CNCM I-745 Research Articles

Evaluation of synbiotic combinations of commercial probiotic strains with different prebiotics in in vitro and ex vivo human gut microcosm model.

Exploring probiotics for their crosstalk with the host microbiome through the fermentation of non-digestible dietary fibers (prebiotics) for their potential metabolic end-products, particularly short-chain fatty acids (SCFAs), is important for understanding the endogenous host-gut microbe interaction. This study was aimed at a systematic comparison of commercially available probiotics to understand their synergistic role with specific prebiotics in SCFAs production both in vitro and in the ex vivo gut microcosm model. Probiotic strains isolated from pharmacy products including Lactobacillus sporogenes (strain not labeled), Lactobacillus rhamnosus GG (ATCC53103), Streptococcus faecalis (T-110 JPC), Bacillus mesentericus (TO-AJPC), Bacillus clausii (SIN) and Saccharomyces boulardii (CNCM I-745) were assessed for their probiotic traits including survival, antibiotic susceptibility, and antibacterial activity against pathogenic strains. Our results showed that the microorganisms under study had strain-specific abilities to persist in human gastrointestinal conditions and varied anti-infective efficacy and antibiotic susceptibility. The probiotic strains displayed variation in the utilization of six different prebiotic substrates for their growth under aerobic and anaerobic conditions. Their prebiotic scores (PS) revealed which were the most suitable prebiotic carbohydrates for the growth of each strain and suggested xylooligosaccharide (XOS) was the poorest utilized among all. HPLC analysis revealed a versatile pattern of SCFAs produced as end-products of prebiotic fermentation by the strains which was influenced by growth conditions. Selected synbiotic (prebiotic and probiotic) combinations showing high PS and high total SCFAs production were tested in an ex vivo human gut microcosm model. Interestingly, significantly higher butyrate and propionate production was found only when synbiotics were applied as against when individual probiotic or prebiotics were applied alone. qRT-PCR analysis with specific primers showed that there was a significant increase in the abundance of lactobacilli and bifidobacteria with synbiotic blends compared to pre-, or probiotics alone. In conclusion, this work presents findings to suggest prebiotic combinations with different well-established probiotic strains that may be useful for developing effective synbiotic blends.

Multifactorial inhibition of Candida albicans by combinations of lactobacilli and probiotic Saccharomyces cerevisiae CNCM I-3856

Strategies against the opportunistic fungal pathogen Candida albicans based on probiotic microorganisms represent a promising alternative to traditional antifungals. Here, we investigated the effects of Lactobacillaceae isolates from fermented foods or the human vagina, alone or in combination with the probiotic yeast Saccharomyces cerevisiae CNCM I-3856, against C. albicans in vitro. Nine out of nineteen tested strains of Lactobacillaceae inhibited growth of C. albicans with inhibition zones of 1–3 mm in spot assays. Five out of nineteen lactobacilli tested as such or in combination with S. cerevisiae CNCM I-3856 also significantly inhibited C. albicans hyphae formation, including Limosilactobacillus fermentum LS4 and L. fermentum LS5 resulting in respectively 62% and 78% hyphae inhibition compared to the control. Thirteen of the tested nineteen lactobacilli aggregated with the yeast form of C. albicans, with Lactiplantibacillus carotarum AMBF275 showing the strongest aggregation. The aggregation was enhanced when lactobacilli were combined with S. cerevisiae CNCM I-3856. No significant antagonistic effects were observed between the tested lactobacilli and S. cerevisiae CNCM I-3856. The multifactorial activity of Lactobacillaceae strains alone or combined with the probiotic S. cerevisiae CNCM I-3856 against C. albicans without antagonistic effects between the beneficial strains, paves the way for developing consortium probiotics for in vivo applications.

Outcome-Specific Efficacy of Different Probiotic Strains and Mixtures in Irritable Bowel Syndrome: A Systematic Review and Network Meta-Analysis.

