Effect of probiotics on clinical and immune parameters in enthesitis-related arthritis category of juvenile idiopathic arthritis

Abstract

Gut microflora and dysbiosis as an environmental factor has been linked to the pathogenesis of enthesitis-related arthritis (JIA-ERA); thus, we performed a proof-of-concept study of probiotics to modulate the gut-flora and study the effects on immune and clinical parameters of children having JIA-ERA. Forty-six children with active JIA-ERA were randomized to placebo or probiotic therapy along with non-steroidal anti-inflammatory drugs (NSAIDs) for 12 weeks. Patients were assessed using a six-point composite disease activity index (mJSpADA) based on morning stiffness, joint count, enthesitis count, sacroiliitis/inflammatory back pain, uveitis and erythrocyte sedimentation rate/C-reactive protein (ESR/CRP). Frequencies of T helper type 1 (Th1), Th2, Th17 and regulatory T cells in blood were measured using flow cytometry. Serum cytokines interferon (IFN)-γ, interleukin (IL)-4, IL-17, IL-10, tumour necrosis factor (TNF)-α and IL-6 were measured by cytokine bead array using flow cytometer. The average age of 46 children (44 boys) was 15 ± 2.5 years and duration of disease was 3.5 ± 3 years. There was no significant difference in improvement in mJSpADA between the two groups (P = 0·16). Serum IL-6 levels showed a decrease (P < 0·05) in the probiotic-group. Th2 cell frequency (P < 0·05) and serum IL-10 levels (P < 0·01) showed an increase in the placebo group, but again the probiotic use did not show a significant change in immune parameters when compared to the placebo. Adverse effects among the probiotic and placebo groups were diarrhea (36 versus 45%), abdominal pain (9 versus 20%), minor infections (4·5 versus 20%) and flatulence (23 versus 15%), respectively. Thus, we can conclude that probiotic therapy in JIA-ERA children is well tolerated, but failed to show any significant immune or clinical effects over NSAID therapy.

Microbial orchestra in juvenile idiopathic arthritis: Sounds of disarray?

“…The selection of probiotics may need to be based not on what works in IBD, but rather on the demonstrated deficiencies in the target population, for example, children with JIA. This was not the case in the Aggarwal study, in which several of the bacteria that constitute VSL # 3 were normal if not elevated in the ERA population compared to the controls (Table ) …”

“…To date, there has been only one study of probiotics in children with JIA . In this study, patients with long‐standing ERA with average disease duration of 3 years were randomized to twice daily administration of placebo or the VSL 3 probiotic, which contains Streptococcus thermophilus, Bifidobacterium breve, B longum, B infantis, Lactobacillus acidophilus, L plantarum, L paracasei, and L delbrueckii; both groups were also treated with non‐steroidal anti‐inflammatory drugs for the duration of the 12‐week study, but no patients were on immunosuppressive therapy.…”

“…While these studies may suggest therapeutic potential of Lactobacillus ‐containing probiotics, enthusiasm is dampened by the failure of the VSL # 3 trial in children with ERA, as this probiotic includes Lactobacillus . The issue may represent failure of the probiotic to adhere to the host mucosa.…”

“…126 To date, there has been only one study of probiotics in children with JIA. 127 In this study, patients with long-standing ERA with average disease duration of 3 years were randomized to twice daily administration of placebo or the VSL 3 probiotic, which con- These negative findings corroborate two prior studies that likewise yielded negative findings in adult patients with SpA. One was a 12-week randomized trial of a mixture of three strains Streptococcus salivarius, Bifidobacterium lactis, and Lactobacillus acidophilus administered for 12 weeks, which demonstrated no differences in an array of clinical parameters between the placebo and intervention arms.…”

“…[130][131][132] Does this necessarily mean that probiotics do not have a place in the management of JIA in general, or even of arthritis more broadly This was not the case in the Aggarwal study, in which several of the bacteria that constitute VSL # 3 were normal if not elevated in the ERA population compared to the controls (Table 3). 7,127 Given the findings of decreased F prausnitzii in children with ERA, 8 Enterococcus faecium) can increase endogenous SCFA production, primarily by increased production of lactate, which is a substrate used for SCFA production. 133 Additionally, L acidophilus can upregulate colonic expression of the monocarboxylate transporter I, which is required for transport of butyrate into colonic cells.…”