CBT led to significant reductions in social anxiety symptoms alongside increases in plasma butyric, isobutyric, propionic, and valeric acids, with isobutyric acid statistically significantly lower in SAD patients relative to healthy controls before treatment.
Key Findings
Results
CBT led to significant reductions in social anxiety symptoms that were sustained at 36-month follow-up.
46 individuals with SAD underwent nine weeks of internet-delivered CBT.
Social anxiety symptom assessments were conducted twice at pre-treatment, once at post-treatment, and once at 36-month follow-up.
Effects on social anxiety symptoms were described as sustained at the 36-month follow-up timepoint.
Generalized additive mixed models were used to assess longitudinal changes with CBT.
Results
Plasma concentrations of butyric, isobutyric, propionic, and valeric acids increased after CBT.
Nine SCFAs were measured using liquid chromatography-mass spectrometry.
Increases in these four SCFAs were observed following nine weeks of internet-delivered CBT.
Trajectories of SCFA changes were 'predominantly explained by time rather than individual variability.'
Data completeness was greater than 80% across measurement timepoints.
Results
Isobutyric acid was statistically significantly lower in SAD patients compared to healthy controls before CBT.
Healthy controls (n = 42) underwent two SCFA assessments approximately 11 weeks apart.
Linear mixed models were used to assess patient-control differences.
The difference in isobutyric acid was specific to the pre-treatment timepoint.
This finding was described as 'statistically significantly lower in SAD patients, relative to healthy controls.'
Methods
The study design included test-retest reliability assessment for plasma SCFA measurements.
Intraclass correlation coefficients were used to assess test-retest reliability.
Healthy controls had two SCFA assessments 11 weeks apart, providing a comparator for reliability analysis.
Patients had two pre-treatment SCFA assessments, also enabling reliability estimation.
Plasma SCFA concentrations were measured using liquid chromatography-mass spectrometry.
Discussion
The authors note that lifestyle factors were not assessed but may have contributed to observed long-term metabolic changes.
This limitation was acknowledged explicitly in the abstract.
The study followed patients up to 36 months, a period during which lifestyle changes could occur independently of CBT.
The findings were characterized as 'initial evidence' linking sustained therapeutic benefits of CBT to alterations in circulating microbial metabolites.
The authors propose SCFAs as 'key microbial metabolites that may mediate microbiota-brain communication.'
Results
The study found that SAD is associated with altered circulating microbial metabolites as indexed by lower isobutyric acid at pre-treatment.
Before CBT, isobutyric acid was the only SCFA reported as statistically significantly different between SAD patients and healthy controls.
The patient group comprised 46 individuals with SAD.
The healthy control group comprised 42 individuals.
These findings were framed within the broader context of emerging evidence linking gut microbiota to variation in social behavior and anxiety.
What This Means
This research suggests that people with social anxiety disorder (SAD) have lower levels of a gut-derived compound called isobutyric acid in their blood compared to people without the disorder. Isobutyric acid is a short-chain fatty acid (SCFA) — a type of molecule produced when gut bacteria break down dietary fiber. The study tracked 46 people with SAD through nine weeks of internet-based cognitive behavioral therapy (CBT) and measured nine different SCFAs in their blood before treatment, after treatment, and again three years later, comparing them to 42 healthy individuals.
After completing CBT, patients showed meaningful improvements in social anxiety symptoms that lasted through the three-year follow-up. Alongside these mental health improvements, blood levels of four SCFAs — butyric acid, isobutyric acid, propionic acid, and valeric acid — increased over the course of treatment and follow-up. Notably, these changes in SCFA levels appeared to be driven primarily by time passing rather than by differences between individual patients.
This research suggests a possible connection between the gut microbiome and anxiety treatment — specifically, that successful therapy for social anxiety may be accompanied by changes in gut-derived metabolites circulating in the bloodstream. However, the study could not rule out that lifestyle changes over the three-year period (such as diet or exercise) contributed to the shifts in SCFA levels, since these factors were not tracked. The findings are considered preliminary and point to the gut-brain axis as a potentially interesting area for understanding how psychological treatments work.
Cai W, Stiernborg M, Wolthon A, Landberg R, Manzouri A, Furmark T, et al.. (2026). Plasma short-chain fatty acid concentrations in social anxiety disorder and changes after cognitive behavioral therapy.. Translational psychiatry. https://doi.org/10.1038/s41398-026-04134-y