Irritable bowel syndrome (IBS) is a common gastrointestinal disease. The efficacy of different probiotics in treating IBS remains controversial. This network meta-analysis aimed to compare and rank the outcome-specific efficacy of different probiotic strains or combinations in adults with IBS. We searched the literature up to June 2023. Randomized controlled trials (RCTs) that evaluated the efficacy of probiotics in IBS were included. A frequentist framework was used to perform this study. In total, 9253 participants from 81 RCTs were included in the study. Four probiotic strains and five mixtures were significantly superior to placebo in improving IBS Symptom Severity Scale, among which Lactobacillus acidophilus DDS-1 ranked first (surface under the cumulative ranking, SUCRA, 92.9%). A mixture containing five probiotics (SUCRA, 100%) ranked first in improving the IBS-Quality of life. Bacillus coagulans MTCC 5856 (SUCRA, 96.9%) and Bacillus coagulans Unique IS2 (SUCRA, 92.6%) were among the most effective probiotics for improving abdominal pain. Three probiotic strains and two mixtures were effective in alleviating abdominal bloating. Four probiotic strains and a mixture were significantly superior to placebo in reducing the bowel movement frequency in diarrhea-predominant IBS (IBS-D). Bacillus coagulans MTCC 5856 (SUCRA, 99.6%) and Saccharomyces cerevisiae CNCM I-3856 (SUCRA, 89.7%) were among the most effective probiotics for improving the Bristol stool form scale of IBS-D. Only some probiotics are effective for particular outcomes in IBS patients. This study provided the first ranking of outcome-specific efficacy of different probiotic strains and combinations in IBS. Further studies are needed to confirm these results.

L. rhamnosus CNCM I-3690 survival, adaptation, and small bowel microbiome impact in human

ABSTRACT Fermented foods and beverages are a significant source of dietary bacteria that enter the gastrointestinal (GI) tract. However, little is known about how these microbes survive and adapt to the small intestinal environment. Colony-forming units (CFU) enumeration and viability qPCR of Lacticaseibacillus rhamnosus CNCM I-3690 in the ileal effluent of 10 ileostomy subjects during 12-h post consumption of a dairy product fermented with this strain demonstrated the high level of survival of this strain during human small intestine passage. Metatranscriptome analyses revealed the in situ transcriptome of L. rhamnosus in the small intestine, which was contrasted with transcriptome data obtained from in vitro cultivation. These comparative analyses revealed substantial metabolic adaptations of L. rhamnosus during small intestine transit, including adjustments of carbohydrate metabolism, surface-protein expression, and translation machinery. The prominent presence of L. rhamnosus in the effluent samples did not elicit an appreciable effect on the composition of the endogenous small intestine microbiome, but significantly altered the ecosystem’s overall activity profile, particularly of pathways associated with carbohydrate metabolism. Strikingly, two of the previously recognized gut-brain metabolic modules expressed in situ by L. rhamnosus (inositol degradation and glutamate synthesis II) are among the most dominantly enriched activities in the ecosystem’s activity profile. This study establishes the survival capacity of L. rhamnosus in the human small intestine and highlights its functional adjustment in situ, which we postulate to play a role in the probiotic effects associated with this strain.

Over-production of exopolysaccharide by Lacticaseibacillus rhamnosus CNCM I-3690 strain cutbacks its beneficial effect on the host

Most lactobacilli produce extracellular polysaccharides that are considered to contribute to the probiotic effect of many strains. Lacticaseibacillus rhamnosus CNCM I-3690 is an anti-inflammatory strain able to counterbalance gut barrier dysfunction. In this study ten spontaneous variants of CNCM I-3690 with different EPS-production were generated and characterized by their ropy phenotype, the quantification of the secreted EPS and genetic analysis. Amongst them, two were further analysed in vitro and in vivo: an EPS over-producer (7292) and a low-producer derivative of 7292 (7358, with similar EPS levels than the wild type (WT) strain). Our results showed that 7292 does not have anti-inflammatory profile in vitro, and lost the capacity to adhere to the colonic epithelial cells as well as the protective effect on the permeability. Finally, 7292 lost the protective effects of the WT strain in a murine model of gut dysfunction. Notably, strain 7292 was unable to stimulate goblet cell mucus production and colonic IL-10 production, all key features for the beneficial effect of the WT strain. Furthermore, transcriptome analysis of colonic samples from 7292-treated mice showed a down-regulation of anti-inflammatory genes. Altogether, our results point out that the increase of EPS production in CNCM I-3690 impairs its protective effects and highlight the importance of the correct EPS synthesis for the beneficial effects of this strain.

