Effect of Bifidobacterium animalis subsp. lactis SF on enhancing the tumor suppression of irinotecan by regulating the intestinal flora.

The gut microbiota plays a role in tumor therapy by participating in immune regulation. Here, we demonstrated through 8-day probiotic supplementation experiments and fecal microbiota transplantation experiments that Bifidobacterium animalis subsp. lactis SF enhanced the antitumor effect of irinotecan and prevented the occurrence of intestinal damage by modulating the gut microbiota and reducing the relative abundance of pro-inflammatory microbiota. Therefore, the intestinal inflammation was inhibited, the TGF-ß leakage was reduced, and the PI3K/AKT pathway activation was inhibited. Thus, the tumor apoptotic autophagy was finally promoted. Simultaneously, the reduction of TGF-ß relieved the immunosuppression caused by CPT-11, promoted the differentiation of CD4+ and CD8+ T cells in tumor tissue, and consequently inhibited tumor growth and invasion. This study disclosed the mechanism of B. lactis SF assisting CPT-11 in antitumor activity and suggested that B. lactis SF plays a new role in anticancer effects as a nutritional intervention.

Impact of probiotics on pathogen survival in an innovative human plasma biofilm model (hpBIOM).

BACKGROUND: Despite of medical advances, the number of patients suffering on non-healing chronic wounds is still increasing. This fact is attended by physical and emotional distress and an economic load. The majority of chronic wounds are infected of harmful microbials in a protecting extracellular matrix. These biofilms inhibit wound healing. Biofilm-growing bacteria developed unique survival properties, which still challenge the appropriate wound therapy. The present in-vitro biofilm models are not suitable for translational research. By means of a novel in-vivo like human plasma biofilm model (hpBIOM), this study systematically analysed the influence of 3 probiotics on the survival of five clinically relevant pathogenic microorganisms. METHODS: Human plasma was used to produce the innovate biofilm. Pathogenic microorganisms were administered to the plasma. By stimulating the production of a fibrin scaffold, stable coagula-like discs with integrated pathogens were produced. The five clinically relevant pathogens P. aeruginosa, S. aureus, S. epidermidis, E. faecium and C. albicans were challenged to the probiotics L. plantarum, B. lactis and S. cerevisiae. The probiotics were administered on top of the biofilm and the survival was quantified after 4 h and 24 h of incubation. For statistics, two-way ANOVA with post-hoc Tukey's HSD test was applied. P-value > 0.05 was considered to be significant. RESULTS: SEM micrographs depicted the pathogens on the surface of the fibrin scaffold, arranged in close proximity and produced the glycocalyx. The application of probiotics induced different growth-reducing capacities towards the pathogens. B. lactis and S. cerevisiae showed slight bacteria-reducing properties. The survival of C. albicans was not affected at all. The most antimicrobial activity was detected after the treatment with L. plantarum. CONCLUSIONS: This study successfully reproduced a novel human biofilm model, which provides a human wound milieu and individual immune competence. The success of bacteriotherapy is dependent on the strain combination, the number of probiotics and the activity of the immune cells. The eradicating effect of L. plantarum on P. aeruginosa should be emphasized.

A comparison of two probiotic strains of bifidobacteria in premature infants.

OBJECTIVE: To determine the impact of 2 probiotic bifidobacteria on the fecal microbiota of premature infants fed either human milk or formula. STUDY DESIGN: In the first of two phase 1 clinical trials, 12 premature infants receiving formula feedings were assigned randomly to receive either Bifidobacterium longum ssp infantis or Bifidobacterium animalis ssp lactis in increasing doses during a 5-week period. In the second, 9 premature infants receiving their mother's milk received each of the two bifidobacteria for 2 weeks separated by a 1-week washout period. Serial stool specimens from each infant were analyzed by terminal restriction fragment-length polymorphism and quantitative polymerase chain reaction for bacterial composition. RESULTS: Among the formula-fed infants, there was a greater increase in fecal bifidobacteria among infants receiving B infantis (Binf) than those receiving B lactis (Blac). This difference was most marked at a dose of 1.4 × 10(9) colony-forming units twice daily (P < .05). Bacterial diversity improved over dose/time in those infants receiving Binf. Among the human milk-fed infants, greater increases in fecal bifidobacteria and decreases in γ-Proteobacteria followed the administration of Binf than Blac. The B longum group (which includes Binf but not Blac) was the dominant bifidobacteria among the human milk-fed infants, regardless of the probiotic administered. CONCLUSIONS: Binf was more effective at colonizing the fecal microbiota than Blac in both formula-fed and human milk-fed premature infants. The combination of human milk plus Binf resulted in the greatest fecal levels of bifidobacteria.

In Vitro Probiotic Properties of Bifidobacterium animalis subsp. lactis SF and Its Alleviating Effect on Non-Alcoholic Fatty Liver Disease.

