Pre-analytical considerations in the interpretation of plasma SCFA profiles

We read with great interest the study by Cai et al. [ 1 ], reporting longitudinal changes in plasma short-chain fatty acid (SCFA) concentrations in patients with social anxiety disorder (SAD) following internet-delivered cognitive behavioral therapy (CBT). This is, to our knowledge, a unique longitudinal investigation of circulating SCFA profiles across an extended treatment course in SAD. The two-baseline design that incorporates healthy controls, the use of generalized additive mixed models, and retention exceeding 80% at 36 months are notable methodological strengths. The finding that isobutyric acid was significantly lower in SAD patients than in matched healthy controls at both pre-treatment assessments is particularly compelling, as convergence across two independent time points lends robustness to this group difference.