Endogenous small intestinal microbiome determinants of transient colonisation efficiency by bacteria from fermented dairy products: a randomised controlled trial

BackgroundThe effects of fermented food consumption on the small intestine microbiome and its role on host homeostasis are largely uncharacterised as our knowledge on intestinal microbiota relies mainly on faecal samples analysis. We investigated changes in small intestinal microbial composition and functionality, short chain fatty acid (SCFA) profiles, and on gastro-intestinal (GI) permeability in ileostomy subjects upon the consumption of fermented milk products.ResultsWe report the results from a randomised, cross-over, explorative study where 16 ileostomy subjects underwent 3, 2-week intervention periods. In each period, they consumed either milk fermented by Lacticaseibacillus rhamnosus CNCM I-3690, or milk fermented by Streptococcus thermophilus CNCM I-1630 and Lactobacillus delbrueckii subsp. bulgaricus CNCM I-1519, or a chemically acidified milk (placebo) daily. We performed metataxonomic, metatranscriptomic analysis, and SCFA profiling of ileostomy effluents as well as a sugar permeability test to investigate the microbiome impact of these interventions and their potential effect on mucosal barrier function. Consumption of the intervention products impacted the overall small intestinal microbiome composition and functionality, mainly due to the introduction of the product-derived bacteria that reach in several samples 50% of the total microbial community. The interventions did not affect the SCFA levels in ileostoma effluent, or gastro-intestinal permeability and the effects on the endogenous microbial community were negligible. The impact on microbiome composition was highly personalised, and we identified the poorly characterised bacterial family, Peptostreptococcaceae, to be positively associated with a low abundance of the ingested bacteria. Activity profiling of the microbiota revealed that carbon- versus amino acid-derived energy metabolism of the endogenous microbiome could be responsible for the individual-specific intervention effects on the small intestine microbiome composition and function, reflected also on urine microbial metabolites generated through proteolytic fermentation.ConclusionsThe ingested bacteria are the main drivers of the intervention effect on the small intestinal microbiota composition. Their transient abundance level is highly personalised and influenced by the energy metabolism of the ecosystem that is reflected by its microbial composition (http://www.clinicaltrials.gov, ID NCT NCT02920294).3z8GaJs8-4AmNdyX8busiEVideo

Saccharomyces cerevisiae prevents postoperative recurrence of Crohn's disease modeled by ileocecal resection in HLA-B27 transgenic rats

Postoperative recurrence (POR) after ileocecal resection (ICR) affects most Crohn's disease patients within 3-5 years after surgery. Adherent-invasive Escherichia coli (AIEC) typified by the LF82 strain are pathobionts that are frequently detected in POR of Crohn's disease and have a potential role in the early stages of the disease pathogenesis. Saccharomyces cerevisiae CNCM I-3856 is a probiotic yeast reported to inhibit AIEC adhesion to intestinal epithelial cells and to favor their elimination from the gut. To evaluate the efficacy of CNCM I-3856 in preventing POR induced by LF82 in an HLA-B27 transgenic (TgB27) rat model. Sixty-four rats [strain F344, 38 TgB27, 26 control non-Tg (nTg)] underwent an ICR at the 12th wk (W12) of life and were sacrificed at the 18th wk (W18) of life. TgB27 rats were challenged daily with oral administration of LF82 (109 colony forming units (CFUs)/day (d), n = 8), PBS (n = 5), CNCM I-3856 (109 CFUs/d, n = 7) or a combination of LF82 and CNCM I-3856 (n = 18). nTg rats receiving LF82 (n = 5), PBS (n = 5), CNCM I-3856 (n = 7) or CNCM I-3856 and LF82 (n = 9) under the same conditions were used as controls. POR was analyzed using macroscopic (from 0 to 4) and histologic (from 0 to 6) scores. Luminal LF82 quantifications were performed weekly for each animal. Adherent LF82 and inflammatory/regulatory cytokines were quantified in biopsies at W12 and W18. Data are expressed as the median with the interquartile range. nTg animals did not develop POR. A total of 7/8 (87%) of the TgB27 rats receiving LF82 alone had POR (macroscopic score ≥ 2), which was significantly prevented by CNCM I-3856 administration [6/18 (33%) TgB27 rats, P = 0.01]. Macroscopic lesions were located 2 cm above the anastomosis in the TgB27 rats receiving LF82 alone and consisted of ulcerations with a score of 3.5 (2 - 4). Seven out of 18 TgB27 rats (39%) receiving CNCM I-3856 and LF82 had no macroscopic lesions. Compared to untreated TgB27 animals receiving LF82 alone, coadministration of CNCM I-3856 and LF82 significantly reduced the macroscopic [3.5 (2 - 4) vs 1 (0 - 3), P = 0.002] and histological lesions by more than 50% [4.5 (3.3 - 5.8) vs 2 (1.3 - 3), P = 0.003]. The levels of adherent LF82 were correlated with anastomotic macroscopic scores in TgB27 rats (r = 0.49, P = 0.006), with a higher risk of POR in animals having high levels of luminal LF82 (71.4% vs 25%, P = 0.02). Administration of CNCM I-3856 significantly reduced the levels of luminal and adherent LF82, increased the production of interleukin (IL)-10 and decreased the production of IL-23 and IL-17 in TgB27 rats. In a reliable model of POR induced by LF82 in TgB27 rats, CNCM I-3856 prevents macroscopic POR by decreasing LF82 infection and gut inflammation.

