Interindividual differences in aronia juice tolerability linked to gut microbiome and metabolome changes—secondary analysis of a randomized placebo-controlled parallel intervention trial

Abstract

Background Aronia melanocarpa is a berry rich in polyphenols known for health benefits. However, the bioavailability of polyphenols has been questioned, and the individual taste acceptance of the fruit with its specific flavor varies. We recently observed substantial differences in the tolerability of aronia juice among healthy females, with half of the individuals tolerating aronia juice without complaints. Given the importance of the gut microbiome in food digestion, we investigated in this secondary analysis of the randomized placebo-controlled parallel intervention study (ClinicalTrials.gov registration: NCT05432362) if aronia juice tolerability was associated with changes in intestinal microbiota and bacterial metabolites, seeking for potential mechanistic insights into the impact on aronia polyphenol tolerance and metabolic outcomes. Results Forty females were enrolled for this 6-week trial, receiving either 100 ml natural aronia juice (verum, V) twice daily or a polyphenol-free placebo (P) with a similar nutritional profile, followed by a 6-week washout. Within V, individuals were categorized into those who tolerated the juice well (Vt) or reported complaints (Vc). The gut microbiome diversity, as analyzed by 16S rRNA gene-based next-generation sequencing, remained unaltered in Vc but changed significantly in Vt. A MICOM-based flux balance analysis revealed pronounced differences in the 40 most predictive metabolites post-intervention. In Vc carbon-dioxide, ammonium and nine O-glycans were predicted due to a shift in microbial composition, while in Vt six bile acids were the most likely microbiota-derived metabolites. NMR metabolomics of plasma confirmed increased lipoprotein subclasses (LDL, VLDL) post-intervention, reverting after wash out. Stool samples maintained a stable metabolic profile. Conclusion In linking aronia polyphenol tolerance to gut microbiota-derived metabolites, our study explores adaptive processes affecting lipoprotein profiles during high polyphenol ingestion in Vt and examines effects on mucosal gut health in response to intolerance to high polyphenol intake in Vc. Our results underpin the importance of individualized hormetic dosing for beneficial polyphenol effects, demonstrate dynamic gut microbiome responses to aronia juice, and emphasize personalized responses in polyphenol interventions. Graphical Abstract

Potential Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports

“…To date, non-steroidal anti-inflammatory agents and diseasemodifying anti-rheumatic drugs, like immunosuppressants and monoclonal antibodies (e.g., rituximab and tocilizumab) combined with methotrexate, have been largely used to attenuate RA; however, most of them are expensive, rarely effective or tolerable, and lead to several unwanted effects, including allergy and infections, gastrointestinal problems, fluid retention, renal dysfunction and systemic vasculitis, cytopenia, lymphopenia, neutropenia, and the elevation of transaminase and cholesterol [7][8][9][10][11][12][13]. Among the new and most promising availability strategies, special attention has been given to bioactive molecules largely found in nature, namely, polyphenols, since their chemical structure with catechol methoxy and pyrogallol groups confer them notable health benefits, like antioxidant, anti-inflammatory, anti-bacterial, and antiproliferative activities, as well as the capacity to prevent neurological and cardiovascular pathologies, promote gastrointestinal health and vision without, it is believed, side-effects, and enhance wound healing [14][15][16][17][18][19][20][21][22][23]. In addition, polyphenols are also easier to obtain, water-soluble, and more economical than chemical drugs, and have already shown effectiveness in inhibiting JAK proteins and JAK/STAT signaling pathways [24][25][26][27][28].…”

The Role of Dietary Phenolic Compounds in the Prevention and Treatment of Rheumatoid Arthritis: Current Reports

“…Until date, non-steroidal anti-inflammatory agents and disease-modifying anti-rheumatic drugs, like immunosuppressants and monoclonal antibodies (e.g., rituximab and tocilizumab) combined with methotrexate, are largely used to attenuate RA; however, most of them are expensive, rarely effective and tolerable and lead to several unwanted effects, including allergy and infections, gastrointestinal problems, fluid retention, renal dysfunction and systemic vasculitis, cytopenia, lymphopenia, neutropenia and the elevation of transaminase and cholesterol [7][8][9][10][11][12][13]. Among the new and most promising availability strategies, special attention has been given to bioactive molecules largely found in nature, namely polyphenolics, since their chemical structure with catechol methoxy and pyrogallol groups, confers them notable health benefits, like antioxidant, anti-inflammatory and antiproliferative activities, as well as capacity to prevent neurological and cardiovascular pathologies, without, it is believed, side-effects [14][15][16][17][18][19][20][21]. In addition, polyphenolics are also easier to obtain, water-soluble and more economical than chemical drugs, and have already shown effectiveness in inhibiting JAK proteins and JAK/STAT signalling pathways [22][23][24][25][26].…”