The effect of probiotics, parabiotics, synbiotics, fermented foods and other microbial forms on immunoglobulin production: a systematic review and meta-analysis of clinical trials

Systematic review and meta-analysis of adult clinical trials in participants older than 18 years. Included populations were diverse and comprised healthy adults, athletes, and people with allergic symptoms or metabolic syndrome; critically ill, HIV, cancer, pregnant, and lactating populations were excluded from the main analyses.

Clinical trials of oral microbial-form interventions, including probiotics, parabiotics, synbiotics, fermented foods, and other microbial forms, were pooled across studies. The review compared these active interventions against control conditions and examined their effects on immunoglobulin outcomes; no single standardized dose or duration was available across the pooled trials.

Pooled microbial supplementation produced a small increase in salivary IgA secretion rate, but most other immunoglobulin outcomes were not significantly changed. Salivary IgA secretion rate improved in 8 studies (N=452; SMD 0.21, 95% CI 0.02 to 0.39; p=0.03), but the effect was no longer significant after excluding inactivated probiotic studies (SMD 0.16, 95% CI -0.11 to 0.44). No significant effects were seen for salivary IgA concentration (N=1651; SMD 0.11, 95% CI -0.02 to 0.24), IgE, Japanese cedar pollen-specific IgE, IgG, or IgM; serum IgA was significant only when healthy and ill participants were pooled (N=1205; SMD 0.32, 95% CI 0.08 to 0.55; p=0.009).

Findings were driven by heterogeneous interventions, populations, and outcome definitions, with several analyses showing substantial heterogeneity. The salivary IgA benefit was sensitive to inclusion of non-viable probiotic studies, and confidence was low for several outcomes. Geography and study quality also appeared to influence results, limiting generalizability.