Casei DG Research Articles

The effectiveness of the use of synbiotics in the complex therapy of acute intestinal infections in children

Relevance. Acute intestinal infections in children retain a high value in the structure of child morbidity and mortality, which necessitates the search for means and methods for their active treatment and improvement of prognosis.
 Aim: to determine the effectiveness of the use of synbiotics in the complex therapy of acute intestinal infections in children at the outpatient stage.
 Materials and methods. Fifty 6–17 years children with mild or moderate acute intestinal infections were examined. The patients were divided into the main group (30 children) and the control group (20 children), the groups were comparable. Patients from the main group, along with pathogenetic therapy, received a combination of Lacticaseibacillus paracasei DG I-1572 DSM 34154 
 (L. casei DG) and fructooligosaccharides (FOS), and children from the control group received only pathogenetic and symptomatic treatment. Clinical symptoms were evaluated over following up included temperature, frequency and, nature of stool, presence and severity of dyspeptic manifestations, nausea, frequency of vomiting, presence and severity of abdominal pain syndrome. Statistical data processing was carried out using statistical analysis Statistica v. 13.0 (StatSoft Inc., USA).
 Results. The combined use of L. casei DG and FOS in the pathogenetic therapy of acute intestinal infections reduces the time of relief of clinical manifestations. The severity of abdominal pain syndrome regresses significantly faster when using this synbiotic. Norma­lization of the frequency and nature of stool occurs significantly faster with the simultaneous appointment of pathogenetic therapy and the synbiotic. The combination of L. casei DG and FOS has demonstrated a high safety profile, side effects have not been reported.
 Conclusion. It is advisable to prescribe the combination of L. casei DG and FOS from the first day of acute intestinal infections alongside with pathogenetic and symptomatic therapy to achieve a clinical effect more quickly.

Probiotic lactobacilli attenuate oxysterols-induced alteration of intestinal epithelial cell monolayer permeability: Focus on tight junction modulation.

Oxidative stress and inflammation lead by dietary oxidised lipids, as oxysterols, have been linked to the loss of intestinal barrier integrity, a crucial event in the initiation and progression of intestinal disorders. In the last decade, probiotic lactobacilli have emerged as an interesting tool to improve intestinal health, thanks to their antioxidant and anti-inflammatory properties. The aim of the present study was to evaluate the ability of two commercial probiotic strains of lactobacilli (Lactiplantibacillus plantarum 299v® (DMS 9843) and Lacticaseibacillus casei DG® (CNCMI-1572)), both as live bacteria and intracellular content, to attenuate the oxysterols-induced alteration of intestinal epithelial Caco-2cell monolayer permeability. Our investigation was focused on the modulation of tight junctions (TJs) proteins, occludin, ZO-1 and JAM-A, in relation to redox-sensitive MAPK p38 activation. Obtained results provided evidence on the ability of the two probiotics to counteract the alteration of monolayer permeability and loss of TJs proteins, at least in part, through the modulation of p38 pathway. The protective action was exerted by live bacteria, whose adhesion to Caco-2cells was not altered by oxysterols, and bacterial intracellular components equally able to interact with the signaling pathway.

P0156 - The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: Results from a phase IV study

P0156 - The use of Lactobacillus casei DG® prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: Results from a phase IV study

The use of Lactobacillus casei DG\xae prevents symptomatic episodes and reduces the antibiotic use in patients affected by chronic bacterial prostatitis: results from a phase IV study

