Micro‐inflammation in functional dyspepsia: A systematic review and meta‐analysis

Abstract

Functional dyspepsia (FD) is a gastrointestinal disorder of unknown etiology. Although micro-inflammation appears to be important in the pathogenesis, studies evaluating immune activation in FD have been inconsistent. A systematic review of literature and meta-analysis was performed to compare immunologic cell counts and cytokine levels in the mucosa and peripheral blood of individuals with FD and healthy controls. PubMed, Embase, and the Cochrane library were searched. Data on immunologic cell counts and cytokines levels among individuals with FD and control groups were extracted and compared by calculating standard mean differences (SMD). Thirty-seven studies met the inclusion criteria. Mast cell (SMD = 0.94, 95%CI 0.26-1.62, P = .007) and eosinophil counts (SMD = 0.36, 95%CI 0.06-0.68, P = .03) in the stomach were increased, among individuals with FD compared to controls. Similarly, mast cell (SMD = 0.66, 95%CI 0.20-1.13, P = 0.005) and eosinophil (SMD = 0.95, 95%CI 0.66-1.24; P < .001) counts in the duodenum were also increased in those with FD compared to controls. In a subgroup analysis, elevated eosinophil counts in the duodenum were observed in both post-prandial distress syndrome (SMD = 0.97, 95%CI 0.46-1.47, P = .0002) and epigastric pain syndrome subtypes (SMD = 1.16, 95%CI 0.48-1.83, P = .0008). No differences in mucosal intraepithelial lymphocyte, enterochromaffin cell, and neutrophil counts, as well as, peripheral interlukin-6 (IL-6) and IL-10 levels were observed among individuals with FD and controls. Micro-inflammation in the form of local immune cell infiltration, particularly eosinophils and mast cells, characterizes the pathogenesis of FD.

Biliary Dyskinesia in Children and Adolescents: A Mini Review

“…It is also possible that chronic cholecystitis and biliary dyskinesia are two distinct conditions without overlap and that the differentiation can only be made definitively after cholecystectomy. Additionally, or alternatively, biliary dyskinesia might be associated with mucosal mast cells, also analogous to what has been reported with functional dyspepsia and irritable bowel syndrome (50,51). Compared to autopsy controls, we have previously demonstrated a >9fold increase in gallbladder mast cell density in children with biliary dyskinesia (52).…”

Degranulated Eosinophils Contain More Fine Nerve Fibers in the Duodenal Mucosa of Patients With Functional Dyspepsia

“…Since the description by Toukan et al 24 of infiltration of the duodenum by eosinophils in patients with FD, several studies have demonstrated significant infiltration of eosinophils into the upper GI tract in patients with FD. 16,[26][27][28][29] In a Swedish population-based study, the degree of infiltration of eosinophils and mast cells into the duodenum was sampled randomly in 51 patients with FD and 41 patients with IBS. The results suggested that the number of eosinophils, but not mast cells, is increased significantly in the duodenum of patients with FD, and that the number of mast cells are increased significantly in patients with IBS.…”

“…In another cohort, the duodenal eosinophilia was related with early satiety/fullness, not epigastric pain, 27,34 however, other recent studies showed no significant differences between EPS and PDS. 29,35 In the latter, a significant amount of eosinophils and mast cells infiltrated the submucosal layer combined with altered submucosal ganglionic architecture and accompanied by decreased calcium responses to depolarization in FD. 35 The contribution of the submucosal nerve plexus to normal gastric motility is probably minimal because gastric submucosa contains few intrinsic primary afferent neurons and the intrinsic reflexes are poorly developed.…”

Functional dyspepsia: from pathogenesis to therapeutic aspects

“…Подтверждением этому являются исследования, в которых сообщается об увеличении количества тучных клеток и эозинофилов в биоптатах слизистой оболочки двенадцатиперстной кишки, что подчеркивает потенциальную роль воспалительных механизмов в патогенезе ФД [29]. Так, в недавнем метаанализе, обобщившем результаты 37 исследований, было продемонстрировано, что у пациентов с ФД по сравнению с группой контроля отмечается увеличение количества тучных клеток (стандартизованная разность средних (СРС) = 0,66, 95% ДИ 0,20-1,13, p = 0,005) и эозинофилов (СРС = 0,95, 95% ДИ 0,66-1,24; p < 0,001) в слизистой оболочке двенадцатиперстной кишки [30]. Данные клетки являются эффекторными и в случае активации вырабатывают большое количество цитокинов, способных оказывать влияние на чувствительность нервных окончаний слизистой оболочки, тем самым индуцируя возникновение феномена ВГ или моторнотонических нарушений гастродуоденальной зоны (описанных выше).…”

“…С учетом появления все большего количества работ и экспертных мнений касательно роли в генезе ФД субклинического воспаления двенадцатиперстной кишки на фоне нарушения эпителиальной проницаемости на сегодняшний день активно изучаются терапевтические возможности назначения лекарственных средств, обладающих цитопротективным действием по отношению к слизистой оболочке ЖКТ [12,28,49]. В настоящий момент доказательная база эффективности гастропротективных препаратов при ФД продолжает активно формироваться.…”