Bifico relieves irritable bowel syndrome by regulating gut microbiota dysbiosis and inflammatory cytokines.

PURPOSE: Gut microbiota dysbiosis, a core pathophysiology of irritable bowel syndrome (IBS), is closely related to immunological and metabolic functions. Gut microbiota-based therapeutics have been recently explored in several studies. Bifico is a probiotic cocktail widely used in gastrointestinal disorders which relate to the imbalance of gut microbiota. However, the efficacy and potential mechanisms of Bifico treatment in IBS remains incompletely understood. METHODS: Adopting a wrap restraint stress (WRS) -induced IBS mice model. Protective effect of Bifico in IBS mice was examined through abdominal withdrawal reflex (AWR) scores. 16S rDNA, 1H nuclear magnetic resonance (1H-NMR) and western blot assays were performed to analyze alterations of gut microbiota, microbiome metabolites and inflammatory cytokines, respectively. RESULTS: Bifico could decrease intestinal visceral hypersensitivity. Although gut microbiota diversity did not increase, composition of gut microbiota was changed after treatment of Bifico, which were characterized by an increase of Proteobacteria phylum and Actinobacteria phylum, Muribaculum genus, Bifidobacterium genus and a decrease of Parabacteroides genus, Sutterella genus and Lactobacillus genus. Moreover, Bifico elevated the concentration of short-chain fatty acids (SCFAs) and reduced protein levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). From further Spearman's correlation analysis, Bifidobacterium genus were positively correlated with SCFAs including propionate, butyrate, valerate and negatively correlated with IL-6 and TNF-α. CONCLUSION: Bifico could alleviate symptoms of IBS mice through regulation of the gut microbiota, elevating production of SCFAs and reducing the colonic inflammatory response.

Bifico Ameliorates Neurological Deficits After Ischemic Stroke in Mice: Transcriptome Profiling.

BACKGROUND/AIM: Evidence suggests that gut microbiota can affect various neurological diseases, including stroke. Stroke patients have an increase in harmful gut bacteria and a decrease in beneficial bacteria. This increases intestinal permeability, increases the risk of infection, and even affects many inflammatory factors. While probiotics may affect stroke prognosis by improving the gut environment. This study aimed to investigate the effect of probiotic Bifico on the neural function in mice after focal cerebral ischemia and explore its mechanisms of action. MATERIALS AND METHODS: A focal cerebral ischemia model was established in mice. Four weeks before modeling, animals were divided into three groups: Stroke plus Vehicle group, Stroke plus Pre-Bifico group and Bifico group. The infarct volume and neurobehaviors were evaluated. Whole-gene expression profiling was performed at different days after treatment (D1, D7, D14, D28) by RNA-seq. Differentially expressed genes (DEGs) were the processed for Gene Ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG). Some inflammation and immune related genes were screened and their expression was analyzed. RESULTS: Compared to the Stroke plus Vehicle group and Bifico group, the infarct volume and neurological score were significantly reduced in the Pre-Bifico group. There were 2 DEGs at D1, 193 DEGs at D7, 70 DEGs at D28 between Stroke plus Pre-Bifico group and Stroke plus Vehicle group. For GO analysis, there were 139 significant terms at D7 and 195 at D28. For KEGG, there were 2 significant pathways at D7 and 9 at D28. Among 87 genes related to inflammation and immunity, 6 DEGs were identified. The expression of CCL9 was significantly elevated at most time points after stroke compared to the Stroke plus Vehicle group, while that of CCL6, CXCL10, CD48, CD72 and CLEC7A was highly expressed only in the recovery stage of stroke. CONCLUSION: Oral pre-treatment with Bifico for 28 days can reduce cerebral infarction and promote recovery of neurological function in stroke mice, which may be ascribed to the regulation of immunity and inflammation in the brain.

MiR-34a promotes fibrosis of hepatic stellate cells via the TGF-ß pathway.