PurposeTo evaluate the efficacy of Lactobacillus paracasei CNCM I-1572 (L. casei DG®) in both prevention of symptomatic recurrences and improvement of quality of life in patients with chronic bacterial prostatitis (CBP).MethodsPatients with CBP attending a single Urological Institution were enrolled in this phase IV study. At enrollment, all patients were treated with antibiotics in agreement with EAU guidelines and then were treated with L. casei DG® (2 capsules/day for 3 months). Clinical and microbiological analyses were carried out before (enrollment, T0) and 6 months (T2) after the treatment. Both safety and adherence to the treatment were evaluated 3 months (T1) after the enrollment. NIH Chronic Prostatitis Symptom Index (CPSI), International Prostate Symptom Score (IPSS) and Quality of Well-Being (QoL) questionnaires were used. The outcome measures were the rate of symptomatic recurrence, changes in questionnaire symptom scores and the reduction of antibiotic use.ResultsEighty-four patients were included. At T2, 61 patients (72.6%) reported a clinical improvement of symptoms with a return to their clinical status before symptoms. A time dependent improvement in clinical symptoms with significant changes in NIH-CPSI, IPSS and QoL (mean difference T2 vs T0: 16.5 ± 3.58; − 11.0 ± 4.32; + 0.3 ± 0.09; p < 0.001), was reported. We recorded that L. casei DG® treatment induced a statistically significant decrease in both (p < 0.001) symptomatic recurrence [1.9/3 months vs 0.5/3 months] and antibiotic use [− 7938 UDD]. No clinically relevant adverse effects were reported.ConclusionsL. casei DG® prevents symptomatic recurrences and improves the quality of life in patients with CBP, reducing the antibiotic use.

ELLSA based profiling of surface glycosylation in microorganisms reveals that ß-glucan rich yeasts' surfaces are selectively recognized with recombinant banana lectin.

The surface of microorganisms is covered with polysaccharide structures which are in immediate contact with receptor structures on host's cells and antibodies. The interaction between microorganisms and their host is dependent on surface glycosylation and in this study we have tested the interaction of plant lectins with different microorganisms. Enzyme-linked lectin sorbent assay - ELLSA was used to test the binding of recombinant Musa acuminata lectin - BL to 27 selected microorganisms and 7 other lectins were used for comparison: Soy bean agglutinin - SBA, Lens culinaris lectin - LCA, Wheat germ agglutinin - WGA, RCA120 - Ricinus communis agglutinin, Con A - from Canavalia ensiformis, Sambucus nigra agglutinin - SNA I and Maackia amurensis agglutinin - MAA. The goal was to define the microorganisms' surface glycosylation by means of interaction with the selected plant lectins and to make a comparison with BL. Among the tested lectins most selective binding was observed for RCA120 which preferentially bound Lactobacillus casei DG. Recombinant banana lectin showed specific binding to all of the tested fungal species. The binding of BL to Candida albicans was further tested with fluorescence microscopy and flow cytometry and it was concluded that this lectin can differentiate ß-glucan rich surfaces. The binding of BL to S. boulardii could be inhibited with ß-glucan from yeast with IC50 1.81μgmL-1 and to P. roqueforti with 1.10μgmL-1. This unique specificity of BL could be exploited for screening purposes and potentially for the detection of ß-glucan in solutions.

935 – Microbiota and Immune Microenvironment in Pouchitis (MEP1): Interim Analysis of a Randomized Controlled Trial on Oral Administration of Lactobacillus Casei Dg For8 Weeks After Ileostomy Closure

935 – Microbiota and Immune Microenvironment in Pouchitis (MEP1): Interim Analysis of a Randomized Controlled Trial on Oral Administration of Lactobacillus Casei Dg For8 Weeks After Ileostomy Closure

Fecal microbiota transplantation for TKI-induced diarrhea in patients with metastatic renal cell carcinoma.

615 Background: Diarrhea is a common adverse event of tyrosine kinase inhibitors (TKI). No standard treatment for TKI-induced diarrhea has been established, although probiotics are commonly used. In several patients TKI dose reduction is necessary. Data showing the interplay between microbiota and TKI-induced diarrhea are reported. The therapeutic modulation of gut microbiota could be useful to ameliorate TKI-related diarrhea. Our study aims to explore the efficacy and safety of fecal microbiota transplantation (FMT), compared with current clinical practice approach, for the treatment of TKI-associated diarrhea in patients with metastatic renal cell carcinoma. Methods: Patients on treatment with Pazopanib/Sunitinib as first line therapy for metastatic renal cell carcinoma and TKI-associated diarrhea (³ 4 stools per day over baseline) were randomize to receive FMT from healthy donor by colonoscopy (fresh faeces) or probiotics (L. casei DG). The primary endpoint was the resolution of TKI-related diarrhea. Baseline fecal samples were collected from all patients and donors. All patients were followed up 7, 15, 30 and 60 days after the treatment for diarrhea. Results: 21 subjects, 10 in FMT arm and 11 in control arm, have been enrolled. At 7 day-follow-up, TKI-related diarrhea disappeared in 10 patients of the FMT group and in 6 patients of the control group (100% vs 54.5%, p = 0.02). At 15-day and 30-day, 9 patients in the FMT group and 0 patients in the control group experienced resolution of diarrhea (90% vs 0%, p = 0.0001). At 60-days 8/10 patients in FMT arm did not have diarrhea. Dose reduction was necessary in 4 patients of the control group. No serious adverse events associated with any of the two treatment protocols were observed. Metagenomic analyses on collected stool samples are ongoing. Conclusions: This open-label randomised controlled trial showed the effectiveness and safety of FMT compared with probiotics in curing TKI-related diarrhea in patients with metastatic renal cell carcinoma, avoiding the necessity of dose reduction. Considering the increasing evidence, the modulation of microbiota trough FMT could also affect the efficacy of immunotherapy for metastatic renal cell carcinoma.

