severity of UC mice was decreased, with colon lengthened and pathological phenotype improved. The expression of pro-inflammatory cytokines and oxidative stress parameters were also decreased. Thus, Se-B. longum DD98 showed a stronger effect on relieving the aforementioned symptoms caused by DSS-induced colitis. Exploration of the potential mechanism demonstrated that Se-B. longum DD98 showed higher activities to suppress the inflammatory response by inhibiting the activation of the toll-like receptor 4 (TLR4), compared to B. longum DD98 and sulfasalazine. Se-B. longum DD98 also significantly improved the intestinal barrier integrity by increasing the expression of tight junction proteins including ZO-1 and occludin. 16S rDNA sequencing analyses showed that Se-B. longum DD98 improved the diversity of the intestinal flora and promoted the abundance of health-benefiting taxa including Lachnospiraceae, Lactobacillaceae, and Prevotellaceae in family level. In conclusion, compared to B. longum DD98 and sulfasalazine, Se-B. longum DD98 showed stronger therapeutic effects on DSS-induced colitis in mice and might be a promising candidate for the treatment of UC.

Selenium-enriched Bifidobacterium longum DD98 attenuates irinotecan-induced intestinal and hepatic toxicity in vitro and in vivo.

Irinotecan (CPT-11) is a camptothecin chemotherapy drug largely used in treating cancers. However, its strong adverse effects, such as gastrointestinal and hepatic toxicities, tend to reduce the patients' life qualities and to limit the clinical use of CPT-11. The protective roles of selenium (Se) and probiotics against CPT-11-induced toxicity have been widely reported. However, the application of Se-enriched probiotics in the adjuvant therapy of CPT-11 has not been well explored. The purpose of this study is to evaluate the in-vitro and in-vivo effects of Se-enriched Bifidobacterium longum DD98 (Se-B. longum DD98) as a chemotherapy preventive agent on alleviating intestinal and hepatic toxicities induced by CPT-11 chemotherapy. The results showed that Se-B. longum DD98 positively regulated the aberrant cell viability and oxidative stress induced by CPT-11 both in human normal liver (L-02) and rat small intestinal epithelial (IEC-6) cell lines. In vivo experiment revealed that Se-B. longum DD98 significantly attenuated intestinal and hepatic toxicities by ameliorating symptoms such as body weight loss and diarrhea, and by improving the biochemical indicators of hepatotoxicity and oxidative stress. Furthermore, we discovered that the protective effects of Se-B. longum DD98 based largely upon decreasing the pro-inflammatory cytokines IL-1ß and IL-18 and enhancing the expression of tight-junction proteins occludin and ZO-1, as well as restoring the composition and diversity of gut microbiota. Results suggested that Se-B. longum DD98 effectively protected livers and intestines against the CPT-11-induced damages, and therefore, could be considered as a promising adjuvant therapeutic agent with CPT-11 for the cancer treatment.

Probiotic Lactobacillus sp. Strains Inhibit Growth, Adhesion, Biofilm Formation, and Gene Expression of Bacterial Vaginosis-Inducing Gardnerella vaginalis.

Gardnerella vaginalis contributes significantly to bacterial vaginosis, which causes an ecological imbalance in vaginal microbiota and presents with the depletion of Lactobacillus sp. Lactobacillus supplementation was reported to be an approach to treat bacterial vaginosis. We investigated the applicability of three Lactobacillus sp. strains (Lactobacillus delbrueckii DM8909, Lactiplantibacillus plantarum ATCC14917, and Lactiplantibacillus plantarum ZX27) based on their probiotic abilities in vitro. The three candidate Lactobacillus sp. strains for bacterial vaginosis therapy showed distinct properties in auto-aggregation ability, hydrophobicity, adhesion to cervical epithelial cells, and survivability in 0.01% hydrogen peroxide. Lpb. plantarum ZX27 showed a higher yield in producing short-chain fatty acids and lactic acid among the three candidate strains, and all three Lactobacillus sp. strains inhibited the growth and adhesion of G. vaginalis. Furthermore, we discovered that the culture supernatant of Lactobacillus sp. exhibited anti-biofilm activity against G. vaginalis. In particular, the Lpb. plantarum ZX27 supernatant treatment decreased the expression of genes related to virulence factors, adhesion, biofilm formation, metabolism, and antimicrobial resistance in biofilm-forming cells and suspended cells. Moreover, Lactobacillus sp. decreased the upregulated expression of interleukin-8 in HeLa cells induced by G. vaginalis or hydrogen peroxide. These results demonstrate the efficacy of Lactobacillus sp. application for treating bacterial vaginosis by limiting the growth, adhesion, biofilm formation, and virulence properties of G. vaginalis.

Transformation of salvianolic acid B to salvianolic acid a in aqueous solution and the in vitro liver protective effect of the main products.

Salvianolic acid A (Sal A) was considered to be the compound with highest activity in Salvia miltiorrhiza (danshen). Due to its low content in raw materials, many studies reported its preparation from salvianolic acid B (Sal B). However, the process of this transformation is still unknown. Our objective was to find the chemical change of the transformation from Sal B to Sal A. The results showed that Sal B was hydrolyzed to lithospermic acid (LA) first, and the latter was transformed into Sal A in thermal aqueous solution. The radical scavenging ability of Sal A, Sal B, and LA was tested through DPPH, and Sal A showed higher radical elimination ability compared to Sal B and LA. In vitro liver damage was induced by CCl4 in human hepatic WRL68 cell line. Sal A, Sal B, and LA showed liver protective ability in a dose-dependent manner, while Sal A possessed a much higher ability compared to Sal B and LA.

