The duodenal mucosa associated microbiome, visceral sensory function, immune activation and psychological comorbidities in functional gastrointestinal disorders with and without self-reported non-celiac wheat sensitivity.

Frequently, patients with functional gastrointestinal disorders (FGIDs) report intolerance of wheat products. We compared gastrointestinal symptoms, sensory function, psychiatric comorbidities, gut-homing immune cells, and duodenal mucosa-associated microbiome (d-MAM) in FGID patients and controls with and without self-reported wheat sensitivity (SR-NCWS). We recruited 40 FGID patients and 20 controls referred by GPs for treatment. Gastrointestinal/extraintestinal symptoms, visceral sensory function, psychological comorbidities, and SR-NCWS were assessed in a standardized approach. Peripheral gut homing T-cells (CD4⁺α4⁺β7⁺CCR9⁺/CD8⁺α4⁺β7⁺CCR9⁺) were quantified, and the d-MAM was assessed by DNA sequencing for 46 subjects. Factors of bacterial genera were extracted utilizing factor analysis with varimax rotation and factors univariately associated with FGID or SR-NCWS included in a subsequent multivariate analysis of variance to identify statistically independent discriminators. Anxiety scores (p &lt; .05) and increased symptom responses to a nutrient challenge (p &lt; .05) were univariately associated with FGID. Gut homing T-cells were increased in FGID patients with SR-NCWS compared to other groups (p all &lt;0.05). MANOVA revealed that anxiety (p = .03), visceral sensory function (p = 0.007), and a d-MAM factor comprise members of the <i>Alloprevotella, Prevotella, Peptostreptococcus, Leptotrichia</i>, and <i>Veillonella</i> lineages were significantly (p = .001) associated with FGID, while gut homing CD4⁺α4⁺ β7⁺CCR9⁺ T-cells were associated (p = .002) with SR-NCWS. Compared to controls, patients with and without SR-NCWS show that there are shifts in the amplicon sequence variants within specific bacterial genera between the FGID subgroups (particularly <i>Prevotella</i> and <i>Streptococcus</i>) as well as distinct bacterial taxa discriminatory for the two different FGID subtypes. Compared to controls, both FGID patients with and without SR-NCWS have an increased symptom response to a standardized nutrient challenge and increased anxiety scores. The FGID patients with SR-NCWS - as compared to FGID without SR-NCWS (and controls without SR-NCWS) - have increased gut homing T-cells. The d-MAM profiles suggest species and strain-based variations between the two FGID subtypes and in comparison to controls.