Table 1.

Studies on human patients with celiac disease (CD) regarding the efficacy of probiotic supplementation.

Study	Author and Reference	Methods	Type of Probiotics	Results
Exploratory, randomized, double-blind, placebo-controlled, study on the effects of Bifidobacterium infantis Natren life start strain super strain in active celiac disease	Smecuol et al. (78)	22 patients with CD were given either probiotics or placebo for 3 weeks while not following a strict GFD.	Bifidobacterium infantis NLS super strain	The abnormal baseline intestinal permeability was not significantly affected by the treatment. Symptoms measured by the GSRS questionnaire were significantly improved in the group receiving probiotics (P = 0.0035 for indigestion; P = 0.0483 for constipation).
Administration of Bifidobacterium breve decreases the production of TNF-alpha in children with celiac disease	Klemenak et al. (79)	46 children with CD on a GFD randomized into two groups, one receiving probiotics and one receiving placebo for 3 months.	Bifidobacterium breve BR03 and B. breve B632	TNF-alpha levels significantly decreased from baseline in the probiotics group at the end of the 3 months (p = 0.020). On follow-up, 3 months after receiving probiotics, TNF-α levels increased again.
Probiotics and the microbiome in celiac disease: a randomized controlled trial	Harnett et al. (80)	A multi-center RCT conducted in Australia in 2011 on a group of 45 people with only partial response to GFD. Participants took 5 drops of VSL# twice daily for 12 weeks vs. controls taking 5 placebo drops.	VSL#3	No statistically significant changes in the fecal microbiota nor clinically significant improvement in symptoms was observed between the 2 groups.
Effect of Bifidobacterium breve on the intestinal microbiota of coeliac children on a gluten-free diet: A pilot study	Quagliarello et al. (81)	40 children with CD on a GFD were administered either two B. breve strains or placebo for 3 months. Microbial DNA was extracted from feces before and after treatment.	Bifidobacterium breve B632 and BR03 strains	A significant increase in Actinobacteria was found as well as a re-establishment of the physiological Firmicutes/Bacteroidetes ratio (p <0.01).
Celiac disease by the age of 13 years is not associated with probiotics administration in infancy	Savilahti et al. (82)	Data were taken from a trial on primary allergy prevention including 1223 babies with a high risk for allergy. Probiotics vs. placebo were given to mothers for 4 weeks before delivery and to infants until the age of 6 months.	Lactobacillus rhamnosus GG, L. rhamnosus LC 705, Bifidobacterium breve Bb99, Propionibacterium freudenreichi spp.	Probiotics administration did not affect the risk of developing CD during the 13-year follow-up.
Early probiotics supplementation and the risk of celiac disease in children at genetic risk	Uusitalo et al. (83)	Multi-center study following 6520 genetically susceptible children for a median period of 8.7 years, recording probiotics use by 1 year of age.	Various, mainly Lactobacillus reuteri and L. rhamnosus	Exposure to probiotics was not associated with a different risk of developing either celiac disease autoimmunity or celiac disease.
Clinical intervention using Bifidobacterium strains in celiac disease children reveals novel microbial modulators of TNF-α and short-chain fatty acids	Primec et al. (84)	Double-blind, placebo-controlled study of 40 children with CD who received either probiotics or placebo for 3 months.	B. breve BR03 (DSM 16604) and B. breve B632 (DSM 24706)	The Firmicutes/Bacteroides ratio was re-established. Verrucomicrobia, Parcubacteria and some yet unknown phyla, which may be involved in the disease, were highlighted, as indicated by a strong correlation to TNF-α. Modulating the production of short-chain fatty acids could play a role in restoring the microbiome.
Effects of L. plantarum and L. paracasei on the peripheral immune response in children with CD autoimmunity: a RCT	Hakansson et al. (85)	78 children with celiac disease autoimmunity received either probiotics or placebo for 6 months. Phenotyping of peripheral blood lymphocytes was conducted, and tTG was measured before and after treatment.	L. plantarum HEAL9 and L. paracasei 8700:2	Different subtypes of peripheral lymphocytes were found in the probiotics groups vs. placebo group. The median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group.