TOPLINE:

Probiotic supplementation decreased C-reactive protein (CRP) levels by 21.3% compared with placebo in patients with depression; a larger effect was seen in those with metabolic syndrome (MetS) or those using antidepressants.

METHODOLOGY:

• Researchers conducted a secondary analysis and assessed 88 participants with depressive disorders from a parent, 60-day, double-blind, randomised, placebo-controlled trial.
• Participants consumed a two-strain probiotic capsule containing Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-175 (3 × 10⁹ colony forming units) daily or a matching placebo.
• The primary outcome was a percentage change in CRP levels. A statistical measure, Cohen's d, was used to classify the effect size as small, medium, or large.
• Subgroup analyses evaluated CRP-lowering response on the basis of MetS (defined using the International Diabetes Federation criteria), chronic low-grade inflammation (CLGI) status, and antidepressant use.

TAKEAWAY:

• Probiotic supplementation significantly decreased overall CRP levels by 21.3% compared with placebo (P = .047), with a small effect size.
• The CRP-lowering effect of probiotics varied significantly on the basis of baseline factors: presence of MetS (P = .021), fasting blood glucose levels (P = .018), triglyceride levels (P = .044), alanine aminotransferase (ALT) cutoff value for fatty liver (P = .002), and antidepressant use (P < .001).
• The reduction in CRP levels was large and significant in patients with MetS (P = .045) and those with ALT values suggesting fatty liver (P = .001).
• No significant CRP-lowering effect was observed in participants not taking antidepressants or in those already classified with CLGI (CRP levels ≥ 3 mg/L).

IN PRACTICE:

"The intake of probiotics by people with depression may offer some improvement in lowering CRP levels, especially in patients with comorbid MetS, liver abnormalities, or the use of antidepressants," the authors wrote.

"The future potential of probiotic supplementation in the management of depression seems to be targeted at individuals with comorbidities of metabolic diseases, particularly suspected liver steatosis. Furthermore, patients treated with antidepressants may gain additional advantages from probiotic use, not only in terms of alleviating depression, but also in decreasing inflammation," they added.

SOURCE:

This study was led by Oliwia Gawlik-Kotelnicka, Medical University of Lodz, Łódź, Poland. It was published online on October 29, 2025, in Current Neuropharmacology.

LIMITATIONS:

This study was limited by the modest sample size, which may have particularly affected subgroup analyses. This study could have benefited from additional inflammatory markers beyond CRP, such as interleukin-6 and interleukin-1 beta. Potential confounders, such as unrecognised inflammatory conditions within the gastrointestinal tract, air pollution exposure, stressful life events, and genetic factors, were not fully accounted for. Additionally, complete data on antidepressant dosages and preintervention treatment periods were unavailable.

DISCLOSURES:

This research was funded by the Medical University of Lodz. The authors declared having no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.