Efficacy of Lactobacillus rhamnosus GG in treatment of acute pediatric diarrhea: A systematic review with meta-analysis

Abstract

Background: Diarrhea is a major infectious cause of childhood morbidity and mortality worldwide. In clinical trials, Lactobacillus rhamnosus GG ATCC 53013 (LGG) has been used to treat diarrhea. However, recent randomized controlled trials (RCTs) found no evidence of a beneficial effect of LGG treatment.

Aim: To evaluate the efficacy of LGG in treating acute diarrhea in children.

Methods: The EMBASE, MEDLINE, PubMed, Web of Science databases, and the Cochrane Central Register of Controlled Trials were searched up to April 2019 for meta-analyses and RCTs. The Cochrane Review Manager was used to analyze the relevant data.

Results: Nineteen RCTs met the inclusion criteria and showed that compared with the control group, LGG administration notably reduced the diarrhea duration [mean difference (MD) -24.02 h, 95% confidence interval (CI) (-36.58, -11.45)]. More effective results were detected at a high dose ≥ 10¹⁰ CFU per day [MD -22.56 h, 95%CI (-36.41, -8.72)] vs a lower dose. A similar reduction was found in Asian and European patients [MD -24.42 h, 95%CI (-47.01, -1.82); MD -32.02 h, 95%CI (-49.26, -14.79), respectively]. A reduced duration of diarrhea was confirmed in LGG participants with diarrhea for less than 3 d at enrollment [MD -15.83 h, 95%CI (-20.68, -10.98)]. High-dose LGG effectively reduced the duration of rotavirus-induced diarrhea [MD -31.05 h, 95%CI (-50.31, -11.80)] and the stool number per day [MD -1.08, 95%CI (-1.87, -0.28)].

Conclusion: High-dose LGG therapy reduces the duration of diarrhea and the stool number per day. Intervention at the early stage is recommended. Future trials are expected to verify the effectiveness of LGG treatment.

Keywords: Acute diarrhea; Children; Lactobacillus rhamnosus GG; Meta-analysis; Probiotics; Rotavirus; Systematic review.

Figure 1

Lactobacillus GG vs control with regard to the duration of diarrhea (hours). A: High dose and low dose; B: The duration of diarrhea before Lactobacillus rhamnosus GG participants’ enrollment: ≤2 d (>1 d), ≤3 d (>2 d), and ≤4 d (>3 d); C: Geography of the clinical trials: Asia, Europe, and other continents. LGG: Lactobacillus rhamnosus GG; CI: Confidence interval; SD: Standard deviation.

Figure 2

Lactobacillus GG vs control with regard to mean duration of diarrhea (hours) in children with rotavirus diarrhea. LGG: Lactobacillus rhamnosus GG; CI: Confidence interval; SD: Standard deviation.

Figure 3

Lactobacillus GG vs control with regard to the presence of diarrhea. A: Diarrhea lasting > 3 d; B: Diarrhea lasting > 4 d. LGG: Lactobacillus rhamnosus GG; CI: Confidence interval.

Figure 4

Lactobacillus GG vs control with regard to stool number and consistency. A: The average stool number per day (high dose and low dose); B: Stool frequency on day 2; C: Stool frequency on day 3; D: The mean time to improvement in stool consistency. LGG: Lactobacillus rhamnosus GG; CI: Confidence interval; SD: Standard deviation.

Figure 5

Lactobacillus GG vs control. A: The duration of hospital stay (hours); B: The hospital stay duration of rotavirus-positive children (hours). LGG: Lactobacillus rhamnosus GG; CI: Confidence interval; SD: Standard deviation.

Figure 6

Lactobacillus GG vs control with regard to vomiting. A: The number of participants with vomiting [number (%)]; B: The duration of vomiting (hours). LGG: Lactobacillus rhamnosus GG; CI: Confidence interval; SD: Standard deviation.