Improved gut microbiome recovery following drug therapy is linked to abundance and replication of probiotic strains

ABSTRACT Probiotics have been used for decades to alleviate the negative side-effects of oral antibiotics, but our mechanistic understanding on how they work is so far incomplete. Here, we performed a metagenomic analysis of the fecal microbiota in participants who underwent a 14-d Helicobacter pylori eradication therapy with or without consumption of a multi-strain probiotic intervention (L. paracasei CNCM I-1518, L. paracasei CNCM I-3689, L. rhamnosus CNCM I-3690, and four yogurt strains) in a randomized, double-blinded, controlled clinical trial. Using a strain-level analysis for detection and metagenomic determination of replication rate, ingested strains were detected and replicated transiently in fecal samples and in the gut during and following antibiotic administration. Consumption of the fermented milk product led to a significant, although modest, improvement in the recovery of microbiota composition. Stratification of participants into two groups based on the degree to which their microbiome recovered showed i) a higher fecal abundance of the probiotic L. paracasei and L. rhamnosus strains and ii) an elevated replication rate of one strain (L. paracasei CNCMI-1518) in the recovery group. Collectively, our findings show a small but measurable benefit of a fermented milk product on microbiome recovery after antibiotics, which was linked to the detection and replication of specific probiotic strains. Such functional insight can form the basis for the development of probiotic-based intervention aimed to protect gut microbiome from drug treatments.

Lactobacillus rhamnosus CNCM I-3690 decreases subjective academic stress in healthy adults: a randomized placebo-controlled trial

ABSTRACT Psychological stress negatively affects the intestinal barrier function in animals and humans. We aimed to study the effect of Lactobacillus rhamnosus CNCM I-3690 on intestinal permeability and stress-markers during public speech. Healthy students were randomized to L. rhamnosus-containing (test) or acidified (placebo) milk consumed twice daily for 4 weeks, with 46 subjects per treatment group. Small intestinal permeability was quantified by a 2 h urinary lactulose–mannitol ratio (LMR, primary outcome), fractional excretion of lactulose (FEL) and mannitol (FEM). Salivary cortisol, State-Trait Anxiety Inventory (STAI) and Perceived Stress scores (PSS) were collected. No between-treatment differences were found for LMR (p = .71), FEL or FEM. Within-treatment analyses showed similar LMR and FEL but a stress-induced increase of FEM with the placebo (p < .05) but not test product. Despite a similar increase in salivary cortisol, the stress-induced increase in STAI was significantly lower with the test product vs. placebo (p = .01). Moreover, a stress-preventative effect of the probiotic was found for PSS and more pronounced in subjects with high stress-induced cortisol (p = .01). While increased FEM was mediated by salivary cortisol levels, the effect of the test product on subjective stress was not mediated by changes in FEM. No serious adverse events occurred. In conclusion, we demonstrated that L. rhamnosus CNCM I-3690 prevented stress-induced hyperpermeability to mannitol. Subjective but not objective stress-markers were reduced with L. rhamnosus vs. placebo, suggesting anxiolytic effects, which were independent of barrier stabilization and attractive for the reduction of stress in both health and disease. Clinicaltrials.gov, number NCT03408691.

Biovalorization of Market Surplus Bread for Development of Probiotic-Fermented Potential Functional Beverages.

