Background Patients suffering from post-infectious irritable bowel syndrome (PI-IBS) develop gastrointestinal symptoms after an enteric infection. It has been suggested that changes in the intestinal microbial composition, a low-grade mucosal inflammation and also psychological distress are important factors in the PI-IBS pathophysiology. In this study, we investigated the potential association between these factors. Methods Mucosal biopsies and faecal samples were collected from 13 PI-IBS patients and 16 healthy controls after signing informed consent. The study was approved by the Medical Ethics Committee of Uppsala University/Örebro University, Sweden, as well as registered at ClinicalTrial.gov NCT01787253. Global bacterial composition was determined by generating 16S rRNA amplicons that were examined by phylogenetic microarray hybridization, principal component and redundancy analysis. Previously reported lymphocyte proportions (1) were correlated with the microbiota composition and HADS (Hospital anxiety and depression scale) scores. Results Mucosal microbiota diversity was negatively correlated with the number of lamina propria lymphocytes (p < 0.05). In addition, mucosal microbiota diversity positively correlated with the CD8+ CD45RA+ intraepithelial lymphocyte proportion (p < 0.005). Faecal microbiota diversity was negatively correlated to the HADS scores (p < 0.05). Conclusions This study revealed a significant association between specific lymphocyte subsets and the microbial composition and diversity in colonic mucosa from PI-IBS patients. In addition, the fecal microbiota composition negatively correlated with measures of psychological distress. These findings suggest an association between alterations in intestinal microbiota and the mucosal adaptive immune response as well as psychological state. (1) Sundin et al., Scand J Gastroenterol. 2014;49(9):1068-75.