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

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.

Immunomodulatory Effects of Aronia Juice Polyphenols-Results of a Randomized Placebo-Controlled Human Intervention Study and Cell Culture Experiments.

Dietary polyphenols, which are present in Aronia melanocarpa, have been associated with various beneficial effects on human health including antioxidant, antiviral, and anti-inflammatory activities. We aimed to investigate the immunomodulatory effects of aronia juice polyphenols in a randomized placebo-controlled human intervention study and cell culture experiments. A total of 40 females were asked to consume either 200 mL of aronia juice or a placebo drink for six weeks and were investigated again after a washout period of another six weeks. We observed that only half of the participants tolerated the aronia juice well (Vt) and the other half reported complaints (Vc). The placebo (P) was generally tolerated with one exception (p = 0.003). Plasma polyphenol levels increased significantly in Vt after the intervention (p = 0.024) but did neither in P nor in Vc. Regulatory T cell (Treg) frequencies remained constant in Vt and P during the intervention, whereas Tregs decreased in Vc (p = 0.018). In cell culture, inhibiting effects of ferulic acid (p = 0.0005) and catechin (p = 0.0393) on the differentiation of Tregs were observed as well as reduced activation of CD4-T cells in ferulic acid (p = 0.0072) and aronia juice (p = 0.0163) treated cells. Interestingly, a CD4+CD25-FoxP3+ cell population emerged in vitro in response to aronia juice, but not when testing individual polyphenols. In conclusion, our data strengthen possible individual hormetic effects, the importance of the food matrix for bioactivity, and the need for further investigations on possible impacts of specific physiological features such as the gut microbiota in the context of personalized nutrition.

Oxidative Status in Adult Anorexia Nervosa Patients and Healthy Controls-Results from a Cross-Sectional Pilot Study.

Oxidative stress describes an imbalance of reactive oxygen species (ROS) and antioxidative defence systems. Recently, the consequences of oxidative stress have become a central field of research and have been linked to the genesis of multiple psychiatric diseases. Some oxidative stress parameters have not been investigated before in anorexia nervosa (AN) patients, including the gut microbiota-derived metabolite trimethylamine N-oxide (TMAO) and polyphenols (PPm). In this cross-sectional pilot study, we evaluated these markers together with total peroxides (TOC), antioxidative capacity (TAC), endogenous peroxidase activity (EPA) and antibodies against oxidized LDL (oLAb) in serum samples of 20 patients with AN compared to 20 healthy controls. The antioxidative capacity was significantly decreased in AN patients, with a mean TAC of 1.57 mmol/L (SD: ±0.62); t (34) = -2.181, p = 0.036) compared to HC (mean = 1.91 mmol/L (SD: ±0.56), while the other investigated parameters were not significantly different between the two groups. In AN patients, TAC correlated with EPA (rsp = -0.630, p = 0.009). This study suggests that there is an antioxidative deficiency in AN patients. In this respect, there is a demand for interventional studies to determine whether antioxidants can be used as add-on therapy in the treatment of AN.

Interleukin-6 Gene Expression Changes after a 4-Week Intake of a Multispecies Probiotic in Major Depressive Disorder-Preliminary Results of the PROVIT Study.

Major depressive disorder (MDD) is a prevalent disease, in which one third of sufferers do not respond to antidepressants. Probiotics have the potential to be well-tolerated and cost-efficient treatment options. However, the molecular pathways of their effects are not fully elucidated yet. Based on previous literature, we assume that probiotics can positively influence inflammatory mechanisms. We aimed at analyzing the effects of probiotics on gene expression of inflammation genes as part of the randomized, placebo-controlled, multispecies probiotics PROVIT study in Graz, Austria. Fasting blood of 61 inpatients with MDD was collected before and after four weeks of probiotic intake or placebo. We analyzed the effects on gene expression of tumor necrosis factor (TNF), nuclear factor kappa B subunit 1 (NFKB1) and interleukin-6 (IL-6). In IL-6 we found no significant main effects for group (F(1,44) = 1.33, p = ns) nor time (F(1,44) = 0.00, p = ns), but interaction was significant (F(1,44) = 5.67, p < 0.05). The intervention group showed decreasing IL-6 gene expression levels while the placebo group showed increasing gene expression levels of IL-6. Probiotics could be a useful additional treatment in MDD, due to their anti-inflammatory effects. Results of the current study are promising, but further studies are required to investigate the beneficial effects of probiotic interventions in depressed individuals.

