功能性胃肠病(FGID)是生命第一年的常见问题。根据罗马IV标准被认为是肠-脑轴疾病,FGIDs病因与改变的肠-脑相互作用有关,肠道生理学,和微生物群。在这方面,益生菌已成为婴儿FGID的一种有希望的疗法。在这项研究中,我们研究了从健康儿童粪便中分离的长双歧杆菌KABP042和戊糖片球菌KABP041菌株在治疗FGIDs中的益生菌潜力。在这个范围内,获得了两个菌株的基因组序列,并进行了计算机模拟分析。没有检测到任何菌株的毒力因子,只有不可转移的erm(49)基因,赋予对红霉素和克林霉素的耐药性,在长双歧杆菌KABP042的基因组中鉴定。两种菌株的安全性均通过大鼠急性口服毒性得到证实。体外鉴定表明,该菌株能耐受胃和胆汁的挑战,并对人肠细胞具有很强的粘附能力。两种菌株通过不同的机制介导粘附,当合并时,协同诱导Caco-2紧密连接蛋白的表达。此外,生长抑制实验证明了两种菌株单独和组合在固着和浮游生长过程中拮抗多种革兰氏阴性和革兰氏阳性细菌病原体的能力。病原体抑制主要由有机酸的产生介导,但中和实验强烈表明,在益生菌培养上清液中存在额外的抗微生物化合物,如细菌素LanticB,在长双歧杆菌KABP042的基因组中检测到其基因。最后,一个探索者,观察,纳入36例被诊断患有至少一种FGID(婴儿绞痛和/或功能性便秘)的婴儿的初步研究表明,在使用2种菌株治疗14天后,益生菌配方具有良好的耐受性,FGID严重程度显著降低.总的来说,这项工作提供了长芽孢杆菌KABP042和戊糖芽孢杆菌KABP041菌株的益生菌和协同特性的证据,以及它们治疗小儿FGID的潜力.临床试验注册:[www.ClinicalTrials.gov],[标识符NCT04944628]。
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].