BACKGROUND: Previous studies have confirmed that MicroRNA (miRNA) is a key regulator exhibiting different effects in human liver fibrosis. However, the function of miR-34a in liver fibrosis has not been reported. Hence, this study aimed to investigate the regulatory mechanism of miR-34a in liver fibrosis. METHODS: The expression of miR-34a was measured in fibrosis tissues via the quantitative real-time PCR (qRT-PCR) assay. Subsequently, 30 male C57BL/6J mice were divided into control and treatment groups and used to establish animal models of liver fibrosis to explore the expression level of miR-34a. Moreover, Cell Counting Kit 8 (CCK-8) and transwell assays were preformed to identify the regulatory mechanism of miR-34a in cells. The effect of miR-34a on the activity of transforming growth factor-ß (TGF-ß) pathway was observed by western blot. RESULTS: Up-regulation of miR-34a was detected in fibrosis cells. Moreover, the cellular phenotype was suppressed by miR-34a down-regulation in a primary culture of hepatic stellate cells (HSCs). Besides, it was found that increased miR-34a could significantly promote the invasion and migration of HSCs. Moreover, miR-34a activates HSCs through transforming TGF-ß, α-smooth muscle actin (α-SMA), and Monocyte chemoattractant protein-1 (MCP-1), which further affects liver fibrosis. CONCLUSIONS: MiR-34a promotes the fibrosis of HSCs as well as cell proliferation, migration, and invasion.

The prophylactic effects of BIFICO on the antibiotic-induced gut dysbiosis and gut microbiota.

BACKGROUND: The aim of this study is to evaluate the prophylactic effects of probiotic mixture BIFICO on antibiotic-induced gut dysbiosis (AIGD) and the influence on the change of the gut microbiota. METHODS: We conducted a prospective, randomized, controlled study and divided 196 patients who required intravenous beta-lactam antibiotics into three groups: a control group (no probiotics), a regular group (840 mg of BIFICO), and a double-dosage group (1680 mg of BIFICO). The symptoms of antibiotic-related diarrhea, bloating and abdominal pain and the incidence of AIGD were evaluated 7 days and 8-14 days after antibiotic use, with 10 patients in each group. 16S rDNA sequencing was performed to detect changes of the gut microbiota. RESULTS: Within 7 days of the initiation of antibiotic treatment, the incidences of AIGD in the control group, regular group (840 mg of BIFICO), and double-dosage group (1680 mg of BIFICO) were 21.88%, 14.93%, and 6.15% respectively. On days of 8-14th, the incidences of AIGD in the control group, regular group, and double-dosage group were 25%, 14.93%, and 4.62%, respectively. The incidence of AIGD in the double-dosage group within 7 days and 14 days were both significantly lower than that in relevant control group (P < 0.05). On day 14, the incidence of AIGD in the double-dosage group was lower than that in the regular group (P < 0.05). The number of operational taxonomic units (OTUs) in the control group after antibiotic treatment was significantly reduced compared to that prior to treatment, while those of the regular and double-dosage groups were stable. The species abundance, especially Parabacteroides, Phascolarctobacterium and Roseburia, of the double-dosage group was greater than that of the regular group and the control group. CONCLUSIONS: BIFICO may reduce the occurrence of AIGD in a dose-dependent manner and can stabilize the gut microbiota balance.

An analysis on treatment effect of blue light phototherapy combined with Bifico in treating neonatal hemolytic jaundice.

This study aimed to discuss and evaluate the clinical effect of blue light phototherapy combined with bifico in treating neonatal hemolytic jaundice. One hundred and twenty cases with neonatal hemolytic jaundice were randomly divided into treatment group and control group, 60 cases in each group. Neonatal patients in the control group were treated with traditional treatment, including administration of enzyme inducer phenobarbital and blue light phototherapy for 8 consecutive hours every day. Neonatal patients in the treatment group received bifico orally based on traditional treatment. Clinical effects of the two groups were observed after one course of treatment (7 days as one course). During the first course, serum bilirubin level in the treatment group treated with blue light phototherapy combined with bifico declined more rapidly (P<0.01) and more significantly (P<0.01) than that in the control group, and the mean time for eliminating jaundice was significantly reduced (P<0.05). The total effective rate was 91.67% in the treatment group, while that was 85.00% in the control group, which suggested that the treatment effect of the treatment group was better than that of the control group and the difference between the two groups was statistically significant (P<0.05). Compared with traditional treatment, the treatment effect of blue light phototherapy combined with bifico in treating neonatal hemolytic jaundice is significantly improved and the speed of eliminating jaundice is also higher. Thus, it is worthy to be applied in clinical practice.

