# The Effects of Microbiome Modulating Therapies on Inflammatory Markers in Autoimmune Disease: A Systematic Review and Meta-Analysis

**Authors:** Ghalya Ashkanani, Mlaak Rob, Mahmoud Yousef, Alia Ashkanani, Yousef A. Al-Najjar, Sa’ad Laws, Ali Chaari

PMC · DOI: 10.3390/nu18040560 · 2026-02-08

## TL;DR

This study reviews how gut microbiome therapies affect inflammation in autoimmune diseases, finding some promise but highlighting the need for more consistent research.

## Contribution

The paper provides a comprehensive meta-analysis of microbiome modulating therapies in autoimmune diseases, highlighting their effects on inflammatory markers.

## Key findings

- Microbiome therapies significantly reduced CRP and TNF-α in autoimmune diseases.
- IL-10 levels increased significantly, but no significant effect was found for IL-6.
- Strongest benefits were observed in rheumatoid arthritis, multiple sclerosis, and inflammatory bowel disease.

## Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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.

## Linked entities

- **Proteins:** IL10 (interleukin 10), IL6 (interleukin 6)
- **Diseases:** rheumatoid arthritis (MONDO:0008383), multiple sclerosis (MONDO:0005301), inflammatory bowel disease (MONDO:0005265), systemic lupus erythematosus (MONDO:0007915), hypothyroidism (MONDO:0005420), juvenile idiopathic arthritis (MONDO:0011429)

