Reproducible microbiome composition associations with anxiety are not mediated by short chain fatty acids or indoles

Raw data re: Reproducible microbiome composition associations with anxiety are not mediated by short chain fatty acids or indoles<br>Gut bacteria may influence the brain via microbial metabolites (i.e. short-chain fatty acids (SCFAs) and indoles) or altering levels of neuromodulators (i.e. serotonin, GABA, cortisol and kynurenine). Meta-analyzing data from two cohorts (WebEx: n = 37 and Omega 3/Fiber: n = 58) and published literature (n = 60), we aimed to identify bacterial taxa reproducibly associated with anxiety. We further investigated the role of serum levels of SCFAs and indoles on anxiety and the links between anxiety-associated operational taxonomic units (OTUs) and neuromodulators involved in anxiety. Gut microbiota was characterized using 16S rRNA sequencing in stool samples. OTU data were transformed and normalized. Serum metabolites were measured using tandem mass spectrometry. We identified reproducible microbiome associations of anxiety with Escherichia-Shigella (fixed-effect beta (95% CI) = 0.29 (0.14, 0.45), False Detection Rate (FDR)-adj. p =1.4 x 10−3), Christensenellaceae R-7 group (fixed-effect beta (95% CI) = -0.28 (-0.44, -0.12), FDR-adj. p = 4.2 x 10−3) and Prevotellaceae NK3B31 group (fixed-effect beta (95% CI) = -0.25 (-0.42, -0.09), FDR-adj. p = 1.47 x 10−2). We found no significant associations between anxiety and gut-derived metabolites nor between anxiety-associated bacteria and anxiety-related markers after meta-analysis and correcting for multiple testing. Overall, several reproducible anxiety-microbiome associations were identified that were not mediated by SCFAs, indoles or anxiety-related markers, suggesting other mechanisms are at play. Given the known associations with health for the Christensenellaceae genus and the pathogenic nature of E. Shigella, our findings suggest that these taxa may be considered as biomarkers of anxiety in humans.<br>All participants provided written informed consent. For WebEx, ethical approval was obtained from the Research Ethics Committee (ref:18/EM/0154) and the Health Research Authority (protocol no: 18021) and the trial is registered under the clinicaltrials.gov database (NCT03545048). The Omega 3/Fiber trial was approved by the West Midlands Black Country Research Ethics Committee (18/WM/0066) and is registered under the clinicaltrials.gov database (NCT03442348).<br>