Impact of bacterial probiotics on obesity, diabetes and non-alcoholic fatty liver disease related variables: a systematic review and meta-analysis of randomised controlled trials

Abstract

Objective: To systematically review the effect of oral intake of bacterial probiotics on 15 variables related to obesity, diabetes and non-alcoholic fatty liver disease.

Design: Systematic review and meta-analysis.

Data sources: Medline, EMBASE and COCHRANE from 1990 to June 2018.

Eligibility criteria: Randomised controlled trials (≥14 days) excluding hypercholesterolaemia, alcoholic liver disease, polycystic ovary syndrome and children <3 years.

Results: One hundred and five articles met inclusion criteria, representing 6826 subjects. In overweight but not obese subjects, probiotics induced improvements in: body weight (k=25 trials, d=-0.94 kg mean difference, 95% CI -1.17 to -0.70, I²=0.0%), body mass index (k=32, d=-0.55 kg/m², 95% CI -0.86 to -0.23, I²=91.9%), waist circumference (k=13, d=-1.31 cm, 95% CI -1.79 to -0.83, I²=14.5%), body fat mass (k=11, d=-0.96 kg, 95% CI -1.21 to -0.71, I²=0.0%) and visceral adipose tissue mass (k=5, d=-6.30 cm², 95% CI -9.05 to -3.56, I²=0.0%). In type 2 diabetics, probiotics reduced fasting glucose (k=19, d=-0.66 mmol/L, 95% CI -1.00 to -0.31, I²=27.7%), glycated haemoglobin (k=13, d=-0.28 pp, 95% CI -0.46 to -0.11, I²=54.1%), insulin (k=13, d=-1.66 mU/L, 95% CI -2.70 to -0.61, I²=37.8%) and homeostatic model of insulin resistance (k=10, d=-1.05 pp, 95% CI -1.48 to -0.61, I²=18.2%). In subjects with fatty liver diseases, probiotics reduced alanine (k=12, d=-10.2 U/L, 95% CI -14.3 to -6.0, I²=93.50%) and aspartate aminotransferases (k=10, d=-9.9 U/L, 95% CI -14.1 to -5.8, I²=96.1%). These improvements were mostly observed with bifidobacteria (Bifidobacterium breve, B. longum), Streptococcus salivarius subsp. thermophilus and lactobacilli (Lactobacillus acidophilus, L. casei, L. delbrueckii) containing mixtures and influenced by trials conducted in one country.

Conclusions: The intake of probiotics resulted in minor but consistent improvements in several metabolic risk factors in subjects with metabolic diseases.

Trial registration number: CRD42016033273.

Keywords: bifidobacterium; diabetes; lactobacillus; non-alcoholic fatty liver disease; obesity; probiotics.

Figure 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses flow diagram.

Figure 2

Results of meta-analyses: overall estimates and estimates obtained in specific study populations: (A) anthropometric variables and BMI, (B) glucose homeostasis, (C) liver enzymes. (X-axis) Absolute difference in mean change from baseline (probiotics—control groups): random effects estimate and 95% CI; outcomes (measurement unit): ALAT, alanine aminotransferase; ALL, all studies pooled; ASAT, aspartate aminotransferase; BFM, body fat mass; BMI, body mass index; BW, body weight; FG, fasting glucose; GGT, gamma-glutamyl transferase; HbA_1c, glycated haemoglobin; HOMA-IR, homeostatic model assessment of insulin resistance; IFG, impaired fasting glucose; INS, fasting insulin; NAFLD, non-alcoholic fatty liver disease; NW, normal weight; OB, obese; OW, overweight, T2DM, type 2 diabetes mellitus, WC, waist circumference.

Figure 3

Results of subgroup meta-analyses stratified by probiotics species and total number of different species administered (data shown for at least three trials): (A) body weight (kg), (b) fasting glucose (mmol/L), (C) glycated haemoglobin (%). (X-axis) Absolute difference in mean change from baseline (probiotics group—control group): random effects estimate and 95% CI. B. bif, Bifidobacterium bifidum; B. brev, Bifidobacterium breve; B. lac., Bifidobacterium animalis subsp. lactis; B. lon., Bifidobacterium longum; S. therm., Streptococcus salivarius subsp. thermophilus; Lc. lact, Lactococcus lactis; L. hel., Lactobacillus helveticus; L. acid., Lactobacillus acidophilus; L. del., Lactobacillus delbrueckii; L. gas., Lactobacillus gasseri; L. reut., Lactobacillus reuteri; L. fer., Lactobacillus fermentum; L. rham., Lactobacillus rhamnosus; L. cas. gr., Lactobacillus casei or paracasei; L. sal., Lactobacillus salivarius; L. plan., Lactobacillus plantarum.