Published online Feb 15, 2016. doi: 10.4291/wjgp.v7.i1.160
Peer-review started: March 31, 2015
First decision: June 18, 2015
Revised: September 25, 2015
Accepted: November 3, 2015
Article in press: November 4, 2015
Published online: February 15, 2016
AIM: 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.
METHODS: 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 × 107 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.
RESULTS: 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.
CONCLUSION: 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.
Core tip: The “dysbiosis” theory proposes that newborns with abnormal colonization are predisposed to having gut inflammation and colic. Probiotics may reduce crying and diversify the fecal microbiota. A prospective, double-blind, placebo-controlled trial was conducted in healthy infants with colic. After 75% screen failure or dropouts, 20 infants were analyzed (9 receiving formula with Lactobacillus GG and 11 not receiving Lactobacillus rhamnosus GG in their formula). We found that: (1) recruitment/retention indicate future randomized controlled trials should enroll 80 patients with an optimal timepoint for observing a potential difference in crying at 14 d; (2) microbial communities were chaotic in infants with colic, even more so than reported in Dutch infants; and (3) our study was the first to analyze cytokine levels and circulating Tregs in infants with colic.