Luis Charúa-Guindic

Differences in Gastrointestinal Symptoms According to Gender in Rome II Positive IBS and Dyspepsia in a Latin American Population

OBJECTIVES:Irritable bowel syndrome (IBS), constipation, and bloating are more prevalent in women than men, but gender differences associated with dyspepsia are inconsistent.The aim of this study was to determine gender differences in the prevalence of symptoms diagnostic for functional gastrointestinal disorders (FGIDs) in subjects with IBS and dyspepsia, as well as in controls in Mexico.METHODS:A database of 1,021 subjects (61% women) who completed the Rome II Modular Questionnaire (RIIMQ) in Spanish Mexico was analyzed. Gender differences in the frequency of all symptoms included in the RIIMQ between those fulfilling criteria for IBS (28.9%), dyspepsia (4.0%) and controls without any FGIDs (38.2%) were studied. Subjects fulfilling criteria only for other FGIDs were excluded.RESULTS:There were higher proportions of women with IBS (67.8%) and dyspepsia (85.4%) compared with the control group (55.9%) (P<0.001). In IBS, women more frequently reported changes in the number of bowel movements (BMs) associated with the onset of abdominal discomfort/pain, fewer than three BMs/week and abdominal fullness/bloating/swelling than men. Men with IBS more frequently reported swallowing air to belch and abdominal pain that improved after a BM than women. In controls, burping and hard or lumpy stools were both more frequent in men.CONCLUSIONS:In Mexico, gender differences in FGIDs exist, with both IBS and dyspepsia being more common in women than men. In IBS, symptoms related to constipation and bloating were more common in women, but the dyspepsia group was too small to draw any conclusions. Finally, this is the first study to report that belching is more common in men than women controls not fulfilling criteria for any FGID.

Maturation Phenotype of Peripheral Blood Monocyte/Macrophage After Stimulation with Lipopolysaccharides in Irritable Bowel Syndrome.

Background/Aims Abnormal immune regulation and increased intestinal permeability augmenting the passage of bacterial molecules that can activate immune cells, such as monocytes/macrophages, have been reported in irritable bowel syndrome (IBS). The aim was to compare the maturation phenotype of monocytes/macrophages (CD14+) from IBS patients and controls in the presence or absence of Escherichia coli lipopolysaccharides (LPS), in vitro. Methods Mononuclear cells were isolated from peripheral blood of 20 Rome II-IBS patients and 19 controls and cultured with or without LPS for 72 hours. The maturation phenotype was examined by flow cytometry as follows: M1-Early (CD11c+CD206−), M2-Advanced (CD11c−CD206+CX3CR1+); expression of membrane markers was reported as mean fluorescence intensity (MFI). The Mann-Whitney test was used and significance was set at P < 0.05. Results In CD14+ cells, CD11c expression decreased with vs without LPS both in IBS (MFI: 8766.0 ± 730.2 vs 12 920.0 ± 949.2, P < 0.001) and controls (8233.0 ± 613.9 vs 13 750.0 ± 743.3, P < 0.001). M1-Early cells without LPS, showed lower CD11c expression in IBS than controls (MFI: 11 540.0 ± 537.5 vs 13 860.0 ± 893.7, P = 0.040), while both groups showed less CD11c in response to LPS (P < 0.01). Furthermore, the percentage of “Intermediate” (CD11c+CD206+CX3CR1+) cells without LPS, was higher in IBS than controls (IBS = 9.5 ± 1.5% vs C = 4.9 ± 1.4%, P < 0.001). Finally, fractalkine receptor (CX3CR1) expression on M2-Advanced cells was increased when treated with LPS in controls but not in IBS (P < 0.001). Conclusions The initial phase of monocyte/macrophage maturation appears to be more advanced in IBS compared to controls. However, the decreased CX3CR1 in patients with IBS, compared to controls, when stimulated with LPS suggests a state of immune activation in IBS.

Su2065 Peripheral Blood Monocyte/Macrophage Maturation Phenotype in IBS After Stimulation With LPS

Background: IBS pathophysiology remains poorly understood; however, recent findings support a state of immune activation characterized by increased TLR expression and intestinal epithelial diffusion of bacterial molecules in the gut, at least in a subgroup of patients. Aims: We sought to relate these factors in IBS, by analyzing the maturation phenotype of peripheral blood monocyte/macrophage cells, according to the intestinal maturation-process [M1: initial stage (CD11c+CD206-), M2: advanced maturation (CD11c-CD206+CX3CR1+)] when stimulated with E. coli-Lipopolysaccharides (LPS). Methods: 21 IBS-Rome II patients and 19 controls were studied in Mexico City. Isolated peripheral blood mononuclear cells (PBMCs) were cultured for 72 hours with and without E. Coli-LPS, and the polarization phenotype of monocytes/macrophages (CD14+) was investigated by flow cytometry. Also, levels of Transforming Growth Factor-beta 1 (TGF-β1), a M2 cell-derived cytokine involved in tissue healing, was investigated by enzyme-linked immunosorbent assay (ELISA), in cultures supernatant. TheMann-Whitney U-test was used, considering a p<0.05 as significant. Results: LPS-stimulated CD14+ cells displayed lower CD11c expression levels in both IBS patients and controls than in the unstimulated condition (8766±730.2 vs 12920±949.2, p<0.001 and 8233±613.9 vs 13750±743.3, p<0.001; respectively), but there were no differences between the IBS and controls. Also, M1 (CD11c+CD206-) unstimulated cells showed lower CD11c expression in IBS vs controls (11540±537.5 vs 13860±893.7, p=0.038); while a decrease in both IBS (11540±537.5 vs 7940±537.7, p<0.001) and controls (13860±893.7 vs 8091±574.5, p<0.001) was observed after LPS-stimulation. In addition the percentage of CD11c+CD206+CX3CR1+ cells was higher in IBS vs controls (9.5±1.5% vs 4.9±1.4%) without LPS stimulation. When comparing the unstimulated vs LPS-stimulated condition, the CX3CR1 expression level in M2-cells increased in controls but not in IBS (71.1±89.5 vs -151.7±31.1, p<0.001). Finally, no differences were observed in TGF-β1 levels of both IBS vs controls (3.77±0.39 vs 3.61±0.14), even after stimulation with LPS (3.58±0.18 vs 3.57±0.13). Conclusions: The data suggests that the initial phase of maturation of monocytes/ macrophages is faster in IBS vs controls. However, the absence of an increase in CX3CR1 expression in response to LPS in IBS, suggests an altered immnoregulatory response in patients with this disorder. Nevertheless, lack of differences in TGF-β1 between the IBS and controls supports the hypothesis that CD11c-CD206+ CX3CR1+ cells in IBS are not related to a healing response but to altered immunoregulatory functions in the presence of PAMPs. Funded by grant PAPIIT IN210010, DGAPA-Universidad Nacional Autonoma de Mexico (UNAM). Oscar Rodriguez-Fandino was funded by grant CONACyT No. 336205.