Анализ штамм-специфичных эффектов лактобацилл L. casei DG (L. paracasei CNCM I-1572) и возможность их применения в клинической практике

The effectiveness of probiotics is strain-specific. This paper presents the results of a systematic analysis of the promising lactobacterial strain Lactobacillus paracasei CNCM I-1572 (L. casei DG; L. paracasei DG). L. casei DG well survives in the conditions of the stomach and intestines, supports the beneficial microbiota and inhibits the growth of pathogenic bacteria, exhibits a therapeutic effect in ulcerative colitis, eradication of H. pylori, diverticular bowel disease, and irritable bowel syndrome.

Survival of L. casei DG\xae (Lactobacillus paracasei CNCMI1572) in the gastrointestinal tract of a healthy paediatric population

PurposeAbility to survive the digestive process is a major factor in determining the effectiveness of a probiotic. In this study, the ability of the probiotic L. casei DG® (Lactobacillus paracasei CNCMI1572) to survive gastrointestinal transit in healthy children was investigated for the first time.MethodsTwenty children aged 3–12 years received L. casei DG® as drinkable solution of 1 × 109 colony forming units (CFU), once daily for 7 consecutive days. Recovery in faecal samples was evaluated at baseline and at different time-points during and after administration. Defecation frequency, faeces consistency, digestive function and product safety were also assessed.ResultsNineteen (95%) of the 20 enrolled children presented viable L. casei DG® cells in their faeces at least once during the study, with a maximum count (mean 4.3 log10 CFU/g ± 2.3) reached between day 4 and 6 from the beginning of consumption. Notably, for 11 (57.9%) of the 19 children with viable cells, L. casei DG® survived in faecal samples up to 3 days after treatment end. Defecation frequency, faeces consistency and digestive function did not change considerably during or after study treatment. Safety of the study product was very good.ConclusionsThis study showed for the first time that L. casei DG® survives the gastrointestinal transit when ingested by children with a paediatric probiotic drinkable solution containing 1 × 109 CFU, and persists in the gut up to 3 days after the end of product intake, demonstrating resistance to gastric juices, hydrolytic enzymes and bile acids.

Quantitative Recovery of Viable Lactobacillus paracasei CNCM I-1572 (L. casei DG®) After Gastrointestinal Passage in Healthy Adults.

Probiotics are live microorganisms, and viability after transit through the gastrointestinal tract (GIT) is considered an inherent property of the health benefits of probiotics. The aim of the present study was to quantify the viable and total loads of Lactobacillus paracasei DG cells after passage through the GIT following the consumption of the probiotic product Enterolactis (L. casei DG®; L. paracasei CNCM I-1572; L. paracasei DG) from drinkable vials by healthy adults. We developed a novel method for discriminating and enumerating culturable L. paracasei DG cells based on the unique sticky, filamentous phenotype of this strain on MRS agar containing vancomycin and kanamycin. The identity of DG was also confirmed with strain-specific primers by colony PCR. This method was used for a recovery study of the DG strain to quantify viable cells in the fecal samples of 20 volunteers during a 1-week probiotic consumption period and a 1-week follow-up. We isolated L. paracasei DG from at least one fecal sample from all the volunteers. The highest concentration of viable DG cells [ranging from 3.6 to 6.7 log10 colony-forming unit (CFU) per gram of feces] in the feces was observed between 4 and 8 days from the beginning of Enterolactis intake and for up to 5 days after cessation of intake. As expected, the total DG count determined by real-time quantitative PCR (qPCR) was mostly higher than the viable DG cells recovered. Viable count experiments, carried out by combining ad hoc culture-based discriminative conditions and strain-specific molecular biological protocols, unambiguously demonstrated that L. paracasei DG can survive gastrointestinal transit in healthy adults when ingested as Enterolactis in drinkable vials containing no less than one billion CFU at the end of shelf life.

