Associations between fecal short-chain fatty acids, plasma inflammatory cytokines, and dietary markers with depression and anxiety: Post hoc analysis of the ENGAGE-2 pilot trial

Abstract

Background: The microbiome-gut-brain-axis (MGBA) is emerging as an important mechanistic link between diet and mental health. The role of significant modifiers of the MGBA, including gut microbial metabolites and systemic inflammation, in individuals comorbid with obesity and mental disorders, is under-investigated.

Objectives: This exploratory analysis examined associations among microbial metabolites-fecal SCFAs, plasma inflammatory cytokines, and diet with depression and anxiety scores in adults comorbid with obesity and depression.

Methods: Stool and blood were obtained from a subsample (n = 34) of participants enrolled in an integrated behavioral intervention for weight loss and depression. Pearson partial correlation and multivariate analyses determined associations among changes in fecal SCFAs (propionic, butyric, acetic, and isovaleric acids), plasma cytokines [C-reactive protein, interleukin 1 beta, interleukin 1 receptor antagonist (IL-1RA), interleukin 6, and TNF-α], and 35 dietary markers over 2 mo, and changes in SCL-20 (Depression Symptom Checklist 20-item) and GAD-7 (Generalized Anxiety Disorder 7-Item) scores over 6 mo.

Results: Changes in the SCFAs and TNF-α at 2 mo were positively associated (standardized coefficients: 0.06-0.40; 0.03-0.34) with changes in depression and anxiety scores at 6 mo, whereas changes in IL-1RA at 2 mo were inversely associated (standardized coefficients: -0.24; -0.05). After 2 mo, changes in 12 dietary markers, including animal protein, were associated with changes in SCFAs, TNF-α, or IL-1RA at 2 mo (standardized coefficients: -0.27 to 0.20). Changes in 11 dietary markers, including animal protein, at 2 mo were associated with changes in depression or anxiety symptom scores at 6 mo (standardized coefficients: -0.24 to 0.20; -0.16 to 0.15).

Conclusions: Gut microbial metabolites and systemic inflammation may be biomarkers of importance within the MGBA, linking dietary markers, such as animal protein intake, to depression and anxiety for individuals with comorbid obesity. These findings are exploratory and warrant replication.

Trial registration: ClinicalTrials.gov NCT03841682.

Keywords: animal protein; anxiety; depression; inflammatory cytokines; microbiome-gut-brain axis; obesity; short-chain fatty acids.