## Full-text entities

- **Genes:** MYD88 (MYD88 innate immune signal transduction adaptor) [NCBI Gene 4615] {aka IMD68, MYD88D, WM1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, Stat3 (signal transducer and activator of transcription 3) [NCBI Gene 20848] {aka 1110034C02Rik, Aprf}, Foxp3 (forkhead box P3) [NCBI Gene 20371] {aka JM2, scurfin, sf}, IL12B (interleukin 12B) [NCBI Gene 3593] {aka CLMF, CLMF2, IL-12B, IMD28, IMD29, NKSF}, Cxcl15 (C-X-C motif chemokine ligand 15) [NCBI Gene 20309] {aka Il8, Scyb15, lungkine, weche}, Cldn2 (claudin 2) [NCBI Gene 12738], Il6 (interleukin 6) [NCBI Gene 16193] {aka Il-6}, Egfr (epidermal growth factor receptor) [NCBI Gene 13649] {aka 9030024J15Rik, Erbb, Errb1, Errp, Wa5, wa-2}, IL6ST (interleukin 6 cytokine family signal transducer) [NCBI Gene 3572] {aka CD130, CDW130, GP130, HIES4, HIES4A, HIES4B}, Il17a (interleukin 17A) [NCBI Gene 16171] {aka Ctla-8, Ctla8, IL-17, IL-17A, Il17}, Il1b (interleukin 1 beta) [NCBI Gene 16176] {aka IL-1beta, Il-1b}, IL10 (interleukin 10) [NCBI Gene 3586] {aka CSIF, GVHDS, IL-10, IL10A, TGIF}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}, IL23A (interleukin 23 subunit alpha) [NCBI Gene 51561] {aka IL-23, IL-23A, IL23P19, P19, SGRF}, Cat (catalase) [NCBI Gene 12359] {aka 2210418N07, Cas-1, Cas1, Cs-1}, STAT3 (signal transducer and activator of transcription 3) [NCBI Gene 6774] {aka ADMIO, ADMIO1, APRF, HIES}, Tnf (tumor necrosis factor) [NCBI Gene 21926] {aka DIF, TNF-a, TNF-alpha, TNFSF2, TNFalpha, Tnfa}, Il23a (interleukin 23, alpha subunit p19) [NCBI Gene 83430] {aka IL-23, p19}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, TLR4 (toll like receptor 4) [NCBI Gene 7099] {aka ARMD10, CD284, TLR-4, TOLL}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, IL37 (interleukin 37) [NCBI Gene 27178] {aka FIL1, FIL1(ZETA), FIL1Z, IL-1F7, IL-1H, IL-1H4}, Nfkb1 (nuclear factor of kappa light polypeptide gene enhancer in B cells 1, p105) [NCBI Gene 18033] {aka NF-KB1, NF-kappaB, NF-kappaB1, p105, p50, p50/p105}, IL17A (interleukin 17A) [NCBI Gene 3605] {aka CTLA-8, CTLA8, IL-17, IL-17A, IL17, ILA17}, Nfe2l2 (nuclear factor, erythroid derived 2, like 2) [NCBI Gene 18024] {aka Nrf2}, CD79A (CD79a molecule) [NCBI Gene 973] {aka IGA, IGAlpha, MB-1, MB1}, Crp (C-reactive protein, pentraxin-related) [NCBI Gene 12944], Il10 (interleukin 10) [NCBI Gene 16153] {aka CSIF, If2a, Il-10}, Ffar2 (free fatty acid receptor 2) [NCBI Gene 233079] {aka GPCR43, Gpr43}, HLA-C (major histocompatibility complex, class I, C) [NCBI Gene 3107] {aka D6S204, HLA-JY3, HLAC, HLC-C, MHC, PSORS1}, Tlr4 (toll-like receptor 4) [NCBI Gene 21898] {aka Lps, Ly87, Ran/M1, Rasl2-8}, Il12b (interleukin 12b) [NCBI Gene 16160] {aka Il-12b, Il-12p40, Il12p40, p40}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Tlr2 (toll-like receptor 2) [NCBI Gene 24088] {aka Ly105}
- **Diseases:** nephritis (MESH:D009393), hepatic (MESH:D056486), ankylosing spondyloarthritis (MESH:D013167), T1DM (MESH:D003922), cataracts (MESH:D002386), inflammatory cytokines (MESH:D000080424), IBD (MESH:D015212), NOD (MESH:D009765), ADs (MESH:D001327), -cell autoimmunity (MESH:D002292), UC (MESH:D003093), tissue injury (MESH:D017695), SLE (MESH:D008180), celiac disease (MESH:D002446), chronic (MESH:D002908), PBC (MESH:D008105), MS (MESH:D009103), immune dysregulation (OMIM:614878), psoriasis (MESH:D011565), epidermal hyperplasia (MESH:D006965), Hypothyroidism (MESH:D007037), connective tissue disease (MESH:D003240), bone fractures (MESH:D050723), hypertension (MESH:D006973), Inflammatory (MESH:D007249), arthritis (MESH:D001168), injury to (MESH:D014947), metabolic syndrome (MESH:D024821), critically ill (MESH:D016638), RA (MESH:D001172), juvenile idiopathic arthritis (MESH:D001171), CD (MESH:D003424), AD (MESH:D000544), colitis (MESH:D003092), axial spondylarthritis (MESH:D025241), dysbiosis (MESH:D064806), immune dysfunction (MESH:D007154), diabetic (MESH:D003920)
- **Chemicals:** LPS (MESH:D008070), steroids (MESH:D013256), prebiotic (MESH:D056692), GSH (MESH:D005978), NO (MESH:D009569), C-peptide (MESH:D002096), ROS (MESH:D017382), SCFA (MESH:D005232), acetate (MESH:D000085), inulin (MESH:D007444), hydrogen peroxide (MESH:D006861), AxSp (-), bile acids (MESH:D001647), mesalamine (MESH:D019804), fructooligosaccharides (MESH:C116580), MDA (MESH:D008315), butyrate (MESH:D002087)
- **Species:** Bifidobacterium animalis (species) [taxon 28025], Bacillus infantis (species) [taxon 324767], Limosilactobacillus reuteri (species) [taxon 1598], gut metagenome (species) [taxon 749906], Lactiplantibacillus plantarum (species) [taxon 1590], Clostridium butyricum (species) [taxon 1492], Streptococcus thermophilus (species) [taxon 1308], Lacticaseibacillus casei (species) [taxon 1582], Bifidobacterium longum (species) [taxon 216816], Bifidobacterium longum subsp. infantis (subspecies) [taxon 1682], Rodentia (rodent, order) [taxon 9989], Saccharomyces boulardii [taxon 252598], Lacticaseibacillus rhamnosus (species) [taxon 47715], Homo sapiens (human, species) [taxon 9606], Saccharomyces cerevisiae (baker's yeast, species) [taxon 4932], Lactobacillus johnsonii (species) [taxon 33959], Mus musculus (house mouse, species) [taxon 10090], Ligilactobacillus salivarius (species) [taxon 1624]

## Figures

7 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12943447/full.md

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Source: https://tomesphere.com/paper/PMC12943447