Conclusion : Limited low- quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA .
CMPA is associated with significant socioeconomic burden.• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.What is New:• This first systematic review of r and omized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP  in children at 36 months of age .
However , the evidence is low quality and influenced by data from one large study .• Probiotic supplementation was not associated with earlier resolution of hematochezia
Cow ’s milk protein allergy ( CMPA ) is the commonest food allergy in infancy and is associated with significant health burden .
Given their immune modulatory properties , probiotics have been proposed as a strategy for management of CMPA .
We aim ed to systematic ally review efficacy and safety of probiotics in the management of CMPA .
Large well- design ed trials are essential to confirm these findings .What is Known:• Cow ’s milk protein allergy ( CMPA ) is one of the commonest food allergies in children .
Markers of gut mucosal inflammation and cow’s milk specific immunoglobulins in non-IgE cow’s milk allergy
Background Allergy to cow ’s milk protein ( CMP ) may cause gastrointestinal ( GI ) symptoms in the absence of CMP specific IgE. The immunological mechanisms involved in such disease are not fully understood . Therefore we examined markers of gut mucosal inflammation and the immunoglobulin profiles in children with Gl symptoms suspected of cow ’s milk protein allergy ( CMPA ) . Patients and methods We prospect ively recruited infants and young children ( n = 57 ; median age 8.7 months ) with gastrointestinal complaints suspected of CMPA . The diagnosis of CMPA was made using the double-blind , placebo-controlled food challenge . Serum and stool sample s were collected during CMP-free diet and after both placebo and active challenges . We analyzed the stool sample s for calprotectin , human β-defensin 2 and IgA. In serum , we analyzed the levels of β-lactoglobulin and α-casein specific IgA , and IgG antibodies ( total IgG and subclasses IgG1 and IgG4 ) . Control group included children with e.g. dermatological or pulmonary problems , consuming normal diets .  Results Fecal calprotectin levels were higher in the challenge positive group ( n = 18 ) than in the negative ( n = 37 ) , with respective geometric means 55 μg/g [ 95 % confidence interval 38–81 ] and 29 [ 24–36 ] μg/g ( p = 0.0039 ) , during cow ’s milk free diet . There were no significant inter-group differences in the fecal β-defensin and IgA levels . The CMP specific IgG and IgA were not elevated in patients with CMPA , but the levels of β-lactoglobulin-IgG4 ( p = 0.0118 ) and α-casein-IgG4 ( p = 0.0044 ) , and total α-casein-IgG ( p = 0.0054 ) and -IgA ( p = 0.0050 ) in all patient sample s ( regardless of CMPA diagnosis ) were significantly lower compared to the control group using dairy products . Conclusions Despite cow ’s milk elimination in children intolerant to cow ’s milk there might be ongoing low- grade inflammation in the gut mucosa . CMP specific IgG or IgA should not be used to diagnose non-IgE CMPA . The observed frequency of impaired CMP specific total IgA , IgG and IgG4 production in patients following cow ’s milk free diet warrants further studies
Conclusion : Limited low- quality evidence indicates that probiotic supplementation may be associated with earlier acquisition of tolerance to CMP in children with CMPA .
CMPA is associated with significant socioeconomic burden.• Elimination diet and extensively hydrolyzed formula is the mainstay of the management of CMPA.What is New:• This first systematic review of r and omized controlled trials shows that probiotics as an adjuvant can lead to earlier acquisition of tolerance to CMP  in children at 36 months of age .
However , the evidence is low quality and influenced by data from one large study .• Probiotic supplementation was not associated with earlier resolution of hematochezia
Cow ’s milk protein allergy ( CMPA ) is the commonest food allergy in infancy and is associated with significant health burden .
Given their immune modulatory properties , probiotics have been proposed as a strategy for management of CMPA .
We aim ed to systematic ally review efficacy and safety of probiotics in the management of CMPA .
Large well- design ed trials are essential to confirm these findings .What is Known:• Cow ’s milk protein allergy ( CMPA ) is one of the commonest food allergies in children .