Probiotics Decrease C-Reactive Protein Levels in Depression Depending on Metabolic Syndrome Presence or Antidepressant Treatment – Secondary Results of a Randomized Clinical Trial

Curr Neuropharmacol. 2025 Oct 29. doi: 10.2174/011570159X371175251002220658. Online ahead of print.

ABSTRACT

INTRODUCTION: There is a need to search for new treatment options not only for depression but also for its concomitant diseases. Particularly, depression and metabolic health abnormalities often coexist, while inflammation and microbiota imbalance may play a part in their pathophysiological overlap. Thus, trials of interventions targeting the microbiota may result in establishing a safe adjunctive treatment option. This secondary analysis aimed to assess the effect of a probiotic formulation on inflammatory parameters in adult patients with depressive disorders depending on baseline clinical and immunometabolic characteristics.

METHOD: The parent trial was a two-arm, 60-day, prospective, randomized, double-blind, controlled study. The probiotic formulation contained Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175. The change in inflammatory parameters after the intervention in the context of baseline lifestyle, clinical, metabolic, and inflammatory parameters was assessed.

RESULTS: In per-protocol analysis, data from 88 participants were finally analyzed. Probiotic supplementation decreased the levels of C-reactive protein (CRP) compared to placebo by 21.3% with a small effect size (p = .047, d = .249). There were no significant differences in complete blood countderived parameters or in tumor necrosis factor-α levels. The impact of probiotics was different when stratified by baseline metabolic syndrome (MetS) presence, liver steatosis non-invasive biomarkers, chronic low-grade inflammation status, and antidepressant use.

DISCUSSION: 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 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.

CONCLUSION: Due to the preliminary character of our results, we emphasize the need for future studies in this area.

CLINICALTRIALS: gov identifier: NCT04756544.

PMID:41177800 | DOI:10.2174/011570159X371175251002220658