Antibiotic-induced microbiota perturbation causes gut endocannabinoidome changes, hippocampal neuroglial reorganization and depression in mice

The microbiota-gut-brain axis (MGBA) regulates the reciprocal interaction between chronic inflammatory bowel and psychiatric disorders. This interaction involves multiple pathways that are highly debated. We examined the behavioural, biochemical and electrophysiological alterations, as well as gut microbiota composition in a model of antibiotic-induced experimental dysbiosis. Inflammation of the small intestine was also assessed. Mice were exposed to a mixture of antimicrobials for 2weeks. Afterwards, they received Lactobacillus casei DG (LCDG) or a vehicle for up to 7days via oral gavage.Perturbation of microbiota was accompanied by a general inflammatory state and alteration of some endocannabinoidome members in the gut. Behavioural changes, including increased immobility in the tail suspension test and reduced social recognition were observed, and were associated with altered BDNF/TrkB signalling, TRPV1 phosphorylation and neuronal firing in the hippocampus. Moreover, morphological rearrangements of non-neuronal cells in brain areas controlling emotional behaviour were detected. Subsequent probiotic administration, compared with vehicle, counteracted most of these gut inflammatory, behavioural, biochemical and functional alterations. Interestingly, levels of Lachnospiraceae were found to significantly correlate with the behavioural changes observed in dysbiotic mice. Our findings clarify some of the biomolecular and functional modifications leading to the development of affective disorders associated with gut microbiota alterations.

Bacterial stimuli activate nitric oxide colonic mucosal production in diverticular disease. Protective effects of L. casei DG® (Lactobacillus paracasei CNCM I-1572).

Micro-inflammation and changes in gut microbiota may play a role in the pathogenesis of diverticular disease (DD). The objective of this article is to evaluate the expression of nitric oxide (NO)-related mediators and S100B in colonic mucosa of patients with DD in an ex vivo model of bacterial infection. Intestinal biopsies obtained from patients with diverticulosis, symptomatic uncomplicated diverticular disease (SUDD) and SUDD with previous acute diverticulitis (SUDD+AD) were stimulated with the probiotic L. casei DG® (LCDG) and/or the pathogen enteroinvasive Escherichia coli (EIEC). S100B, NO release and iNOS expression were then evaluated. Basal iNOS expression was significantly increased in SUDD and SUDD+AD patients. Basal NO expression was significantly increased in SUDD+AD. No differences in S100B release were found. In all groups, iNOS expression was significantly increased by EIEC and reduced by LCDG. In all groups, except for SUDD+AD, EIEC significantly increased NO release, whereas no increase was observed when LCDG was added to biopsies. EIEC did not induce significant changes in S100B release. Colonic mucosa of patients with DD is characterized by a different reactivity toward pathogenic stimuli. LCDG plays a role in counteracting the pro-inflammatory effects exerted by EIEC, suggesting a beneficial role of this probiotic in DD.

Lactobacillus casei DG and its postbiotic reduce the inflammatory mucosal response: an ex-vivo organ culture model of post-infectious irritable bowel syndrome

