Judith R Lowe1, Andrew M Briggs2, Sam Whittle3, Matthew D Stephenson4. 1. Joanna Briggs Institute, University of Adelaide, South Australia, Australia. Electronic address: Jlowe@unley.sa.gov.au. 2. School of Physiotherapy and Exercise Science, Curtin University, Western Australia, Australia. Electronic address: A.Briggs@curtin.edu.au. 3. Department of Rheumatology, The Queen Elizabeth Hospital, Adelaide, South Australia, Australia. Electronic address: Samuel.Whittle@sa.gov.au. 4. Joanna Briggs Institute, University of Adelaide, South Australia, Australia. Electronic address: matthew.stephenson@adelaide.edu.au.
Abstract
OBJECTIVE: To systematically identify and appraise evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis. METHODS: MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics in populations with inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools. RESULTS: The search identified 5876 unique articles, with 154 potentially relevant full text articles retrieved. Twelve studies met the inclusion criteria and were included in the review, of which ten (83%) were randomised control trials (RCT) and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpAs) and eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median of 60 days and mode of 56 days across all included studies (range 7-365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24 hrs ranging from 1 × 108 to 2.25 × 1011. The order of probiotics supplied to the most participants and across the most studies was Lactobacillales. There was no statistical difference in the relative risk (RR) of minor adverse events between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) of -0.37 (95% CI -0.59,-0.15) with subgroup analysis favouring Lactobacillales-only formulations. Small but statistically significant reductions in pain were identified, with a mean difference (MD) of -8.97 (95% CI-15.38, -2.56) on a 100mm visual analogue scale, independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein (CRP) concentration MD (mg/L) -2.33 (95% CI -4.26, -0.41), with subgroup analysis demonstrating a greater effect in RA and from combined Bifidobacteriales and Lactobacillales formulations. CONCLUSION: This review indicates there may be differential benefits to combined formulations of Bifidobacteriales and Lactobacillales compared to purely Lactobacillales formulations, with respect to reducing pain, lowering CRP and improving quality of life. It also suggests variable benefits associated with the type of inflammatory arthritis. Relatively less benefit for lowering CRP was attributed to individuals with SpA compared to individuals with RA. Generalisability of results to clinical practice is limited by the dominant demographic of older individuals with established disease beyond the 'therapeutic window of intervention'. Small but statistically significant benefits require confirmation in clinical studies with greater consideration to potentially confounding factors of age, gender, diet and individual microbial signature.
OBJECTIVE: To systematically identify and appraise evidence of the formulation specific effects and population specific responses of probiotics in inflammatory arthritis. METHODS: MEDLINE (PubMed), CINAHL, EMBASE, and SCOPUS databases were searched for studies utilising probiotics in populations with inflammatory arthritis. The Joanna Briggs Institute (JBI) method was used to conduct the systematic review. A single reviewer undertook screening and data extraction. Two independent reviewers assessed the quality of evidence using JBI tools. RESULTS: The search identified 5876 unique articles, with 154 potentially relevant full text articles retrieved. Twelve studies met the inclusion criteria and were included in the review, of which ten (83%) were randomised control trials (RCT) and two (17%) were quasi-experimental studies. Four studies included a variety of spondyloarthopathies (SpAs) and eight studies focused on rheumatoid arthritis (RA). Probiotics were supplied for a median of 60 days and mode of 56 days across all included studies (range 7-365 days). Overall, 17 different probiotics were supplied in colony forming units (CFU) per 24 hrs ranging from 1 × 108 to 2.25 × 1011. The order of probiotics supplied to the most participants and across the most studies was Lactobacillales. There was no statistical difference in the relative risk (RR) of minor adverse events between probiotic and control groups (RR 1.02, 95% CI 0.69 to 1.51) when including nil event studies. Meta-analysis identified a statistically significant benefit of probiotics on quality of life with a standard mean difference (SMD) of -0.37 (95% CI -0.59,-0.15) with subgroup analysis favouring Lactobacillales-only formulations. Small but statistically significant reductions in pain were identified, with a mean difference (MD) of -8.97 (95% CI-15.38, -2.56) on a 100mm visual analogue scale, independent of formulation. Meta-analysis confirmed the known statistically significant benefit of probiotics on the inflammatory marker C-reactive protein (CRP) concentration MD (mg/L) -2.33 (95% CI -4.26, -0.41), with subgroup analysis demonstrating a greater effect in RA and from combined Bifidobacteriales and Lactobacillales formulations. CONCLUSION: This review indicates there may be differential benefits to combined formulations of Bifidobacteriales and Lactobacillales compared to purely Lactobacillales formulations, with respect to reducing pain, lowering CRP and improving quality of life. It also suggests variable benefits associated with the type of inflammatory arthritis. Relatively less benefit for lowering CRP was attributed to individuals with SpA compared to individuals with RA. Generalisability of results to clinical practice is limited by the dominant demographic of older individuals with established disease beyond the 'therapeutic window of intervention'. Small but statistically significant benefits require confirmation in clinical studies with greater consideration to potentially confounding factors of age, gender, diet and individual microbial signature.