The Effects of Microbiome Modulating Therapies on Inflammatory Markers in Autoimmune Disease: A Systematic Review and...

Autoimmune diseases (ADs) are a growing global health burden, driven by chronic inflammation and immune dysregulation. The gut-immune axis plays a central role in their pathogenesis, with dysbiosis linked to several conditions. This has prompted investigation into nutraceuticals such as probiotics, prebiotics, synbiotics, and fecal microbiota transplantation as adjunctive therapies.

We conducted a systematic review and meta-analysis following PRISMA guidelines, searching PubMed, Embase, and Web of Science for randomized controlled trials evaluating these interventions in autoimmune diseases.

Twenty-eight randomized control trials (RCTs) involving 2002 patients across 11 countries met inclusion criteria. Across the included RCTs, pooled analyses demonstrated significant reductions in c-reactive protein (CRP) (SMD -0.67, 95% CI -1.00 to -0.33; I² = 80.8%) and Tumor necrosis factor-alpha (TNF-α) (SMD -1.81, 95% CI -2.67 to -0.94; I² = 96%), a significant increase in Interleukin-10 (IL-10) (SMD 2.65, 95% CI 0.64 to 4.66; I² = 98%), and no overall significant effect on Interleukin-6 (IL-6) (SMD -0.89, 95% CI -1.99 to 0.22; p = 0.12). The strongest evidence of benefit was observed in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease. Pooled effects are limited by extreme between-study heterogeneity (I² 80-98%), leaving interpretation as exploratory rather than definitive. More limited or inconsistent findings were reported for systemic lupus erythematosus, hypothyroidism, axial spondylarthritis, and juvenile idiopathic arthritis. Heterogeneity in study design, probiotic strain selection, dosage, and treatment duration limited comparability across trials.

Overall, microbiome-targeted nutraceuticals appear promising for attenuating systemic inflammation in select autoimmune conditions, but results remain mixed. Larger, rigorously designed RCTs with standardized endpoints are needed to clarify efficacy, identify optimal formulations, and define patient populations most likely to benefit.