Probiotics lower CRP in depression, meta-analysis finds, but other markers remain unclear

Probiotic supplementation may reduce levels of C-reactive protein (CRP) in people with depression, according to a systematic review and meta-analysis published in BMC Immunology. The analysis pooled results from eleven randomized controlled trials that examined how probiotics affected inflammatory markers in depressed patients, and it found a statistically significant reduction in CRP with probiotic use.

The pooled estimate for CRP showed a standardized mean difference of -0.55, with a 95% confidence interval of -1.07 to -0.04 and a P value of 0.036. This suggests that, across the included trials, probiotic supplementation was associated with a modest but statistically significant lowering of CRP, an inflammatory marker that previous studies have reported to be elevated in patients with depression.

However, the finding comes with an important caveat: the CRP results showed substantial statistical heterogeneity, with an I-squared value of 72.3% and a heterogeneity P value of 0.003. This means the individual trials varied considerably in their reported effects, so the pooled estimate should be interpreted with caution. A subgroup analysis indicated that probiotics appeared to exert more beneficial effects on CRP in interventions lasting eight weeks or longer, suggesting that duration of supplementation may matter.

For the other inflammatory markers examined, the picture was far less conclusive. The authors reported that substantial heterogeneity among the included studies precluded any meaningful pooled analysis of interleukin-6 (IL-6), which showed a standardized mean difference of -0.04 with a confidence interval spanning no effect, and tumor necrosis factor-alpha (TNF-α), which showed a standardized mean difference of -0.40 that did not reach statistical significance. Both markers displayed high heterogeneity, with I-squared values of 81.2% and 77.3% respectively.

Interleukin-1β (IL-1β) was the exception in terms of consistency: the trials were statistically homogeneous, with an I-squared of 0.00%, but the pooled estimate of 0.00 indicated no detectable effect of probiotics on this marker. In other words, the results for IL-1β were consistent across studies but consistently null.

The review was motivated by accumulating evidence that inflammation plays a role in the pathogenesis of depression. Previous studies have reported elevated levels of CRP, TNF-α, IL-6, and IL-1β in patients with depression, and probiotics have been proposed as a possible means of alleviating this inflammatory state. The authors set out to test this systematically by searching PubMed, Scopus, Web of Science, and Google Scholar for randomized controlled trials published up to April 2026.

The protocol was registered in PROSPERO, and only randomized controlled trials in subjects with depression were eligible for inclusion.

The authors concluded that probiotics could have ameliorative effects on CRP levels in patients with depression, while emphasizing that further studies are needed to investigate the real effect of probiotics on IL-6, IL-1β, and TNF-α levels.

For now, the most defensible takeaway is a narrow one: in this meta-analysis of randomized trials, probiotic supplementation was associated with significantly reduced CRP in depressed patients, particularly in trials lasting at least eight weeks, while the evidence for effects on interleukins and TNF-α remains inconclusive pending better-designed and more homogeneous studies.

Subject of Research: The effect of probiotic supplementation on inflammatory markers in patients with depression

Article Title: Do probiotics reduce systemic inflammation in depression? A systematic review and meta-analysis

Article References: Lan, X., Xiang, J., Li, R., Wong, G., & Xia, Y. (2026). Do probiotics reduce systemic inflammation in depression? A systematic review and meta-analysis. BMC Immunology. https://doi.org/10.1186/s12865-026-00911-y

Image Credits: AI Generated

DOI: 10.1186/s12865-026-00911-y

Keywords: probiotics, depression, C-reactive protein, systematic review, meta-analysis, inflammation, IL-6, TNF-alpha, IL-1beta, randomized controlled trials, BMC Immunology, reduce