Background & Aims

Changes in intestinal microbiota, stress and inflammation are factors known to be relevant in the pathogenesis of pain and further symptoms in disorders of gut-brain interaction (DGBI), previously designated as functional gastrointestinal disorders (1). The same factors are also implicated in modulating cellular tight junction integrity and thereby increasing blood-brain and intestinal barrier permeabilities (1,2). Dietary nutrients, especially polyphenols in fruit and vegetables, can beneficially affect cellular tight junction integrity, modulate the gut microbiome and reduce pro-inflammatory effects (3).

Methods

The effects of blueberries on, 1. circulating tight junction proteins especially relevant for the integrity of the intestinal and blood-brain barriers and, 2. on GI pain and symptoms (Gastrointestinal Clinical Rating Scale: GSRS), life functioning and quality of life (Outcome Questionnaire OQ45.2) and, 3. on stool consistency (Bristol stool scale: BSS) were prospectively examined in DGBI. Successive patients with irritable bowel syndrome or functional dyspepsia received freeze-dried blueberries (equivalent to 180g of fresh blueberries) or sugar and energy-matched placebo for 6 weeks in a double-blind, randomized, cross-over study, with a washout period of 2 to 4 weeks between treatments. Serum concentrations of claudin-3, claudin-5 and zonula occludens-1 (ZO-1) were measured by ELISA and the GSRS, OQ45.2 and BSS scores were collected at baseline and after 6 weeks. The changes in protein concentrations and in GSRS, OQ45.2 and BSS scores from baseline were correlated.

Results

In 43 patients (37 females, mean age±SD 31±12yr) blueberry treatment for 6 weeks improved GSRS and OQ45.2 scores (both p=0.01) and increased claudin-3 serum concentrations (p=0.003). Furthermore, with blueberries increased serum claudin-5 concentrations correlated with improved GSRS and OQ45.2 scores (Spearman’s r= -0.38, p=0.016; r= -0.36, p=0.024, resp.), while increased ZO-1 levels correlated with improved OQ45.2 scores (r= -0.32, p=0.046). With placebo there were neither significant changes in clinical outcomes nor in serum concentration of tight junction proteins, and there were no correlations between these outcomes. The median BSS score was not significantly changed during either treatment, although constipation was relieved more frequently by blueberries.

Conclusions

Blueberries given for 6 weeks decreased pain and symptoms, and improved measures of quality of life and life functioning scores in patients with DGBI. Concomitantly, increased serum concentrations of claudin-3, a tight junction protein important in the regulation of intestinal and other barrier tight junction integrity, were observed. Increases in circulating tight junction protein levels relevant in tightening blood-brain (claudin-5) and other (ZO-1) barrier tight junctions correlated with an improvement in symptoms during blueberry, but not placebo ingestion. Modulation of intestinal and/or blood-brain barrier tight junction integrity by the polyphenol and fibre components of blueberries may constitute a relevant mechanism in improving the clinical outcome of patients with DGBI.

References

(1) Martin CR, Osadchiy V, Kalani A, Mayer EA. Cell Mol Gastroenterol Hepatol. 2018;6:133-148. (2) Hanning N, Edwinson AL, Ceuleers H, et al. Therap Adv Gastroenterol. 2021;14:1756284821993586. (3) Suzuki T. Anim Sci J. 2020;91:e13357.

Presenting Author

Clive Wilder-Smith

Poster Authors

Clive Wilder-Smith

MD

Brain-Gut Research Group

Lead Author

Andrea Materna

Lead Author

Aase Handberg PhD

Lead Author

Søren Olesen MD PhD

Lead Author

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Visceral Pain – Gastrointestinal/Abdominal