Probiotic BIFICO cocktail ameliorates Helicobacter pylori induced gastritis.

AIM: To determine the protective effect of triple viable probiotics on gastritis induced by Helicobacter pylori (H. pylori) and elucidate the possible mechanisms of protection. METHODS: Colonization of BIFICO strains in the mouse stomach was determined by counting colony-forming units per gram of stomach tissue. After treatment with or without BIFICO, inflammation and H. pylori colonization in the mouse stomach were analyzed by hematoxylin and eosin and Giemsa staining, respectively. Cytokine levels were determined by enzyme-linked immunosorbent assay and Milliplex. The activation of nuclear factor (NF)-κB and MAPK signaling in human gastric epithelial cells was evaluated by Western blot analysis. Quantitative reverse transcription-polymerase chain reaction was used to quantify TLR2, TLR4 and MyD88 mRNA expression in the mouse stomach. RESULTS: We demonstrated that BIFICO, which contains a mixture of Enterococcus faecalis, Bifidobacterium longum and Lactobacillus acidophilus, was tolerant to the mouse stomach environment and was able to survive both the 8-h and 3-d courses of administration. Although BIFICO treatment had no effect on the colonization of H. pylori in the mouse stomach, it ameliorated H. pylori-induced gastritis by significantly inhibiting the expression of cytokines and chemokines such as TNF-α, IL-1ß, IL-10, IL-6, G-CSF and MIP-2 (P < 0.05). These results led us to hypothesize that BIFICO treatment would diminish the H. pylori-induced inflammatory response in gastric mucosal epithelial cells in vitro via the NF-κB and MAPK signaling pathways. Indeed, we observed a decrease in the expression of the NF-κB subunit p65 and in the phosphorylation of IκB-α, ERK and p38. Moreover, there was a significant decrease in the production of IL-8, TNF-α, G-CSF and GM-CSF (P < 0.05), and the increased expression of TLR2, TLR4 and MyD88 induced by H. pylori in the stomach was also significantly reduced following BIFICO treatment (P < 0.05). CONCLUSION: Our results suggest that the probiotic cocktail BIFICO can ameliorate H. pylori-induced gastritis by inhibiting the inflammatory response in gastric epithelial cells.

The effect of Succinate injection combined with Bifico on the myocardial enzymes changes of the children with rotavirus enteritis / 国际中医中药杂志

Objective To observe the effect of Succinate injection combined with Bifico on the myocardial enzymes changes of the children with rotavirus enteritis.Methods A total of 146 children with rotavirus enteritis were enrolled and included in this study. Children were randomly divided into the control group (n=73) and the observation group (n=73). The control group was received Bifico on the basis of routine treatment, and observation group was received Succinate injection combined with Bifico. The IL-17, IL-6, TNF-?, LDH, CK, and CKMB was detected by ELISA. The rates of clinical effects was compared.Results After treatment, the IL-17 (22.35 ± 4.21 ng/mlvs. 30.24 ± 6.07 ng/ml,t=2.395), IL-6(31.26 ± 6.14 ng/mlvs. 43.72 ± 8.22 ng/ml,t=2.347), TNF-? (35.62 ± 6.24 ng/mlvs. 49.18 ± 8.72 ng/ml,t=2.421), LDH (135.16 ± 31.25 U/Lvs. 174.08 ± 40.22 U/L,t=2.373), CK (37.82 ± 7.39 U/Lvs. 50.21 ± 11.16 U/L,t=2.385), and CKMB (90.14 ± 11.63 U/Lvs. 113.22 ± 18.35 U/L,t=2.392) in the observation group were lower than those in the control group (P<0.05). The rates of clinical effects was 94.5% (69/73) in the observation group and 83.6% (61/73) in the control group. There was significant difference between the two groups (χ2=2.352,P=0.047).Conclusions The Succinate injection combined with Bifico could reduce the inflammatory indices and alleviate the myocardial injury in the RVE patients.

