The Interplay Between Depression, Probiotics, Diet, Immunometabolic Health, the Gut, and the Liver—A Secondary Analysis of the Pro-Demet Randomized Clinical Trial

(1) Background: Depression, metabolic alternations, and liver diseases are highly comorbid. Studies have shown that probiotics might be helpful in the treatment of the above-mentioned states. The aim of this secondary analysis was to search for possible predictors of probiotics' efficacy on liver-related outcome measures. (2) Methods: Data from 92 subjects from a randomized clinical trial on the effect of probiotics on depression were analyzed. The shift in liver steatosis and fibrosis indices was assessed in the context of baseline immunometabolic, psychometric, dietary, and intestinal permeability factors. Correlation analysis and linear regression models were used. (3) Results: A total of 30% of the variance of the improvement in the score of the aspartate transferase to platelet ratio index was explained by probiotic use, higher pre-intervention triglycerides, cholesterol, C-reactive protein levels, increased cereal intake, and a lower consumption of sweets. Then, the model of the change in alanine transferase indicated that probiotics were efficient when used by subjects with higher basal levels of intestinal permeability markers. (4) Conclusions: Probiotics being used along with a healthy diet may provide additional benefits, such as decreased cardiovascular risk, for patients with measures consistent with the immunometabolic form of depression. Probiotic augmentation may be useful for liver protection among subjects with a suspected "leaky gut" syndrome. ClinicalTrials.gov: NCT04756544.