Probiotic Properties of Bifidobacterium longum KABP042 and Pediococcus pentosaceus KABP041 Show Potential to Counteract Functional Gastrointestinal Disorders in an Observational Pilot Trial in Infants

Abstract

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].

Study of the biosynthesis and functionality of polyphosphate in Bifidobacterium longum KABP042

“…longum is a typical inhabitant of the intestinal tract of breast-fed infants. Speci cally, the strain KABP042 originated from feces of a breastfed infant and is known to exert bene cial effects in lactating infants with colic 19 . Because B. longum and human milk interact in the infant gut we tested the effect of breast milk (which is known to contain around 4.5 mM Pi 20 ) and speci c milk components on poly-P synthesis in the KAPB042 strain.…”

“…In addition, we used the poly-P-producer probiotic strain B. longum KABP042 to investigate the effect of environmental Pi and whether poly-P formation is involved in protection against acidic or oxidative challenges. Since KABP042 was isolated from the faeces of a breastfed infant 19 and breast milk contains Pi 20 , the effect of breast milk and milk bioactive compounds including human milk oligosaccharides (HMO) and polyamines on poly-P synthesis was also investigated. Furthermore, the effect of B. longum KABP042-derived poly-P in the human intestinal barrier was assessed in vitro by measuring barrier permeability and resistance and the induction of protective factors involved in barrier integrity.…”

In vitro intestinal simulation system on the carbon source utilization characteristics and mechanism of interspecific syntrophic effects of Bifidobacterium longum CECT7894 and Pediococcus pentosaceus CECT8330

“…Although the combination of B. longum and P. pentosaceus has been clinically proven to be effective in the treatment of infantile colic, few studies have investigated the corresponding mechanisms of action in the intestine. Astó et al ( 9 ) conducted in vitro experiments on the potential mechanism of B. longum and P. pentosaceus in the treatment of infantile colic, finding that both strains could tolerate gastric acid, bile salt, as well as other environmental conditions, and could effectively adhere to human intestinal epithelial cells, while synergistically regulating the expression of tight junction-related genes. Notably, these characteristics are crucial for maintaining the integrity of the intestinal barrier.…”

“…Furthermore, as the probiotic use continued, time and frequency of crying continued to decrease, in addition to significant improvements in the stool properties of infants. Erola et al ( 9 ) similarly demonstrated in their research that the two-strain probiotic combination had a synergistic effect in increasing the diversity of intestinal adhesion proteins during the treatment of infantile colic, in addition to validating its safety and efficacy.…”

The Probiotic Properties and Safety of Limosilactobacillus mucosae NK41 and Bifidobacterium longum NK46

“…In previous studies, some strains of L. mucosae were found to be resistant to tetracycline, gentamicin, vancomycin, streptomycin, clindamycin, and erythromycin [11,23,29]. B. longum KABP042, isolated from the feces of healthy children, showed resistance to erythromycin and clindamycin [46]. Furthermore, Shin et al [47] reported that many commercial probiotic strains exhibit resistance to various clinically relevant antibiotics.…”