Nonalcoholic fatty liver disease (NAFLD) is a common chronic liver disease with many influencing factors. With the increasing role of the gut-liver axis in various liver diseases, research on the prevention and treatment of NAFLD with probiotics is increasing. In the present study, a Bifidobacterium animalis subsp. strain, B. lactis SF, was isolated from the feces of healthy infants and characterized by sequencing of the 16S rDNA. A systematic probiotic evaluation was carried out, and a diet-induced mouse model was constructed to study the effect and mechanism of B. lactis SF on diet-induced NAFLD. Results show that B. lactis SF has excellent gastrointestinal fluid tolerance and intestinal colonization, and strong antibacterial and antioxidant capabilities. In vivo, B. lactis SF modulated intestinal flora, restored the intestinal barrier, and inhibited LPS entrance into the portal circulation, which subsequently inhibited the TLR4/NF-κB and modulated the PI3K-Akt/AMPK signaling pathway, attenuated the inflammatory response, and reduced lipid accumulation. In addition, B. lactis SF attenuated oxidative stress and further alleviated autophagy, resulting in an ameliorative effect on NAFLD. Therefore, our study provides a new dietary method for the treatment of NAFLD.

A Fermented Milk Product Containing B. lactis CNCM I-2494 Improves the Tolerance of a Plant-Based Diet in Patients with Disorders of Gut-Brain Interactions.

Healthy, plant-based diets, rich in fermentable residues, may induce gas-related symptoms. The aim of this exploratory study was to assess the effects of a fermented milk product, containing probiotics, on the tolerance of a healthy diet in patients with disorders of gut-brain interactions (DGBI), complaining of excessive flatulence. In an open design, a 3-day healthy, mostly plant-based diet was administered to patients with DGBI (52 included, 43 completed) before and at the end of 28 days of consumption of a fermented milk product (FMP) containing Bifidobacterium animalis subsp. lactis CNCM I-2494 and lactic acid bacteria. As compared to a habitual diet, the flatulogenic diet increased the perception of digestive symptoms (flatulence score 7.1 ± 1.6 vs. 5.8 ± 1.9; p < 0.05) and the daily number of anal gas evacuations (22.4 ± 12.5 vs. 16.5 ± 10.2; p < 0.0001). FMP consumption reduced the flatulence sensation score (by -1.6 ± 2.2; p < 0.05) and the daily number of anal gas evacuations (by -5.3 ± 8.2; p < 0.0001). FMP consumption did not significantly alter the overall gut microbiota composition, but some changes in the microbiota correlated with the observed clinical improvement. The consumption of a product containing B. lactis CNCM I-2494 improved the tolerance of a healthy diet in patients with DGBI, and this effect may be mediated, in part, by the metabolic activity of the microbiota.

Sugarcane molasses enhances TGF-ß secretion and FOXP3 gene expression by Bifidobacterium Animalis Subsp. Lactis stimulated PBMCs of Ulcerative Colitis patients.

Ulcerative colitis (UC) is one of the inflammatory diseases of the gut with frequent bloody diarrhea leads to increased rates of anemia. Evidences indicate the immunomodulation disorders in the response to intestinal microbiota in UC. Although sugarcane molasses, rich in necessary minerals and vitamins, could be a good support nutrient but its effect on immune system of UC patients is unknown. To determine how the immune system of UC patients responds to molasses this study was planned. Bifidobacterium lactis were cultivated on MRS broth. PBMCs of 12 UC patients were separated by Ficoll-Hypaque centrifugation and co-cultured with different concentrations of UV killed bacteria and/or molasses in RPMI-1640 plus 10 % FCS. The gene expression of FoxP3 was measured by real-time PCR. TGF-ß and TNF-α were measured in supernatant of PBMCs by ELISA. Sugarcane molasses and B. lactis significantly augmented TGF-ß compared to control (p < 0.01 and p < 0.001 respectively). The secretion levels of TGF-ß by B. lactis plus molasses compared to B. lactis stimulated PBMCs was significantly higher (p < 0.05) but the level of TNF-α by PBMCs after 2/4/12 h incubation with B. lactis plus molasses compared to B. lactis alone was not changed (p > 0.2). The level of FOXP3 expression after treatment with molasses was increased significantly (p < 0.05). These data show that if sugarcane molasses added to B. lactis, not only do not increase the pro-inflammatory cytokine, TNF-α, but also augments the anti-inflammatory cytokine, TGF-ß by PBMCs. Therefore, these results pave the way for further investigation to show sugarcane molasses as a safe support to compensate the lost nutrients in UC patients.

Early Benefits of a Starter Formula Enriched in Prebiotics and Probiotics on the Gut Microbiota of Healthy Infants Born to HIV+ Mothers: A Randomized Double-Blind Controlled Trial.

