Immune dysfunction in patients with functional gastrointestinal disorders

Abstract There is increasing evidence for involvement of the immune system in functional gastrointestinal disorder (FGID), including onset after acute gastrointestinal infections, genotypes resulting in altered cytokine expression and abnormal presence of immune cells. Our aim was to assess cellular and humoral immune responses in (i) FGIDs, compared to healthy subjects and (ii) acute vs unspecified onset FGIDs. Lymphocytic [interleukin (IL)‐5, IL‐10, IL‐13 and interferon γ (IFN‐γ)] and monocytic [IL‐10, IL‐12, tumour necrosis factor (TNF)‐α] cytokine production was characterized at baseline and after stimulation with phytohemagglutinine and anti‐CD28 or lipopolysaccharide (LPS) in controls (n = 32), irritable bowel syndrome (IBS) (n = 30), functional dyspepsia (FD) (n = 23) and non‐cardiac chest pain (NCCP) (n = 15). Serum IL‐6 and IL‐10 concentrations were compared, and the immunophenotype was assessed using fluorescent‐activated cell sorter. Findings were compared for acute vs unspecified onset FGID. Compared to controls, stimulated lymphocyte expression of IL‐5 and IL‐13 was enhanced in IBS, FD and NCCP (all P < 0.05). Conversely, the stimulated monocytic IL‐12 and lymphocytic IL‐10 expression were reduced in IBS and FD, while IFN‐γ expression was also reduced in FD patients. Except for an increase in the numbers of CD3⁺CD45RA⁺CD45RO⁺ cells, no distinct cellular profile was detected. Patients with a presumed acute onset of their symptoms had higher serum IL‐10 levels and more CD3⁺CD45RA⁺CD45RO⁺ cells, while TNF‐α levels following stimulation with LPS were higher in FD patients reporting an acute onset. A shift towards a Th2 cytokine profile is present in FGID, while the cellular immunophenotype remains largely unchanged. Further research is indicated and could provide new therapeutic strategies for these disorders.     

Cortical deactivations during gastric fundus distension in health: visceral pain‐specific response or attenuation of ‘default mode’ brain function? A H215O‐PET study

Abstract Gastric distension activates a cerebral network including brainstem, thalamus, insula, perigenual anterior cingulate, cerebellum, ventrolateral prefrontal cortex and potentially somatosensory regions. Cortical deactivations during gastric distension have hardly been reported. To describe brain areas of decreased activity during gastric fundus distension compared to baseline, using data from our previously published study (Gastroenterology, 128, 2005 and 564). H₂¹⁵O‐brain positron emission tomography was performed in 11 healthy volunteers during five conditions (random order): (C₁) no distension (baseline); isobaric distension to individual thresholds for (C₂) first, (C₃) marked, (C₄) unpleasant sensation and (C₅) sham distension. Subtraction analyses were performed (in SPM2) to determine deactivated areas during distension compared to baseline, with a threshold of P_{uncorrected_voxel_level} < 0.001 and P_{corrected_cluster_level} < 0.05. Baseline–maximal distension (C₁–C₄) yielded significant deactivations in: (i) bilateral occipital, lateral parietal and temporal cortex as well as medial parietal lobe (posterior cingulate and precuneus) and medial temporal lobe (hippocampus and amygdala), (ii) right dorsolateral and dorso‐ and ventromedial PFC, (iii) left subgenual ACC and bilateral caudate head. Intragastric pressure and epigastric sensation score correlated negatively with brain activity in similar regions. The right hippocampus/amygdala deactivation was specific to sham. Gastric fundus distension in health is associated with extensive cortical deactivations, besides the activations described before. Whether this represents task‐independent suspension of ‘default mode’ activity (as described in various cognitive tasks) or an visceral pain/interoception‐specific process remains to be elucidated.     

Influence of abuse history on gastric sensorimotor function in functional dyspepsia

Abstract  Patients with functional gastrointestinal disorders have elevated rates of sexual or physical abuse, which may be associated with altered rectal sensorimotor function in irritable bowel syndrome. The aim was to study the association between abuse history and gastric sensorimotor function in functional dyspepsia (FD). We studied gastric sensorimotor function with barostat (sensitivity, compliance and accommodation) and gastric emptying test in 233 consecutive FD patients from a tertiary care centre (162 women, mean age 41.6 ± 0.9). Patients filled out self-report questionnaires on history of sexual and physical abuse during childhood or adulthood. Eighty-four patients (out of 198, 42.4%) reported an overall history of abuse [sexual and physical in respectively 30.0% (60/200) and 20.3% (42/207)]. FD patients reporting general as well as severe childhood sexual abuse have significantly lower discomfort thresholds during gastric distension [respectively 10.5 ± 0.4 vs 7.5 ± 1.0 mmHg above minimal distending pressure (MDP), P  = 0.014 and 10.5 ± 0.4 vs 6.6 ± 1.2 mmHg above MDP, P  = 0.007]. The corresponding intra-balloon volume was also significantly lower (respectively 579 ± 21 vs 422 ± 59 mL, P  = 0.013 and 579 ± 19 vs 423 ± 79 mL, P  = 0.033). Gastric accommodation was significantly more pronounced in patients reporting rape during adulthood (91 ± 12 vs 130 ± 40 mL, P  = 0.016). Abuse history was not associated with differences in gastric emptying. A history of abuse is associated with alterations in gastric sensorimotor function in FD. Particularly sexual abuse, rather than physical abuse, may influence gastric sensitivity and motor function.