Body modification in Germany: prevalence, gender differences and attitude towards cosmetic surgery.

BACKGROUND: The most popular body modifications are tattoos and piercings and their prevalence has increased in recent years. The current study gathered statistics regarding tattoing, piercing and body-hair removal, differentiated by gender and attitude towards cosmetic surgery. METHODS: The study was based on 2512 individuals and was performed as a population-based survey with the assistance of a demographic consulting company. In addition to sociodemographic questions, specific issues concerning body modification were asked. RESULTS: Men get tattoos more frequently while women more often choose piercings and body hair removal. Women are catching up in the tattoo department and one can no longer observe age differentiations among the younger age groups. Instead there is a decrease in piercings among men. Body hair removal is widespread above all women. People with body modifications tend to be more open-minded about cosmetic surgery. CONCLUSIONS: Tattoos and piercings continue to be the most popular body modification among young adults. The number engaged in tattooing is rising while piercings are still popular among women. Individuals being engaged in body modification are prone to consider cosmetic surgery procedures.

Influence of patient-related and surgery-related risk factors on cognitive performance, emotional state, and convalescence after cardiac surgery.

BACKGROUND: Cardiac surgery may account for complications such as cognitive impairment, depression, and delay of convalescence. This study investigated the influence of different risk factors on cognitive performance, emotional state, and convalescence. METHODS: We included 83 patients undergoing cardiac surgery who had no indication of postoperative delirium. Psychometric testing was performed 1 day before and 7 days after surgery. Neuron-specific enolase (NSE) levels were measured 1 day before and 36 h after surgery. RESULTS: Depression score increased after surgery, but patients showed no clinically significant depression. Postoperative cognitive performance correlated with postoperative depression level and preoperative cognitive performance. Forty-three percent of patients showed postoperative decline. Older patients exhibited a higher postoperative increase in NSE concentrations. Patients undergoing coronary artery bypass grafts or combined procedures exhibited more medical risk factors than those undergoing valve surgery alone. The number of bypass grafts was associated with time of hospitalization, and the number of patient-related risk factors correlated with stay in intensive care unit. CONCLUSIONS: For elderly patients undergoing cardiac surgery, older age, total preexisting medical risk factors, and surgery duration seem to be the most important factors influencing cognitive outcome and convalescence. Results show that, also for patients without postoperative delirium, medical risk factors and intraoperative parameters can result in delay of convalescence.

Evaluation of conditions associated with glycated hemoglobin values below the reference range.

BACKGROUND: Evaluation of conditions associated with glycated hemoglobin (HbA1c) values below the reference range in HbA1c determinations. METHODS: Over a time period of 5 years, HbA1c results were determined with the ion-exchange high-performance liquid chromatography (HPLC) method HA-8140 Menarini. RESULTS: Of approximately 20 000 HbA1c results analyzed, 9 were below the reference range. The reason for HbA1c values below the reference range was found to be liver cirrhosis in 6 patients, anemia with hematological neoplasms in 2 patients, and elevated fetal hemoglobin > 1.5% in one patient. The silent hemoglobin (Hb) variant Hb Graz in 6 patients, Hb Sherwood Forest in 1 patient, homozygote HbS in one patient, and gross hypertriglyceridemia in one patient demonstrated no HbA1c result. CONCLUSIONS: In patients with liver cirrhosis, HbA1c measurements should be used with caution when evaluating long-term glucose control, and samples with suspected Hb variants should be analyzed by hemoglobin electrophoresis. Our study underscores the need for clinical laboratories and physicians to be aware of the limitations of their HbA1c assay methods as well as of the importance of visual inspection of ion-exchange chromatograms to detect HbA1c values below the reference range and abnormalities caused by the interference factors described here.