Bread wastage is a growing concern in many developed countries. This research aimed to explore the biovalorization of market surplus bread for the development of probiotic-fermented beverages in a zero-waste approach. Bread slurries with different initial total solid contents were inoculated with probiotics Lacticaseibacillus rhamnosus GG (LGG) and Saccharomyces cerevisiae CNCM I-3856, alone and in combination. Our results showed that, of all percentages tested, 5% (w/w, dry weight) initial total solid content resulted in better growth of the probiotics and higher cell counts, while the texture of bread slurries with concentrations higher than 5.0% was too thick and viscous for bread beverage developments. In addition, the development of probiotic-fermented bread beverages was feasible on various types of bread. Furthermore, food additives (sweetener and stabilizer) did not affect the growth of LGG and S. cerevisiae CNCM I-3856 in both mono- and co-culture fermentation. During shelf life measurement, co-inoculation of LGG with S. cerevisiae CNCM I-3856 significantly improved the survival of LGG compared to the mono-culture at 5 and 30 °C, demonstrating the protective effects provided by the yeast. Our study suggests the potential of using market surplus bread as raw materials to deliver live probiotics with sufficient cell counts.

Targeted and Nontargeted Metabolomics of Amino Acids and Bioactive Metabolites in Probiotic-Fermented Unhopped Beers Using Liquid Chromatography High-Resolution Mass Spectrometry.

Beer is one of the most popular beverages in the world. The increased popularity of craft beers has led to the development of unique beers that are alcohol-free, gluten-free, low calorie, or with functional properties through fermentation with probiotic microorganisms. In this study, functional unhopped beers were evaluated by utilizing probiotics (Lacticaseibacillus paracasei Lpc-37 and ibSium Saccharomyces cerevisiae CNCM I-3856) as starter cultures. The metabolites produced by probiotics were investigated using a nontargeted metabolomics approach and identified against metabolomics databases (Kyoto Encyclopedia of Genes and Genomes (KEGG), Human Metabolome Database (HMDB), Yeast Metabolome Database (YMDB), METLIN tandem mass spectrometry (MS/MS)). Derivatives of branched-chain (leucine) and aromatic amino acids (phenylalanine, tryptophan, and tyrosine) were enriched (one-way analysis of variance (ANOVA) p < 0.05) in probiotic-fermented unhopped beers, especially tryptophan metabolites. In addition, the synergistic effects of yeast-lactic acid bacteria (LAB) interactions led to further enrichment of higher acids such as (S)-(-)-2-hydroxyisocaproic acid, phenyllactic acid, hydroxyphenyllactic acid, and indolelactic acid. The potential pathways for the formation of novel bioactive tryptophan metabolites (indole and indoleacrylic acid) by LAB were elucidated. Altogether, probiotic LAB-fermented unhopped beer showed the highest antioxidant capacity and total phenolic content. This work provides the basis for the discovery of bioactive metabolites in probiotic-fermented foods.

Strain-specific and outcome-specific efficacy of probiotics for the treatment of irritable bowel syndrome: A systematic review and meta-analysis.

BackgroundConsistent guidance for choosing an appropriate probiotic for the treatment of irritable bowel syndrome is lacking.MethodsLiterature databases searched included: PubMed, Google Scholar and NIH registry of clinical trials from inception to June 2021. Inclusion criteria: randomized controlled trials (RCTs) enrolling adult or pediatric IBS patients comparing probiotics against controls and ≥ 2 RCTs with common IBS outcome measures within each type of probiotic. Five common measures of IBS symptoms (changes in global Irritable Bowel Syndrome Severity Scoring System or IBS-SSS scores, frequency of global responders, changes in bloating or abdominal pain scores and frequency of abdominal pain relief) were used. This study was registered at Prospero (#CRD42018109169).FindingsWe screened 521 studies and included 42 randomized controlled trials (45 treatment arms, N = 3856). Four probiotics demonstrated significant reduction in abdominal pain relief: B. coagulans MTCC5260 (RR= 4.9, 95% C.I. 3.3, 7.3), L. plantarum 299v (RR= 4.6, 95% CI 1.9, 11.0), S. boulardii CNCM I-745 (RR= 1.5, 95% C.I. 1.1, 2.1) and S. cerevisiae CNCM I-3856 (RR= 1.3, 95% C.I. 1.04, 1.6). Mild-moderate adverse events were reported in 51% of the trials, none were more associated with the probiotic compared to controls.InterpretationAlthough the analysis of probiotic efficacy was limited by the diversity of IBS outcomes used in trials and lack of confirmatory trials for some strains, six single-strain probiotics and three different types of probiotic mixtures showed significant efficacy for at least one IBS outcome measure. These results might be relevant to clinical practice and policy.

