The densities of enteroendocrine cells are abnormal in patients with irritable bowel syndrome (IBS); however, they tend to change toward normal levels in stomach, ileum, and colon following dietary guidance. The aim was to identify the types of duodenal enteroendocrine cells affected after receiving dietary guidance in the same group of patients with IBS. Fourteen patients with IBS and 14 control subjects were included. The patients received three sessions of dietary guidance. Both groups underwent gastroscopies at baseline, and again for the patients after 3-9 months (median, four months) from receiving dietary guidance. Tissue biopsies were collected from the descending part of the duodenum and were immunostained for all the types of enteroendocrine cells and were then quantified by using computerized image analysis. Using the Kruskal-Wallis non-parametric test with Dunn's test as a post-test, the results showed a significant difference in the secretin cell densities between control subjects and patients with IBS prior to and following dietary guidance ( P = 0.0001 and 0.011, respectively). The corresponding P values for cholecystokinin (CCK) cell densities were 0.03 and 0.42, respectively; gastric inhibitory peptide (GIP) cell densities were 0.06 and 0.43, respectively; serotonin cell densities were <0.0001 and 0.002, respectively; and for somatostatin cell densities were <0.0001 and 0.052, respectively. The Paired t-test showed a significant difference only in the serotonin ( P = 0.03) and somatostatin ( P < 0.0001) cell densities between IBS patients prior to and following dietary guidance. The changes in the cell densities of secretin, CCK, and GIP were not significant between IBS patients prior to and following dietary guidance. In conclusion, the densities of several duodenal enteroendocrine cells in IBS patients changed toward the values measured in control subjects following dietary guidance. The changes in serotonin and somatostatin cell densities may have contributed to the improvements in IBS symptoms, particularly pain and diarrhea. Impact statement Several contributing factors to the symptomology of irritable bowel syndrome (IBS) have been identified, such as abnormal densities of enteroendocrine cells and diet; however, the interactions between these factors have not been studied yet. The current study aims at exploring the dynamic changes between these two factors by studying the effect of using low fermentable oligo-, di-, monosaccharides and polyol (FODMAP) diet (known to improve IBS symptoms) through dietary guidance on the enteroendocrine cell densities in the duodenum. The findings showed that the densities of different enteroendocrine cells in the duodenum were abnormal before the patients received dietary guidance and tend to change/normalize after receiving guidance, which may have contributed in improving the symptoms of IBS. These findings highlight the importance of enteroendocrine cells in IBS pathophysiology and the mechanism behind the positive effect of low FODMAP dietary guidance in improving IBS symptoms and its usage as first step in the line of IBS management.