Studies of probiotics, fructan-type prebiotics, and synbiotics in patients with ulcerative colitis (UC) show significant heterogeneity in methodology and results. Here, we study the efficacy of such interventions and the reasons for the heterogeneity of their results. Eligible random controlled trials were collected from the PUBMED and SCOPUS databases. A total of 18 placebo-controlled and active treatment-controlled (i.e., mesalazine) studies were selected with a Jadad score ≥ 3, including 1491 patients with UC. Data for prebiotics and synbiotics were sparse and consequently these studies were excluded from the meta-analysis. The UC remission efficacy of probiotics was measured in terms of relative risk (RR) and odds ratio (OR). Significant effects were observed in patients with active UC whenever probiotics containing bifidobacteria were used, or when adopting the US Food and Drug Administration (FDA)-recommended scales (UC Disease Activity Index and Disease Activity Index). By the FDA recommended scales, the RR was 1.55 (CI95%: 1.13–2.15, p-value = 0.007, I2 = 29%); for bifidobacteria-containing probiotics, the RR was 1.73 (CI95%: 1.23–2.43, p-value = 0.002, I2 = 35%). No significant effects were observed on the maintenance of remission for placebo-controlled or mesalazine-controlled studies. We conclude that a validated scale is necessary to determine the state of patients with UC. However, probiotics containing bifidobacteria are promising for the treatment of active UC.

Prebiotic supplements are used to promote gastrointestinal health by stimulating beneficial bacteria. The aim of this study was to compare the potential prebiotic effects of fructans with increasing degrees of polymerization, namely fructooligosaccharides (FOS) and inulins with a low and high polymerization degree (LPDI and HPDI, respectively), using an ex vivo fermentation system to simulate the colonic environment. The system was inoculated with pooled feces from three healthy donors with the same baseline enterotype. Changes in microbiota composition were measured by 16S metagenomic sequencing after 2, 7, and 14 days of fermentation, and acid production was measured throughout the experiment. Alpha-diversity decreased upon inoculation of the ex vivo fermentation under all treatments. Composition changed significantly across both treatments and time (ANOSIM p < 0.005 for both factors). HPDI and LPDI seemed to be similar to each other regarding composition and acidification activity, but different from the control and FOS. FOS differed from the control in terms of composition but not acidification. HDPI restored alpha-diversity on day 14 as compared to the control (Bonferroni p < 0.05). In conclusion, the prebiotic activity of fructans appears to depend on the degree of polymerization, with LPDI and especially HPDI having a greater effect than FOS.

Functional gastrointestinal disorders (FGIDs) are a common concern during the first year of life. Recognized as gut-brain axis disorders by Rome IV criteria, FGIDs etiology is linked to altered gut-brain interaction, intestinal physiology, and microbiota. In this regard, probiotics have emerged as a promising therapy for infant FGIDs. In this study, we have investigated the probiotic potential of the strains Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041—isolated from healthy children’s feces—in the treatment of FGIDs. To this scope, genome sequences of both strains were obtained and subjected to in silico analyses. No virulence factors were detected for any strain and only the non-transferable erm(49) gene, which confers resistance to erythromycin and clindamycin, was identified in the genome of B. longum KABP042. Safety of both strains was confirmed by acute oral toxicity in rats. In vitro characterization revealed that the strains tolerate gastric and bile challenges and display a great adhesion capacity to human intestinal cells. The two strains mediate adhesion by different mechanisms and, when combined, synergically induce the expression of Caco-2 tight junction proteins. Moreover, growth inhibition experiments demonstrated the ability of the two strains alone and in combination to antagonize diverse Gram-negative and Gram-positive bacterial pathogens during sessile and planktonic growth. Pathogens’ inhibition was mostly mediated by the production of organic acids, but neutralization experiments strongly suggested the presence of additional antimicrobial compounds in probiotic culture supernatants such as the bacteriocin Lantibiotic B, whose gene was detected in the genome of B. longum KABP042. Finally, an exploratory, observational, pilot study involving 36 infants diagnosed with at least one FGID (infant colic and/or functional constipation) showed the probiotic formula was well tolerated and FGID severity was significantly reduced after 14 days of treatment with the 2 strains. Overall, this work provides evidence of the probiotic and synergic properties of strains B. longum KABP042 and P. pentosaceus KABP041, and of their potential to treat pediatric FGIDs.Clinical Trial Registration: [www.ClinicalTrials.gov], [identifier NCT04944628].

Introduction The pathophysiology of Irritable Bowel Syndrome (IBS) involves increased intestinal permeability, micro‐inflammation and gut dysbiosis with associated visceral hypersensitivity. The probiotic mix of Lactobacillus plantarum strains CECT7484 (KABP022) and CECT7485 (KABP023) and Pediococcus acidilactici CECT7483 (KABP021) has shown positive clinical outcomes in IBS. However, their exact mechanisms of action have not been elucidated. Postbiotics are probiotic‐derived metabolites or cell components that can improve host health. In this work we sought to characterize said strains about the production of specific postbiotics known to influence gut permeability and inflammation, as well as their inhibitory activity against bacteria known to be increased in IBS. Methods We measured the capacity to biosynthesize acetate from 3 carbon sources (glucose, xylose and arabinose) by colorimetric assay, acetylcholine (ACh) by HPLC‐ESI‐MS/MS and polyphosphate (polyP) granules by fluorescence, using Lactobacillus rhamnosus ATCC53103 as control. Inhibitory activity was tested on 6 IBS‐associated bacteria (2 enterobacteria, 2 Actinomyces spp. and 2 Streptococcus spp. strains). Supernatants from co‐cultures of probiotic and target bacteria were obtained and adjusted to pH 6 to only detect organic‐acid independent inhibition. Target bacteria were cultured on the supernatants for 16 h. Genomes were sequenced by Hiseq 2500–3000 and key genes involved in the biosynthesis of these postbiotics were searched. Additionally, susceptibility of the 3 strains to 8 antibiotics were determined according to ISO10932. Results Results are summarized in Table 1. Production of acetate was dependent on carbon source. The production from glucose was low (< 1 mM). The fermentation of xylose increased the acetate production by all the strains (3 mM approx.) while arabinose yielded the greatest concentrations (up to 13.5 mM for L. plantarum CECT7484). L. plantarum strains synthesized the largest amounts of ACh (12.5 mg/L for CECT7484 and 13.8 mg/L for CECT7485) whereas P. acidilactici CECT7483 produced 1.9 mg/L and control strain produced none. After 6 h of growth, accumulation of PolyP granules was observed for the L. plantarum and control strains but not for Pediococcus. The 3 strains produced antimicrobials against all 6 target bacteria. Consistent with phenotypic analysis, in silico study confirmed the presence of phosphofructokinase (pfk) gene (responsible for acetate synthesis) in the 3 genomes and polyphosphate kinase (ppk) gene (polyP synthesis) in the 2 L. plantarum genomes. Bacteriocin (antimicrobial compound) genes were found in the genomes of L. plantarum CECT7484 and CECT7485. Moreover, the 3 strains were susceptible to all the antibiotics tested. Conclusion The probiotic strains were proven to produce postbiotic molecules including acetate, polyP, ACh and antimicrobial compounds (potentially bacteriocins) against IBS‐associated microorganisms. This unique combination of postbiotics could explain the clinically beneficial effects of...

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