Perinatal probiotics: No benefit for allergic conditions—except eczema
Allergic disease is on the rise and continues to plague children with reduced quality of life, potentially life-threatening reactions, and missed activities, including school. The gut microbiome likely influences a child’s allergic propensity through its effects on T-helper cells, transforming growth factor (TGF), and immunoglobulin A (IgA)—all known components of the allergic response. As the hygiene hypothesis suggests, the quantity and types of bacteria that inhabit the GI tract early in life play a significant role in determining a person’s later allergic responses.13
In a 2013 meta-analysis of 20 trials (N=4866), researchers looked specifically at probiotic use and the diagnosis of asthma and incident wheezing. Single and combination products of Lactobacillus and Bifidobacterium given prenatally and/or postnatally were included in the studies. The authors found no evidence to support a protective association between perinatal use of probiotics and diagnosed asthma (RR=0.99; 95% CI, 0.81-0.21) or childhood incident wheezing (RR=0.97; 95% CI, 0.87-1.09; 9 trials, 1949 infants).14
In a more recent meta-analysis (2015) conducted to inform the World Allergy Organization, 29 studies were evaluated to assess the impact of probiotics on allergic symptoms of the skin, respiratory system, and GI tract.15 No significant benefit was noted for any allergic condition except for eczema. Probiotics reduced the risk of eczema when given during the last trimester of pregnancy (RR=0.71; 95% CI, 0.60-0.84), when used by breastfeeding mothers (RR=0.57; 95% CI, 0.47-0.69), and when given to infants (RR=0.80; 95% CI, 0.68-0.94).
A 2014 systematic review and meta-analysis (N=2797) explored probiotic use specifically for the prevention of eczema.16 The pooled relative risk for all the studies was 0.74 (95% CI, 0.67-0.82). Evidence was strongest for probiotics containing the Lactobacillus species rhamnosus and paracasei, as well as for Bifidobacterium lactis. No benefit was noted with Lactobacillus acidophilus or other Bifidobacterium species. These newer reviews on eczema prevention contrast with an older Cochrane review published in 2008 (12 RCTs, N=781), which did not show significant benefit for the treatment of eczema.17
Probiotics improve IBS stomach pain, but not diarrhea or constipation
IBS is a functional disorder of the GI tract that affects up to 20% of children and teenagers and leads to a significant decrease in quality of life.18 Current theories of causation include bacterial overgrowth and neuronal hyperactivity, which may be amenable to change with supplemental probiotics.
A 2015 systematic review of non-pharmacological treatments for functional abdominal pain disorders identified 4 studies dedicated to IBS in children.19 A subgroup analysis of 3 RCTs (n=309) that looked at giving L rhamnosus to 5- to 17-year-olds with IBS showed improved abdominal pain (according to various pain scales) compared to the placebo group. Study participants received at least 3 x 109 CFU twice a day for 4 to 8 weeks. Relative risk for improvement was 1.7 (95% CI, 1.27-2.27) with an NNT of 4. None of these studies showed significant improvement in either frequency or severity of diarrhea or constipation.
A separate crossover RCT (N=59) compared placebo to VSL#3, a product containing 8 probiotics (Bifidobacterium breve, Bifidobacterium longum, Bifidobacterium infantis, L acidophilus, Lactobacillus plantarum, L paracasei, Lactobacillus bulgaricus, and Streptococcus hermophiles), given in age-dependent doses for 6 weeks to children aged 4 to 18 years.20 The frequency and intensity of abdominal pain were measured on a 5-point Likert scale. The group treated with VSL#3 dropped 1.0 ± 0.2 points vs 0.5 ± 0.2 points in the control group (P<.05) and reported an improved quality of life.
These agents reduce antibiotic-associated diarrhea
Antibiotic-associated diarrhea (AAD) occurs in 5% to 30% of children who receive antibiotic therapy.21 It occurs most frequently with the use of cephalosporins, penicillin, fluoroquinolones, and clindamycin, and is likely caused by an alteration of the normal gut flora. Colitis caused by Clostridium difficile remains the most serious antibiotic-associated GI complication.
A systematic review of the specific probiotic Saccharomyces boulardii conducted in 2015 analyzed data from 6 RCTs (n=1653) to determine the effect of co-administration of this probiotic with antibiotics.22 The pooled relative risk for AAD in children receiving the probiotic was 0.43 (95% CI, 0.3-0.6) compared to antibiotics alone. The absolute risk of AAD dropped from 20.9% to 8.8%, translating to a NNT of 8. Two of the RCTs specifically looked at rates of C difficile infection (n=579). C difficile infection rates dropped by 75% (RR=.25; 95% CI, 0.08-0.73) in the treatment group. This dramatic treatment effect was not seen in studies involving adults.
A similar systematic review focusing on L rhamnosus conducted in 2015 pooled data from 5 RCTs (n=445) to see if the probiotic would decrease AAD in children if it was co-administered with antibiotics.23 The relative risk for AAD in this treatment group was 0.48 (95% CI, 0.26-0.89) with an absolute risk reduction of 13.4% (23% compared to 9.6%), translating to an NNT of 7.
A Cochrane review published in 2015 included 23 studies (N=3938) and found similar results with an RR for AAD of 0.46 for treated children (95% CI, 0.35-0.61).24 Doses of probiotics ranged from 5 to 40 billion CFU/day. Although many probiotic species were used in these studies, S boulardii and L rhamnosus were cited as having the strongest data to support use in this context.