BackgroundThe evidence on the role of gut microbiota in post-infectious irritable bowel syndrome (PI-IBS) is convincing. Lactobacillus spp. positively affect IBS symptoms, although the mechanisms through which probiotics exert their beneficial effects are largely unknown. The aim of the study is to evaluate the role of Lactobacillus casei DG (LC-DG) and its postbiotic (PB) in modulating the inflammatory/immune-response in PI-IBS in an ex-vivo organ culture model.MethodsEx vivo cultures of ileal and colonic mucosa from 10 PI-IBS, diarrhea predominant subtype (D) patients, and 10 healthy controls (HC) were treated with LPS, LC-DG and PB. Interleukin (IL)-1α, IL-6, IL-8 and IL-10 mRNA levels were assessed by real-time PCR and Toll like receptor 4 (TLR-4) protein expression by Western blotting.ResultsAt baseline, IL-1α, IL-6 and IL-8 mRNA levels as well as TLR-4 protein expression were significantly higher while IL-10 mRNA levels were lower in PI-IBS D than in HC in both ileum and colon. LC-DG and PB significantly reduced the mRNA levels of pro-inflammatory cytokines and TLR-4 while increased that of IL-10 after LPS stimulation. The protective effect was more pronounced for PB than LC-DG treatment.ConclusionLC-DG and its PB attenuate the inflammatory mucosal response in an ex-vivo organ culture model of PI-IBS D.

P.03.15: Lactobacillus Casei DG and its Postbiotic Reduce the Inflammatory Mucosal Response: An Ex-Vivo Organ Culture Model of Post-Infectious Irritable Bowel Syndrome

P.03.15: Lactobacillus Casei DG and its Postbiotic Reduce the Inflammatory Mucosal Response: An Ex-Vivo Organ Culture Model of Post-Infectious Irritable Bowel Syndrome

Antimicrobial effect of probiotics on bacterial species from dental plaque.

The antimicrobial role of probiotic Lactobacillus casei subspecies casei DG (L. casei DG) and of the mix culture of probiotic Lactobacillus acidophilus LA-5 and Bifidobacterium BB-12 was tested on species of Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera from supragingival sites from dogs with dental disease of different breed, age, sex, weight, and diet. The research was conducted on these four genera because of their importance in zoonotic infections after dog bites. Species from Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera were isolated and identified. To test the antimicrobial efficacy of L. casei DG and the mixed culture of probiotic L. acidophilus LA-5 and Bifidobacterium bifidum BB-12 on the pathogenic species, the agar overlay method was used. L. casei DG had a bactericidal effect on all analyzed species isolated from Staphylococcus, Streptococcus, Pasteurella, and Neisseria genera after 24 hours of incubation. The mixed probiotic culture made up of L. acidophilus LA-5 and Bifidobacterium BB-12 species had no bactericidal effect on the species of Staphylococcus and Streptococcus genera, which were resistant. However, it had a bacteriostatic effect on several species of Pasteurella and Neisseria genera. This work highlights the antimicrobial potential of probiotics in vitro, demonstrating that the probiotic L. casei DG has a bactericidal effect on all analyzed species isolated from dental plaque and that the mix culture of probiotic L. acidophilus LA-5 and Bifidobacterium BB-12 has only a bacteriostatic effect.

Low efficacy of levofloxacin-doxycycline-based third-line triple therapy for Helicobacter pylori eradication in Italy.

To evaluate a levofloxacin-doxycycline-based triple therapy with or without a susceptibility culture test in non-responders to Helicobacter pylori (H. pylori) eradication. A total of 142 (99 women, 43 men; mean 53.0 ± 12.7 years) non-responders to more than two H. pylori eradication therapies underwent susceptibility culture tests or were treated with a seven-day triple therapy consisting of esomeprazole, 20 mg b.i.d., levofloxacin, 500 mg b.i.d., and doxycycline, 100 mg b.i.d., randomly associated with (n = 71) or without (n = 71) Lactobacillus casei DG. H. pylori status was checked in all patients at enrollment and at least 8 wk after the end of therapy. Compliance and tolerability of regimens were also assessed. H. pylori eradication was achieved in < 50% of patients [per prototol (PP) = 49%; intention to treat (ITT) = 46%]. Eradication rate was higher in patients administered probiotics than in those without (PP = 55% vs 43%; ITT = 54% vs 40%). Estimated primary resistance to levofloxacin was 18% and multiple resistance was 31%. Therapy was well tolerated, and side effects were generally mild, with only one patient experiencing severe effects. Third-line levofloxacin-doxycycline triple therapy had a low H. pylori eradication efficacy, though the success and tolerability of this treatment may be enhanced with probiotics.