Bioprocess optimization of glutathione production by Saccharomyces boulardii: biochemical characterization of glutathione peroxidase.

The well-known probiotic GRAS Saccharomyces boulardii (CNCM I-745) was used for the first time to produce glutathione (GSH). The culture conditions affecting GSH biosynthesis were screened using a Plackett-Burman design (PBD). Analyzing the regression coefficients for 12 tested variables, yeast extract, glucose, peptone, cysteine, temperature and agitation rate had a positive significant effect on GSH production with a maximum yeild 192mg/L. The impact of kinetics of adding cysteine was investigated in 19 experiments during the growth time course (0-36h), and the maximum yield of glutathione (235mg/L) was obtained by addition of cysteine after 8h post-inoculation. The most significant variables were further explored at five levels using central composite rotatable design (CCRD), giving a maximum production of GSH (552mg/L). Using baffled flasks, the yield of GSH was increased to 730mg/L, i.e., 1.32-fold increment. The two rate-limiting genes of GSH biosynthesis "γ-glutamyl cysteine synthetase (GSH1) and GSH-synthetase (GSH2)" were amplified and sequenced to validate the GSH biosynthetic potency of S. boulardii. The sequences of genes showed 99% similarity with GSH1 and GSH2 genes of S. cerevisiae. Glutathione peroxidase was purified and characterized from S. boulardii with molecular mass and subunit structure of 80kDa and 35kDa as revealed from native and SDS-PAGE, ensuring its homodimeric identity. The activity of GPx was reduced by 2.5-fold upon demetallization confirming its metalloproteinic identity. The GPx was strongly inhibited by hydroxylamine and DTNB, ensuring the implication of surface lysine and cysteine residues on the enzyme active site domains.

A Randomised, Controlled Trial: Effect of a Multi-Strain Fermented Milk on the Gut Microbiota Recovery after Helicobacter pylori Therapy.

Helicobacter pylori (Hp) eradication therapy alters gut microbiota, provoking gastrointestinal (GI) symptoms that could be improved by probiotics. The study aim was to assess the effect in Hp patients of a Test fermented milk containing yogurt and Lacticaseibacillus (L. paracasei CNCM I-1518 and I-3689, L. rhamnosus CNCM I-3690) strains on antibiotic associated diarrhea (AAD) (primary aim), GI-symptoms, gut microbiota, and metabolites. A randomised, double-blind, controlled trial was performed on 136 adults under 14-day Hp treatment, receiving the Test or Control product for 28 days. AAD and GI-symptoms were reported and feces analysed for relative and quantitative gut microbiome composition, short chain fatty acids (SCFA), and calprotectin concentrations, and viability of ingested strains. No effect of Test product was observed on AAD or GI-symptoms. Hp treatment induced a significant alteration in bacterial and fungal composition, a decrease of bacterial count and alpha-diversity, an increase of Candida and calprotectin, and a decrease of SCFA concentrations. Following Hp treatment, in the Test as compared to Control group, intra-subject beta-diversity distance from baseline was lower (padj = 0.02), some Enterobacteriaceae, including Escherichia-Shigella (padj = 0.0082) and Klebsiella (padj = 0.013), were less abundant, and concentrations of major SCFA (p = 0.035) and valerate (p = 0.045) were higher. Viable Lacticaseibacillus strains were detected during product consumption in feces. Results suggest that, in patients under Hp treatment, the consumption of a multi-strain fermented milk can induce a modest but significant faster recovery of the microbiota composition (beta-diversity) and of SCFA production and limit the increase of potentially pathogenic bacteria.

Heteropolysaccharides from S. cerevisiae show anti-adhesive properties against E. coli associated with Crohn's disease

The Saccharomyces cerevisiae CNCM I-3856 was previously reported to strongly inhibit adherent-invasive Escherichia coli (AIEC) adhesion to intestinal epithelial cells in vitro and to favor AIEC elimination from the gut in a murine model of Crohn's disease in vivo. In order to identify which cell wall components of yeast are responsible for AIEC elimination, constituent polysaccharides of yeast were isolated and their anti-adhesive ability against AIEC adhesion in vitro was screened. A fraction containing mannan, β-glucan and α-glucan extracted from yeast cell-walls was shown to inhibit 95% of AIEC adhesion in vitro and was thus identified as the strongest anti-adhesive yeast cell wall component. Furthermore, this mannan-glucan-containing fraction was shown to accelerate AIEC decolonization from gut in vivo. This fraction could be proposed as a treatment to eliminate AIEC bacteria in patients with Crohn's disease, a microbial trigger of intestinal inflammation.