Efficacy of Bifico particles combined with Qiuxieling granule in treatment of infant with rotavirus enteritis / 中国现代医生

Objective To observe the effect of Bifico particles combined with Qiuxieling granule in the treatment of infantile rotavirus enteritis. Methods Children with infantile rotavirus enteritis in our hospital, with 74 patients in the control group and the observation group each. Patients in control group were taken montmorillonite and patients in observation group were taken Bifico particles combined with Qiuxieling granule, the course of treatment was 3 successive days,then the therapeutic effects in the two groups were evaluated after 5 days. Results Clinical symptoms,the fecal bifidobacterium and stool fecal lactose before therapy were compared, there were no significant difference between the two groups (P>0.05). After therapy, the vomiting times and the frequency of diarrhea in the observation group were significantly less than the control group (P<0.01). The fecal bifidobacterium in the observation group was significantly more than the control group (u=8.49,P<0.01). The stool fecal lactose in the observation group was significantly more than the control group (χ2=15.39,P<0.01). Conclusion It has a definite therapeutic effect of Bifico particles combined with Qiuxieling granule in treatment of infant with rotavirus enteritis,and it deserves popularization and application.

Analysis of the clinical effect on C-IBS treated with tegaserod and bifico combined / 中国基层医药

Objective To study the clinical effect on C-IBS treated with tegaserod and bifico combined. Methods 156 patients were randomly divided into one therapy group (group A) and two control group (group B, group C). Patients in the group A were given tegaserod and bifico therapy, while those in group B were given tegaserod therapy and group C were given bifico therapy. Results After 4 weeks' clinical treatment, the rates of remission were 94.6% in group A,7 9.1 % in group B and 54.2% in group C. There were significant statistical differences among three groups(P

Effects of probiotics on the gut flora and mucosal tumor necrosis factor?expression in rats with experimental colitis / 中华消化杂志

Objective To evaluate the effects of probioties on inflammation,intestinal flora and mucosal tumor necrosis factor alpha(TNF-?)expression in experimental colitis rats.Methods Thirty Wistar rats were randomly divided into normal control group(NC),model control group(UC),and pro- biotics treatment group(PC).The experimental colitis were induced by trinitrobenzene sulfonie acid (TNBS)/ethanol enema.Rats in PC group were fed with Bifico[live probiotics of combined bifidobacte- rium(Bif),lactobacillus (Lac) and enterococcus]by 2.2?10~9 colony-forming unit (CFU)/d for 4 weeks.Inflammatory scores and mucosal morphological changes under light microscopy were studied. Plasma endotoxin levels,expressions of TNF-?and interleukin-6 (IL-6) in mueosa were measured. Enteric microorganisms in cecum were fostered with standard methods.Results Inflammatory scores in PC group decreased compared with those in UC group(7.94?0.85 vs 10.25?1.36,P＜0.05),but still higher than those in NC group(7.94?0.85 vs 4.35?0.88,P＜0.01).There was a significant alteration in the enteric microbial flora,Bif and Lac were decreased significantly in UC group,Bifico supplement ameliorated this imbalance.Plasma endotoxin and mucosal TNF-?levels in PC were lower than those in UC group[endotoxin:(93.33?21.22)pg/ml vs (121.25?39.07)pg/ml;TNF-?:67.51?14.63 vs 85.99?18.17,P＜0.05],but higher than those in NC group[endotoxin:(93.33?21.22) pg/ml vs(35.20?15.12)pg/ml;TNF+?:67.51?14.63 vs 43.28 4?19.98,P＜0.01].There was no statistically significant difference in mucosal IL-6 levels between PC group and UC group,though its level in PC group was lower than that in UC group(155.22?34.01 vs 184.09?29.11,P＞0.05),but higher than that in NC group(155.22?34.01 vs 108.73?37.35,P＜0.01).Conclusions Probiotics can attenuate inflammation of experimental colitis of rats through reinstituting gut flora bal- anee.Improving gut flora imbalance,reducing endotoxin and pro-inflammatory cytokines may be the effects of probiotics.