Fatheree Nicole Y, Liu Yuying, Ferris Michael, Van Arsdall Melissa, McMurtry Valarie, Zozaya Marcela, Cai Chunyan, Rahbar Mohammad H, Hessabi Manouchehr, Vu Ta, Wong Christine, Min Juleen, Tran Dat Q, Navarro Fernando, Gleason Wallace, Gonzalez Sara, Rhoads J Marc
Nicole Y Fatheree, Yuying Liu, Melissa Van Arsdall, Juleen Min, Dat Q Tran, Fernando Navarro, Wallace Gleason, Sara Gonzalez, J Marc Rhoads, Department of Pediatrics, the University of Texas Health Science Center at Houston Medical School, Houston, TX 77030, United States.
World J Gastrointest Pathophysiol. 2016 Feb 15;7(1):160-70. doi: 10.4291/wjgp.v7.i1.160.
To investigate recruitment, retention, and estimates for effects of formula supplementation with Lactobacillus rhamnosus GG (LGG) on inflammatory biomarkers and fecal microbial community in infants with colic.
A prospective, double-blind, placebo-controlled trial was conducted in otherwise healthy infants with colic. We screened 74 infants and randomized and analyzed results in 20 infants [9 receiving LGG (LGG+) and 11 not receiving LGG (LGG-)]. LGG was incorporated in the formula (Nutramigen(®)) (minimum of 3 × 10(7) CFU/d) in the LGG+ group. Fecal microbiota and inflammatory biomarkers, including fecal calprotectin (FC), plasma cytokines, circulating regulatory T cells (Tregs), and crying + fussing time were analyzed to determine optimal time points and effect sizes for a larger trial.
Recruitment in this population was slow, with about 66% of eligible infants willing to enroll; subject retention was better (75%). These rates were influenced by parents' reluctance to volunteer their infant for a clinical trial and by their tendency to change formulas. The maximal difference of crying + fussing time was observed at day 14, comparing the 2 groups, with a mean difference of -91 (95%CI: -76, 259) min (P = NS). FC showed no significant difference, but the optimal time to determine a potential effect was at day 90 [with a mean difference of 121 (95%CI: -48, 291) μg/g stool], observing a lower level of FC in the LGG+ group. The fecal microbial communities were chaotic, as determined by Shannon's diversity index and not apparently influenced by the probiotic. No significant change was observed in plasma inflammatory cytokines or Tregs, comparing LGG+ to LGG- groups.
Designing future colic trials involving a probiotic-supplemented formula for infants in the United States will require consideration for difficult enrollment. Infants with colic have major variations in feal microbiota and calprotectin, both of which improve with time, with optimal time points for measurement at days 14 and 90 after treatment.
研究补充鼠李糖乳杆菌GG（LGG）配方奶对患有腹绞痛婴儿的炎症生物标志物和粪便微生物群落的招募、留存情况及效果评估。
对其他方面健康的腹绞痛婴儿进行一项前瞻性、双盲、安慰剂对照试验。我们筛查了74名婴儿，对其中20名进行随机分组并分析结果[9名接受LGG（LGG+组），11名未接受LGG（LGG-组）]。LGG+组的配方奶（纽迪希亚（Nutramigen(®)））中添加了LGG（最低3×10⁷CFU/天）。分析粪便微生物群和炎症生物标志物，包括粪便钙卫蛋白（FC）、血浆细胞因子、循环调节性T细胞（Tregs）以及哭闹+烦躁时间，以确定更大规模试验的最佳时间点和效应大小。
该人群的招募速度较慢，约66%符合条件的婴儿愿意入组；受试者留存情况较好（75%）。这些比率受到父母不愿让婴儿参加临床试验以及他们更换配方奶倾向的影响。比较两组，在第14天观察到哭闹+烦躁时间的最大差异，平均差异为-91（95%CI：-76，259）分钟（P =无统计学意义）。FC无显著差异，但确定潜在效应的最佳时间是第90天[平均差异为121（95%CI：-48，291）μg/g粪便]，观察到LGG+组的FC水平较低。根据香农多样性指数确定，粪便微生物群落混乱，且未明显受到益生菌的影响。比较LGG+组和LGG-组，血浆炎症细胞因子或Tregs未观察到显著变化。
在美国设计未来涉及为婴儿补充益生菌配方奶的腹绞痛试验时，需要考虑招募困难的问题。患有腹绞痛的婴儿粪便微生物群和钙卫蛋白有很大差异，两者均随时间改善，治疗后第14天和第90天是测量的最佳时间点。
