133: Effect of Probiotics on the Levels of Neuroendocrine Biomarkers – A Systematic Review & Meta-Analysis

Statement of Purpose, Innovation or Hypothesis: The effects of probiotics have been investigated for a variety of biomarkers in both healthy individuals for acute and chronic stress and patients with various diseases. Results are inconsistent and vary greatly across different study populations, age groups, number of bacterial strains administered, duration of treatment and geographical locations. There is a dearth of evidence that can capture the diverse demographic spectrum and enhance the generalizability of findings. We explored whether the administration of probiotics alone alters neuroendocrine biomarkers’ levels.

Description of Methods & Materials: This systematic review and meta-analysis searched seven databases from inception until March 18, 2024, for RCTs assessing the effect of probiotics on 8 neuroendocrine biomarkers – cortisol, BDNF, DHEA, alpha-amylase (AA), ACTH, oxytocin, norepinephrine, and epinephrine, across all age groups and with no specific medical condition requirement (Figure 1). The standardized mean difference, along with 95 % CI, was calculated for each study. Considering inherent clinical heterogeneity, we used a random-effects model to report the pooled estimate with 95 % CI. Heterogeneity (I²) and 95 % prediction interval were also reported. Heterogeneity was explored using subgroup analysis based on number of bacterial strains given (≤3 or >3), treatment duration (≤ 8 or > 8 weeks), study population (diseased or healthy), site of participant recruitment (hospital or community or university or database), region (Asia/Europe/USA/rest), and risk of bias. Sensitivity analyses included an outlier detection, influence analysis, leave-one-out meta-analyses, and trim-fill meta-analysis. The certainty of evidence was evaluated using the GRADE approach.

Data & Results: Screening through 6700 records yielded 43 RCTs, including 3253 participants. Probiotics did not cause significant alterations in biomarker levels when all studies were analysed collectively for each outcome measure, but high heterogeneity rendered the evidence inconclusive (Table 1). On subgroup analyses, heterogeneity remained very high in each subgroup for every outcome. Following sensitivity analyses, a considerable reduction in heterogeneity and narrowing of CI was observed, resulting in the inclusion of 14 studies for cortisol, 7 for BDNF, and 5 each for DHEA and AA in the final analysis (Table 1). Probiotics did not alter any biomarker levels significantly. The certainty of the evidence was high for cortisol, BDNF, and DHEA, moderate for AA, and very low for oxytocin and ACTH in this analysis.

Interpretation, Conclusion or Significance: The comprehensive analysis of a substantial number of RCTs reveals that probiotics do not significantly alter neuroendocrine biomarker levels, irrespective of health status, geographical location, treatment duration, and the number of bacterial strains administered. These findings are robust and supported by sensitivity analyses. However, evidence remains inconclusive for oxytocin and ACTH due to limited data availability. Our analysis challenges the findings of previous studies that probiotics perform their regulatory role by modulating cortisol, BDNF, DHEA and AA levels in various disease settings.

Disclosures: None

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Additional Information/Authors: None