Probiotics for the Prevention of Acute Respiratory-Tract Infections in Older People: Systematic Review.

The aim of this systematic review was to present the indirect influence of probiotics on the incidence and duration of acute upper respiratory-tract infections in older people, by regulating the immune system. Eight randomized, placebo-controlled clinical trials met the inclusion criteria, considering the threshold of older people being 60 years and over. Single strain probiotics were used in all studies, including three probiotic strains used in fermented foods: Lactobacillus delbrueckii subsp. bulgaricus OLL1073R-1, Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 and Lacticaseibacillus paracasei Shirota, and three probiotic strains used as food supplements: Loigolactobacillus coryniformis K8 CECT5711, Bacillus subtilis CU1 and Lacticaseibacillus rhamnosus GG. Current evidence showed that certain probiotic strains were better than a placebo in lowering the incidence or number of older people experiencing acute upper respiratory tract infections; however, not all probiotic strains were efficient, and not all studies reported statistically significant outcomes. More high quality large-scale properly controlled clinical studies focusing on older people are warranted.

Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 Modulate Macrophage Gene Expression and Ameliorate Damage Markers in the Liver of Zucker-Lepr fa/fa Rats.

Non-alcoholic fatty liver disease (NAFLD) has reached pandemic proportions worldwide. We have previously reported that the probiotic strains Bifidobacterium breve CNCM I-4035, Lactobacillus paracasei CNCM I-4034 and Lactobacillus rhamnosus CNCM I-4036 exert anti-inflammatory effects in the intestine of Zucker-Leprfa/fa rats. In this work, we focused on their hepatic effects. M1 macrophages are related to inflammation and NAFLD pathogenesis, whereas M2 macrophages release anti-inflammatory mediators. We evaluated the effects of these 3 strains on macrophage polarization, inflammation and liver damage of Zucker-Leprfa/fa rats. The animals received either a placebo or 1010 CFU of probiotics orally for 30 days. Nos2 and Cd86 mRNA levels were determined as markers of M1 macrophages, and Cd163 and Arg1 as M2 markers, respectively, by qRT-PCR. Liver damage was determined by lipid peroxidation, leukocyte infiltration and myeloperoxidase activity. We evaluated a panoply of circulating chemokines, the hepatic ratio P-Akt/Akt, NF-kB and P-NF-kB protein levels. All 3 probiotic strains modulated macrophage polarization in liver and circulating levels of inflammation-related mediators. L. paracasei CNCM I-4034 increased the ratio P-Akt/Akt and NF-kB protein levels. B. breve CNCM I-4035, L. paracasei CNCM I-4034 and L. rhamnosus CNCM I-4036 decreased both pro-inflammatory macrophage gene expression and leukocyte infiltration in the liver.

Strain-Specific and Outcome-Specific Efficacy of Probiotics for the Treatment of Irritable Bowel Syndrome:&amp;nbsp;A Systematic Review and Meta-Analysis

Background: Consistent guidance for choosing an appropriate probiotic for the treatment of irritable bowel syndrome is lacking. Methods: A literature search of databases (PubMed, Google Scholar and NIH registry of clinical trials) were searched from inception to June 2021. Inclusion criteria: randomized controlled trials enrolling adult or pediatric IBS patients comparing probiotics against controls, >2 RCTs with common IBS outcome measures within each type of probiotic. Five common measures of IBS symptoms (changes in global IBS-SSS scores, frequency of global responders, changes in bloating or abdominal pain scores and frequency of abdominal pain relief) were used. Findings: We screened 521 studies and included 42 randomized controlled trials (45 treatment arms, N=3856). Four probiotics demonstrated significant reduction in abdominal pain relief: B. coagulans MTCC5260 (RR=4.9, 95% C.I. 3.3, 7.3), L. plantarum 299v (RR=4.6, 95% CI 1.9, 11.0), S. boulardii CNCMI-745 (RR=1.5, 95% C.I. 1.1, 2.1) and S. cerevisiae CNCM I-3856 (RR=1.3, 95% C.I. 1.04, 1.6). Mild-moderate adverse events were reported in 51% of the trials, none were more associated with the probiotic compared to controls. Interpretation: Although the analysis of probiotics was limited by the diversity of IBS outcomes used in trials, six single-strain probiotics and three different types of probiotic mixtures showed significant efficacy for at least one IBS outcome measure. It is now possible to identify specific probiotics that are effective for IBS patients. Funding: None to declare. Declaration of Interest: LVM is on the Scientific Advisory Board of Bio-K+ (Bio-K PLUS, Canada) and on the Biocodex Microbiome Board (Biocodex, France) and is a paid lecturer for Bio-K+ and Biocodex. None of the authors own stock or equity in any of these companies. TK and AK declared no conflicts of interest.

