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

2025-10-29
Current neuropharmacology 23

PubMed: 41177800
DOI: 10.2174/011570159x371175251002220658

Study Design

Type: Randomized Controlled Trial (RCT)
Sample size: n = 88
Population: adult patients with depressive disorders
Methods: a two-arm, 60-day, prospective, randomized, double-blind, controlled study; probiotic formulation contained Lactobacillus helveticus Rosell®-52 and Bifidobacterium longum Rosell®-175

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.

Research Insights

Supplement	Dose	Health Outcome	Effect Type	Effect Size	Source
Bifidobacterium longum Rosell-175	—	No Change in Inflammation Markers	Neutral	Small	View source There were no significant differences in complete blood countderived parameters or in tumor necrosis factor-α levels.
Bifidobacterium longum Rosell-175	—	Reduced C-Reactive Protein Levels	Beneficial	Small	View source 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).
Lactobacillus helveticus Rosell-52	—	No Significant Change in Tumor Necrosis Factor Alpha Levels	Neutral	Small	View source There were no significant differences in complete blood countderived parameters or in tumor necrosis factor-α levels.
Lactobacillus helveticus Rosell-52	—	Reduced C-Reactive Protein Levels	Beneficial	Small	View source 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).