Sa1984 Probiotic and Postbiotic Effects of Lactobacillus Casei DG on Enteroglial-Derived S100B and Nitric Oxide Production in Human Intestinal Biopsies

Sa1984 Probiotic and Postbiotic Effects of Lactobacillus Casei DG on Enteroglial-Derived S100B and Nitric Oxide Production in Human Intestinal Biopsies

Scientific Opinion on the substantiation of health claims related to Lactobacillus casei DG CNCM I‐1572 and decreasing potentially pathogenic gastro intestinal microorganisms (ID 2949, 3061, further assessment) pursuant to Article 13(1) of Regulation (EC) No 1924/2006

Following a request from the European Commission, the Panel on Dietetic Products, Nutrition and Allergies was asked to provide a scientific opinion on a list of health claims pursuant to Article 13 of Regulation (EC) No 1924/2006 in the framework of further assessment related to Lactobacillus casei DG CNCM I-1572 and decreasing potentially pathogenic gastro-intestinal microorganisms. The food constituent that is the subject of the health claim, Lactobacillus casei DG CNCM I-1572, is sufficiently characterised. The claimed effect, decreasing potentially pathogenic gastro-intestinal microorganisms, might be a beneficial physiological effect. The proposed target population is the general population. No human studies were provided from which conclusions could be drawn for the scientific substantiation of the claim. On the basis of the data presented, the Panel concludes that a cause and effect relationship has not been established between the consumption of Lactobacillus casei DG CNCM I-1572 and decreasing potentially pathogenic gastro-intestinal microorganisms.

Rectal Administration of Lactobacillus casei DG Modifies Flora Composition and Toll-Like Receptor Expression in Colonic Mucosa of Patients with Mild Ulcerative Colitis

An imbalance in gut microbiota seems to contribute to the development of chronic inflammatory disorders of the gastrointestinal tract, such as ulcerative colitis (UC). Although it has been suggested that probiotic supplementation is an effective approach to colitis, its effects on intestinal flora and on mucosal cytokine balance have never been explored. To evaluate the effect of Lactobacillus casei (L.casei) DG, a probiotic strain, on colonic-associated microbiota, mucosal cytokine balance, and toll-like receptor (TLR) expression. Twenty-six patients with mild left-sided UC were randomly allocated to one of three groups for an 8-week treatment period: the first group of 7 patients received oral 5-aminosalicylic acid (5-ASA) alone, the second group of 8 patients received oral 5-ASA plus oral L.casei DG, and the third group of 11 patients received oral 5-ASA and rectal L.casei DG. Biopsies were collected from the sigmoid region to culture mucosal-associated microbes and to assess cytokine and TLR messenger RNA (mRNA) levels by quantitative real-time polymerase chain reaction (RT-PCR). 5-ASA alone or together with oral L.casei DG failed to affect colonic flora and TLR expression in a significant manner, but when coupled with rectally administered L.casei DG, it modified colonic microbiota by increasing Lactobacillus spp. and reducing Enterobacteriaceae. It also significantly reduced TLR-4 and interleukin (IL)-1β mRNA levels and significantly increased mucosal IL-10. Manipulation of mucosal microbiota by L.casei DG and its effects on the mucosal immune system seem to be required to mediate the beneficial activities of probiotics in UC patients.

In Vitro Screening of Probiotic Characteristics of Some Italian Products

Six commercial probiotic products produced and marketed Italy (containing Lactobacillus GG, Lactobacillus casei DG, Lactobacillus reuteri, Bacillus clausii spores, Bifidobacterium longum and Saccharomyces boulardii) were assayed for their stability during storage, acid, base and bile tolerance and adherence to human intestinal cells.Results indicate that storage, even at conditions established by manufacturers, affects the microbial content of products based on B. longum and partially of that containing L. casei GG. Differences in acid and bile tolerance were found for the products, S. boulardii being better able to survive acid and bile than bacteria. Vegetative cells of B. clausii and B. longum were more susceptible than lactobacilli to low pH values, while fewer differences were found for bile tolerance. Lactobacilli and only partially B. longum, were able to adhere to Caco-2 cells, while S. boulardii and B. clausii showed reduced adherence to human intestinal cells. In conclusion, the products did not completely fulfill all probiotic attributes.