Effects of boiling on chlorogenic acid and the liver protective effects of its main products against CCl4-induced toxicity in vitro.

Chlorogenic acid (3-O-caffeoylquinic acid, CA) is the active component in several botanical beverage, vegetables, fruits, and herbal drugs. The effect of water boiling on the bioactivity of CA was studied. CA could be isomerized to 4-O-caffeoylquinic acid (4-O-CA) and 5-O-caffeoylquinic acid (5-O-CA) in decoctive extraction, and each of the isomers occupied about one-third of the total caffeoylquinic acids. A novel method, using water elution of microsphere resin, was used to purify CA and its 2 isomers. The yield of CA, 4-O-CA, and 5-O-CA was 82%, 5.6%, and 50%, with the purity of 98%, 97%, and 99%, respectively. The DPPH radical scavenging assay showed that 4-O-CA, 5-O-CA, and CA exhibited similar activity. However, there was no significant difference between 4-O-CA and 5-O-CA when used against CCl4-induced toxicity in hepG2 cells. Our studies show that isomerization is the main transformation of CA in boiling, and the decoction could not decrease the anti-oxidant activity of CA.

Enhancement of doxorubicin cytotoxicity by tanshinone IIA in HepG2 human hepatoma cells.

Chlorogenic acid (1), salvianolic acid B (2), and tanshinone IIA (3) are commonly used as chemoprotective agents for chemotherapy in cancer patients. The present study deals with the effect of these three compounds on cytotoxicity of doxorubicin in HepG2 cells. The results showed that 1 and 2 reduced the cytotoxicity of doxorubicin through scavenging ROS generated by doxorubicin in HepG2 cells. The findings suggest that 1 and 2 could enhance the expression of SOD and decrease that of NADPH oxidase, which resulted in the elimination of ROS. On the contrary, 3 enhanced the cytotoxicity of doxorubicin in HepG2 cells. Furthermore, drug interactions between doxorubicin and 3 produce synergistic effects in HepG2 cells.

Biotransformation of salvianolic acid B by Fusarium oxysporum f. sp. Cucumerinum and its two degradation routes.

Resting cells of Fusarium oxysporum f. sp. Cucumerinum (F. oxsporum) were used for the biotransformation of salvianolic acid B (Sal B). Three transformed products, isolithospermic acid, prolithospermic acid and danshensu, were identified on the basis of chemical and spectroscopic data. The stability of the two ester bonds of Sal B was studied and two degradation routes were found. In the biotransformation system, Sal B was transformed into isolithospermic acid first which was then converted into prolithospermic acid. In alkaline solutions, Sal B was transformed into lithospermic acid first which was then converted into prolithospermic acid. This is the first reports of the NMR spectra of isolithospermic acid and this result may indicate the metabolic pathways of Sal B in vivo.

Overexpression of aveBIV leading to the improvement of 4'-epidaunorubicin production in Streptomyces coeruleorubidus strain SIPI-A0707.

The 4'-epidaunorubicin is the semisynthesis precursor of epirubicin which is a clinically useful antitumor drug thought to have slightly less cardiotoxicity than doxorubin. The 4'-epidaunorubicin was formed by overexpression of heterologous Streptomyces avermitilis aveBIV in Streptomyces coeruleorubidus SIPI-A0707 dnmV mutant blocked in the biosynthesis of daunosamine, the deoxysugar component of daunorubicin. But there was a low-yield production of 4'-epidaunorubicin. In our study, product yields were enhanced considerably by increasing aveBIV gene copy number or changing means of aveBIV integration. The 4'-epidaunorubicin titer was improved by around threefold in the recombinant strain DYG1006 with the aveBIV increased threefold copy numbers. The transcript levels of aveBIV gene meet the expectation of fermentation levels of 4'-epidaunorubicin. The method described here provides the means to produce 4'-epidaunorubicin efficiently on an industrial scale.

Microsphere resin chromatography combined with microbial biotransformation for the separation and purification of salvianolic acid B in aqueous extract of roots of Salvia multiorrihza Bunge.

Salvianolic acid B was separated and purified from Salvia miltiorrhiza Bunge (danshen) by microbial transformation together with chromatography of microsphere resin. The aqueous extract of danshen was transformed by Fusarium graminearum in a bioreactor containing phosphate buffer (PBS), in which rosmarinic acid was transformed into danshensu and caffeic acid and the yield of salvianolic acid B was higher than 85%. After biotransformation, salvianolic acid B was purified by microsphere resin. A parallel test for making a comparison of microsphere resin chromatography between elution by methanol water solution and water was done. The purity of salvianolic acid B was up to 95% at the yield of 62% when impurities and salvianolic acid B were eluted by 45% and 55% methanol solution respectively. The purity of salvianolic acid B was up to 99% at the yield of 90% when distilled water was used to elute the impurities and salvianolic acid B. The total yield of salvianolic acid B was up to 75% at the purity over 99% while biotransformation combined with microsphere resin chromatography by water elution. Microbial biotransformation together with water elution of microsphere resin supplied an efficient method to eliminate the micromolecular impurities and a possible method to purify water-soluble compounds in traditional Chinese medicine.