The gut microbiota of infants is shaped by both the mode of delivery and the type of feeding. The gut of vaginally and cesarean-delivered infants is colonized at different rates and with different bacterial species, leading to differences in the gut microbial composition, which may persist up to 6 months. In a multicenter, randomized, controlled, double-blind trial conducted in South Africa, we tested the effect of a formula supplemented with a prebiotic (a mixture of bovine milk-derived oligosaccharides [BMOS] generated from whey permeate and containing galactooligosaccharides and milk oligosaccharides such as 3'- and 6'-sialyllactose) and the probiotic Bifidobacterium animalis subsp. lactis (B. lactis) strain CNCM I-3446 on the bifidobacteria levels in the gut of infants born vaginally or via cesarean section in early life. Additionally, the safety of the new formulation was evaluated. A total of 430 healthy, full-term infants born to HIV-positive mothers who had elected to feed their child beginning from birth (≤3 days old) exclusively with formula were randomized into this multicenter trial of four parallel groups. A total of 421 infants who had any study formula intake were included in the full analysis set (FAS). The first two groups consisted of cesarean-delivered infants assigned to the Test formula (n = 92) (a starter infant formula [IF] containing BMOS at a total oligosaccharide concentration of 5.8 ± 1.0 g/100 g of powder formula [8 g/L in the reconstituted formula] + B. lactis [1 × 107 colony-forming units {cfu}/g]) or a Control IF (n = 101); the second two groups consisted of vaginally delivered infants randomized to the same Test (n = 115) or Control (n = 113) formulas from the time of enrollment to 6 months. The primary efficacy outcome was fecal bifidobacteria count at 10 days, and the primary safety outcome was daily weight gain (g/d) between 10 days and 4 months. At 10 days, fecal bifidobacteria counts were significantly higher in the Test formula than in the Control formula group among infants with cesarean birth (median [range] log: 9.41 [6.30-10.94] cfu/g versus 6.30 [6.30-10.51] cfu/g; P = 0.002) but not among those with vaginal birth (median [range] log: 10.06 [5.93-10.77] cfu/g versus 9.85 [6.15-10.79] cfu/g; P = 0.126). The lower bound of the two-sided 95% confidence interval of the difference in the mean daily weight gain between the Test and Control formula groups was more than -3 g/d in both the vaginally and cesarean-delivered infants, indicating that growth in the Test formula-fed infants was not inferior to that of Control formula-fed infants. At 10 days and 4 weeks, the fecal pH of infants fed the Test formula was significantly lower than in those fed the Control formula, irrespective of mode of delivery: for vaginal delivery: 4.93 versus 5.59; P < 0.001 (10 days) and 5.01 versus 5.71; P < 0.001 (4 weeks); for cesarean delivery: 5.14 versus 5.65, P = 0.009 (10 days) and 5.06 versus 5.75, P < 0.001 (4 weeks). At 3 months, this acidification effect only persisted among cesarean-born infants. IF supplemented with the prebiotic BMOS and probiotic B. lactis induced a strong bifidogenic effect in both delivering modes, but more explicitly correcting the low bifidobacteria level found in cesarean-born infants from birth. The supplemented IF lowered the fecal pH and improved the fecal microbiota in both normal and cesarean-delivered infants. The use of bifidobacteria as a probiotic even in infants who are immunologically at risk is safe and well tolerated.

Effect of Infant Formula Containing a Low Dose of the Probiotic Bifidobacterium lactis CNCM I-3446 on Immune and Gut Functions in C-Section Delivered Babies: A Pilot Study.

BACKGROUND: In the absence of breast-feeding and its immunomodulatory factors, supplementation of starter infant formula (IF) with probiotics is currently used to support immune functions and gut development. AIM: To assess whether immune-related beneficial effects of regular dose (10(7) CFU/g of powder) of the probiotic Bifidobacterium lactis CNCM I-3446 (hereafter named B. lactis) in starter IF supplementation can be maintained with starter IF containing a low dose (10(4) CFU/g of powder) of B. lactis. METHOD: This trial was designed as a pilot, prospective, double-blind, randomized, single-center clinical trial of two parallel groups (n = 77 infants/group) of C-section delivered infants receiving a starter IF containing either low dose or regular dose of the probiotic B. lactis from birth to six months of age. In addition, a reference group of infants breast-fed for a minimum of four months (n = 44 infants), also born by C-section, were included. All groups were then provided follow-up formula without B. lactis up to 12 months of age. Occurrence of diarrhea, immune and gut maturation, responses to vaccinations, and growth were assessed from birth to 12 months. The effect of low-dose B. lactis formula was compared to regular-dose B. lactis formula, considered as reference for IF with probiotics, and both were further compared to breast-feeding as a physiological reference. RESULTS: Data showed that feeding low-dose B. lactis IF provides similar effects as feeding regular-dose B. lactis IF or breast milk. No consistent statistical differences regarding early life protection against gastrointestinal infections, immune and gut maturation, microbiota establishment, and growth were observed between randomized formula-fed groups as well as with the breast-fed reference group. CONCLUSION: This pilot study suggests that supplementing C-section born neonates with low-dose B. lactis-containing starter formula may impact immune as well as gut maturation similarly to regular-dose B. lactis, close to the breast-feeding reference.