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Evaluation of the Effect of Limosilactobacillus fermentum CECT5716 on Gastrointestinal Infections in Infants: A Systematic Review and Meta-Analysis.

ABSTRACT: Reducing the incidence of gastrointestinal infections (GIs) that occur at early stages to mitigate hospitalizations and treatments with adverse effects is a promising strategy for providing well-being to infants and their families. This systematic review and meta-analysis explores whether the early administration of Limosilactobacillus fermentum CECT5716 might be effective as a preventive therapy for GIs. We reviewed the literature to identify randomized controlled trials (RCTs) investigating the effectiveness of milk formulas supplemented with L. fermentum CECT5716 administered to infants at early stages to reduce the incidence of GIs. The MEDLINE (via PubMed), Web of Science (WoS), and Cochrane Central Register of Controlled Trials (via CENTRAL) databases were searched up to 15 June 2021. GI data from the included studies were synthesized in a random-effects model. Three RCTs were finally selected including 435 infants. There was a significant reduction in the incidence rate of GIs for those receiving L. fermentum CECT5716 compared with those receiving placebo (IRR: 0.52, 95% CI: 0.36-0.74, p = 0.0004). Heterogeneity between studies was moderate (I² = 54.5%). Based on the present systematic review and meta-analysis, the administration of L. fermentum CECT5716 at doses from 1 × 10⁹ to 8.4 × 10⁸ cfu/day in milk formulas may prevent GIs in infants up to 12 months old. Longer-term studies including a higher number of infants are needed to determine whether the use of this probiotic during the early stages of life is an efficient way to reduce the incidence of GIs.

SUBMITTER: Pastor-Villaescusa B

PROVIDER: S-EPMC8305821 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Candida glabrata is a human-associated opportunistic fungal pathogen. It shares its niche with Lactobacillus spp. in the gastrointestinal and vaginal tract. In fact, Lactobacillus species are thought to competitively prevent Candida overgrowth. We investigated the molecular aspects of this antifungal effect by analyzing the interaction of C. glabrata strains with Limosilactobacillus fermentum. From a collection of clinical C. glabrata isolates, we identified strains with different sensitivities to L. fermentum in coculture. We analyzed the variation of their expression pattern to isolate the specific response to L. fermentum. C. glabrata-L. fermentum coculture induced genes associated with ergosterol biosynthesis, weak acid stress, and drug/chemical stress. L. fermentum coculture depleted C. glabrata ergosterol. The reduction of ergosterol was dependent on the Lactobacillus species, even in coculture with different Candida species. We found a similar ergosterol-depleting effect with other lactobacillus strains (Lactobacillus crispatus and Lactobacillus rhamosus) on Candida albicans, Candida tropicalis, and Candida krusei. The addition of ergosterol improved C. glabrata growth in the coculture. Blocking ergosterol synthesis with fluconazole increased the susceptibility against L. fermentum, which was again mitigated by the addition of ergosterol. In accordance, a C. glabrata Δerg11 mutant, defective in ergosterol biosynthesis, was highly sensitive to L. fermentum. In conclusion, our analysis indicates an unexpected direct function of ergosterol for C. glabrata proliferation in coculture with L. fermentum. IMPORTANCE The yeast Candida glabrata, an opportunistic fungal pathogen, and the bacterium Limosilactobacillus fermentum both inhabit the human gastrointestinal and vaginal tract. Lactobacillus species, belonging to the healthy human microbiome, are thought to prevent C. glabrata infections. We investigated the antifungal effect of Limosilactobacillus fermentum on C. glabrata strains quantitively in vitro. The interaction between C. glabrata and L. fermentum evokes an upregulation of genes required for the synthesis of ergosterol, a sterol constituent of the fungal plasma membrane. We found a dramatic reduction of ergosterol in C. glabrata when it was exposed to L. fermentum. This effect extended to other Candida species and other Lactobacillus species. Furthermore, fungal growth was efficiently suppressed by a combination of L. fermentum and fluconazole, an antifungal drug which inhibits ergosterol synthesis. Thus, fungal ergosterol is a key metabolite for the suppression of C. glabrata by L. fermentum.

Project description:Applying probiotics to improve gut health and growth performance of pigs is considered an effective approach to reduce use of antimicrobial growth promoters in swine production. Understanding the properties of these probiotics is a prerequisite for the selection of probiotic strains for pigs. Host-adapted probiotic strains were suggested to exert probiotic effects by different mechanisms when compared to free-living or nomadic probiotic strains. This study assessed the effect of probiotic intervention with Limosilactobacillus reuteri TMW1.656, a host-adapted species producing the antimicrobial compound reutericyclin, its isogenic and reutericyclin-negative L. reuteri TMW1.656ΔrtcN, and with Limosilactobacillus fermentum and Lacticaseibacillus casei, two species with a nomadic lifestyle. Probiotic strains were supplemented to the post weaning diet in piglets by fermented feed or as freeze-dried cultures. The composition of fecal microbiota was determined by high throughput sequencing of 16S rRNA gene sequence tags; Enterotoxigenic Escherichia coli and Clostridium perfringens were quantified by qPCR targeting specific virulence factors. Inclusion of host-adapted L. reuteri effectively reduced ETEC abundance in swine intestine. In contrast, nomadic L. fermentum and L. casei did not show inhibitory effects on ETEC but reduced the abundance of Clostridium spp. In addition, the increasing abundance of Bacteriodetes after weaning was correlated to a reduction of ETEC abundance. Remarkably, the early colonization of piglets with ETEC was impacted by maternal-neonatal transmission; the pattern of virulence factors changed significantly over time after weaning. Probiotic intervention or the production of reutericyclin showed limited effect on the overall composition of commensal gut microbiota. In conclusion, the present study provided evidence that the lifestyle of lactobacilli is a relevant criterion for selection of probiotic cultures while the production of antimicrobial compounds has only minor effects.

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Evaluation of the Effect of Limosilactobacillus fermentum CECT5716 on Gastrointestinal Infections in Infants: A Systematic Review and Meta-Analysis.

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