Multi-targeted properties of the probiotic saccharomyces cerevisiae CNCM I-3856 against enterotoxigenic escherichia coli (ETEC) H10407 pathogenesis across human gut models

ABSTRACT Enterotoxigenic Escherichia coli (ETEC) is one of the most common causes of acute traveler’s diarrhea. Adhesins and enterotoxins constitute the major ETEC virulence traits. With the dramatic increase in antibiotic resistance, probiotics are considered a wholesome alternative to prevent or treat ETEC infections. Here, we examined the antimicrobial properties of the probiotic Saccharomyces cerevisiae CNCM I-3856 against ETEC H10407 pathogenesis upon co-administration in the TNO gastrointestinal Model (TIM-1), simulating the physicochemical and enzymatic conditions of the human upper digestive tract and preventive treatment in the Mucosal Simulator of the Human Intestinal Microbial Ecosystem (M-SHIME), integrating microbial populations of the ileum and ascending colon. Interindividual variability was assessed by separate M-SHIME experiments with microbiota from six human individuals. The probiotic did not affect ETEC survival along the digestive tract. However, ETEC pathogenicity was significantly reduced: enterotoxin encoding virulence genes were repressed, especially in the TIM-1 system, and a lower enterotoxin production was noted. M-SHIME experiments revealed that 18-days probiotic treatment stimulate the growth of Bifidobacterium and Lactobacillus in different gut regions (mucosal and luminal, ileum and ascending colon) while a stronger metabolic activity was noted in terms of short-chain fatty acids (acetate, propionate, and butyrate) and ethanol production. Moreover, the probiotic pre-treated microbiota displayed a higher robustness in composition following ETEC challenge compared to the control condition. We thus demonstrated the multi-inhibitory properties of the probiotic S. cerevisiae CNCM I-3856 against ETEC in the overall simulated human digestive tract, regardless of the inherent variability across individuals in the M-SHIME.

Effects of a Fermented Dairy Drink Containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (Lactobacillus casei CNCM I-1518) and the Standard Yogurt Cultures on the Incidence, Duration, and Severity of Common Infectious Diseases: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

There is considerable interest in the role of probiotics in immune function. The objective of this systematic review and meta-analysis was to assess the effects of the consumption of a fermented dairy drink containing Lacticaseibacillus paracasei subsp. paracasei CNCM I-1518 (the previous taxonomic nomenclature was Lactobacillus casei CNCM I-1518, prior to the nomenclature change in April 2020) and the standard yogurt cultures (hereinafter referred to collectively as “FDD”) on common infectious diseases (CIDs) in generally healthy children and adults. Nine literature databases were searched, and nine randomized controlled trials from eight publications were eligible for inclusion. Combined effect sizes were determined for three metrics of CID incidence, two metrics of CID duration, and one metric of CID severity. Compared to the control, the consumption of the FDD resulted in (1) a significant reduction in the odds of experiencing ≥1 CID (odds ratio (OR) (with a 95% confidence interval (CI)): 0.81 (0.66, 0.98); p = 0.029); (2) a significant reduction in mean CIDs per subject (−0.09 (−0.15, −0.04); p = 0.001); and (3) a trend towards reduced risk in cumulative CIDs (relative risk (RR): 0.91 (0.82, 1.01); p = 0.082). The consumption of the FDD had no significant effect on CID duration or severity. Based on the studies conducted thus far, these results suggest that the FDD may reduce CID incidence in the general population.