Effects of Lactobacillus plantarum and Lactobacillus paracasei on the Peripheral Immune Response in Children with Celiac Disease Autoimmunity: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Åsa Håkansson,Carin Andrén Aronsson,Charlotte Brundin,Elin Oscarsson,Göran Molin,Daniel Agardh

doi:10.3390/nu11081925

Abstract

Two Lactobacillus strains have proven anti-inflammatory properties by reducing pro-inflammatory responses to antigens. This randomized double-blind placebo-controlled trial tested the hypothesis that L. plantarum HEAL9 and L. paracasei 8700:2 suppress ongoing celiac disease autoimmunity in genetically at risk children on a gluten-containing diet in a longitudinally screening study for celiac disease. Seventy-eight children with celiac disease autoimmunity participated of whom 40 received 1010 CFU/day of L. plantarum HEAL9 and L. paracasei 8700:2 (probiotic group) and 38 children maltodextrin (placebo group) for six months. Blood samples were drawn at zero, three and six months and phenotyping of peripheral blood lymphocytes and IgA and IgG autoantibodies against tissue transglutaminase (tTG) were measured. In the placebo group, naïve CD45RA+ Th cells decreased (p = 0.002) whereas effector and memory CD45RO+ Th cells increased (p = 0.003). In contrast, populations of cells expressing CD4+CD25highCD45RO+CCR4+ increased in the placebo group (p = 0.001). Changes between the groups were observed for NK cells (p = 0.038) and NKT cells (p = 0.008). Median levels of IgA-tTG decreased more significantly over time in the probiotic (p = 0.013) than in the placebo (p = 0.043) group whereas the opposite was true for IgG-tTG (p = 0.062 respective p = 0.008). In conclusion, daily oral administration of L. plantarum HEAL9 and L. paracasei 8700:2 modulate the peripheral immune response in children with celiac disease autoimmunity.

Highlights

Changes in the intestinal microbiota and dysregulation of the mucosal immune response may contribute to the pathogenesis of different inflammatory and autoimmune disorders
The present combination of two Lactobacillus strains are chosen due to their different physiological effects, i.e., L. plantarum HEAL9 is targeting the permeability of the mucosa and L. paracasei 8700:2 is targeting the immune system [12,13,14,15]
As of 1 February 2019, biopsy-proven celiac disease was diagnosed in six children (15%) in the probiotic group and five children (13%) in the placebo group after the study ended (p = 0.818)

Summary

Introduction

Changes in the intestinal microbiota and dysregulation of the mucosal immune response may contribute to the pathogenesis of different inflammatory and autoimmune disorders. Probiotics, defined as live microorganisms which when administrated in adequate amounts confer a health benefit [1], are known to have immunomodulatory influences on leucocyte populations and lymphocyte phenotypes [2], the ability to promote the endogenous defense barrier in the human gut [3], and the ability to decrease mucosal permeability [4]. Subsequent studies have shown that probiotics can reduce autoimmune responses in patients with rheumatoid arthritis by improving inflammatory status and disease activity [6]. Further studies are required to evaluate reproducibility and health promoting effects of probiotics in autoimmune diseases, several larger meta-analyses have shown improvements of clinical conditions [9,10,11]. The present combination of two Lactobacillus strains are chosen due to their different physiological effects, i.e., L. plantarum HEAL9 is targeting the permeability of the mucosa and L. paracasei 8700:2 is targeting the immune system [12,13,14,15]

Methods

Results

Discussion

Conclusion