Introduction
Blueberry ingestion resulted in significant abdominal symptom relief, improved Gastrointestinal Symptom Rating (GSRS) and quality-of-life and life functioning scores by Outcome Questionnaire (OQ 45.2) in patients with DGBI1. It is unclear via which mechanisms blueberries exert their beneficial effect in DGBI2.
Aims & Methods
We explored the associations between symptomatic responses to blueberry ingestion, faecal microbiota composition, clinical phenotypes and tests of disease mechanisms in DGBI.
Male and female patients aged 18-60 years with DGBI (irritable bowel syndrome or functional dyspepsia, Rome 4), were randomised to blueberries (30g freeze-dried powder = 180g fresh blueberries) or placebo daily for 6 weeks in a double-blind, cross-over study. GSRS and OQ-45.2 were assessed before and in week 6 of each treatment period. Responders were defined by improved GSRS or OQ-45.2. Demographics, lifestyle and symptom details were documented at baseline3. Further variables were gathered before and in week 6 of treatment: Bristol Stool Scale, breath H2, CH4 and symptoms after fructose 35g, cognitive tests (CANTAB®), skin fluorescence for advanced glycation end-products and serum tight junction proteins (claudin-3 and -5, zonula occludens-1). Stool microbiome analysis was performed by DNA extraction and sequencing for shotgun metagenomics. Nonmetric multidimensional scaling ordination plots based on Bray-Curtis dissimilarity were generated at the species level with clinical covariates. Spearman association of microbial species with demographics, clinical phenotype and mechanistic tests at baseline and during treatment were analysed by stratifying data into pre- and post-treatment groups, as well as responders and non-responders by GSRS and OQ-45.2.
Results
In 43 DGBI patients there were significant associations between faecal microbiota composition, clinical phenotypes and tests relating to disease mechanisms that were distinct between blueberry responders and non-responders. Examples of prominent baseline associations were breath gases after fructose with Ruminococcus sp AF41_9 in GSRS responders and with Eggerthella lenta, Lachnospiraceae bacterium AM48_27BH, Phocaeicola vulgatus, Ruminococcus callidus, Mediterraneibacter glycyrrhiznilyticus in non-responders. Cognitive skills were associated with Clostridium sp AF34_13 and Clostridiaceae bacterium Marseille_Q4149 in responders, and with Blautia glucerasea, Eggerthella lenta and Ruminococcus callidus in non-responders. Tight junction protein levels correlated with Clostridiaceae bacterium Marseille_Q4149, Anaerobutyricum hallii and Bacteroides intestinalis in responders and with Anaerostipes hadrus, Blautia faecicola, Blautia glucerasea, Clostridia bacterium UC5_1_1D1 and Ruminococcus gnavus in non-responders. During blueberry ingestion new associations between bacterial taxa and GSRS, breath gases after fructose, tight junction protein levels emerged, which were largely distinct between responder groups. Responders by OQ-45.2 showed associations between bacterial taxa, demographics and mechanistic tests both at baseline and during blueberry dosing that were largely distinct from those of GSRS responders.
Conclusion
In patients with DGBI, GI and general symptom relief with blueberry ingestion were characterised by specific, distinct associations between faecal microbiota, clinical phenotype and tests of disease mechanisms at baseline and during treatment. This first longitudinal blueberry treatment study in DGBI patients suggests an important role of the intestinal microbiota in symptom genesis warranting further study.
References
1Wilder-Smith CH, Materna A, Olesen SS. Blueberries Improve Abdominal Symptoms, Well-Being and Functioning in Patients with Functional Gastrointestinal Disorders. Nutrients. 2023 May 20;15(10):2396.
2Kalt W, Cassidy A, Howard LR, Krikorian R, Stull AJ, Tremblay F, Zamora-Ros R. Recent Research on the Health Benefits of Blueberries and Their Anthocyanins. Adv Nutr. 2020 Mar 1;11(2):224-236.
3Wilder-Smith CH, Drewes AM, Materna A, Olesen SS. Extragastrointestinal Symptoms and Sensory Responses During Breath Tests Distinguish Patients With Functional Gastrointestinal Disorders. Clin Transl Gastroenterol. 2020 Aug;11(8):e00192.
Disclosure
This study was supported by a research grant from the US Highbush Blueberry Council.
