PROVIT-CLOCK: A Potential Influence of Probiotics and Vitamin B7 Add-On Treatment and Metabolites on Clock Gene Expression in Major Depression.

INTRODUCTION: An increasing body of evidence suggests a strong relationship between gut health and mental state. Lately, a connection between butyrate-producing bacteria and sleep quality has been discussed. The PROVIT study, as a randomized, double-blind, 4-week, multispecies probiotic intervention study, aims at elucidating the potential interconnection between the gut's metabolome and the molecular clock in individuals with major depressive disorder (MDD). METHODS: The aim of the PROVIT-CLOCK study was to analyze changes in core clock gene expression during treatment with probiotic intervention versus placebo in fasting blood and the connection with the serum- and stool-metabolome in patients with MDD (n = 53). In addition to clinical assessments in the PROVIT study, metabolomics analyses with 1H nuclear magnetic resonance spectroscopy (stool and serum) and gene expression (RT-qPCR) analysis of the core clock genes ARNTL, PER3, CLOCK, TIMELESS, NR1D1 in peripheral blood mononuclear cells of fasting blood were performed. RESULTS: The gene expression levels of the clock gene CLOCK were significantly altered only in individuals receiving probiotic add-on treatment. TIMELESS and ARNTL gene expression changed significantly over the 4-week intervention period in both groups. Various positive and negative correlations between metabolites in serum/stool and core clock gene expression levels were observed. CONCLUSION: Changing the gut microbiome by probiotic treatment potentially influences CLOCK gene expression. The preliminary results of the PROVIT-CLOCK study indicate a possible interconnection between the gut microbiome and circadian rhythm potentially orchestrated by metabolites.

Impaired implicit learning in adults with anorexia nervosa.

OBJECTIVE: Cognitive alterations play an important role in the pathophysiology and treatment of anorexia nervosa (AN). Previous studies suggest that some implicit learning processes may be inhibited in AN. However, this has not yet been fully explored. The purpose of this study is to analyze implicit learning in patients with AN in comparison to healthy controls. METHODS: In this pilot-study, a total of 21 patients diagnosed with AN and 21 matched controls were administered the weather prediction task (WPT), a probabilistic implicit category learning task that consists of two sub-variants. During the feedback (FB) version of the task, participants learn associations between tarot cards and weather outcomes via an operant learning model through which they receive immediate FB on their answers, whereas during the paired associate (PA) variant, participants are directly asked to memorize given associations. RESULTS: AN patients showed selective impairment on the FB task where they scored significantly lower both in comparison to controls (p = .001) who completed the same task and when compared to their own performance on the PA variant (p = .006). Clinical measures showed no significant correlations with test scores. DISCUSSION: Our results demonstrate implicit FB learning deficiencies in adult patients with AN. These impairments may have an impact on the effect of psychotherapeutic interventions and could partially explain the lack of treatment response in AN. Further studies are necessary to derive when and through which mechanisms these alterations originate, and to what extent they should be considered during treatment of the disorder. PUBLIC SIGNIFICANCE: Cognitive impairments pose a challenge in the management of anorexia nervosa. Improved comprehension of cognitive alterations could lead to a greater understanding of the disease and adaptation of psychotherapeutic treatments. In this study, we found that implicit feedback learning in anorexia nervosa is impaired compared to healthy controls. This could indicate the necessity of treatment adaptations in the form of therapy tools without feedback and a larger focus on psychoeducation.

An encapsulated fruit, vegetable and berry juice powder concentrate increases plasma values of specific carotenoids and vitamins.

Vitamins and carotenoids are organic compounds that are important for vital functions of the human organism. Since the human body is not able to synthesize most of these micronutrients, they need to be supplied by the intake of food or supplements. The aim of this study was to analyze whether a whole food based, encapsulated fruit, berry, and vegetable juice powder concentrate provides bioavailable carotenoids and vitamins A (all-trans retinol), E and C. Eighteen healthy subjects received 6 capsules a day for 8 weeks, which provided 2.91 mg ß-carotene, 490 µg vitamin A, 18.7 mg vitamin E, 159 mg vitamin C, 6.1 mg lutein and 1 mg lycopene. Plasma concentrations of several carotenoids and vitamins before and after supplementation were measured. After 8 weeks of supplementation, the plasma concentration of the following carotenoids increased significantly: α-carotene increased from 59.6 ± 22.4 nmol/L to 85.7 ± 24.2 nmol/L (p = 0.002), ß-cryptoxanthin from 106.7 ± 39.8 nmol/L to 151.9 ± 57.9 nmol/L (p = 0.017), and lycopene from 1.2 ± 0.5 µmol/L to 1.7 ± 0.5 µmol/L (p = 0.005). Significant increases were also observed for plasma concentrations of vitamin C from 70 ± 20 µmol/L to 90 ± 10 µmol/L (p < 0.001), all-trans retinol from 1.99 ± 0.24 µmol/L to 2.30 ± 0.66 µmol/L (p = 0.015), and α-tocopherol from 27 ± 6 µmol/L to 32 ± 6 µmol/L (p = 0.008). For those micronutrients with accepted plasma reference ranges, all observed increases levelled off around the upper limit of the individual reference range. The data demonstrate that the investigated supplement is able to increase plasma concentrations of certain carotenoids and vitamins of healthy subjects within 8 weeks.

Effects of a plant-based fatty acid supplement and a powdered fruit, vegetable and berry juice concentrate on omega-3-indices and serum micronutrient concentrations in healthy subjects.

The major aim of this controlled, randomised, open-labelled, parallel-grouped, clinical trial was to investigate whether supplementation with different dosages of omega-3 fatty acids (0.5 g/d and 1 g/d) from a plant-based fatty acid supplement affected omega-3-indices (O3I) in well-nourished, healthy people. In addition, the combined ingestion of the plant-based fatty acid supplement, together with an encapsulated fruit, vegetable and berry (FVB) juice powder concentrate, was applied in order to observe the absorption of certain micronutrients and to examine some aspects related to the safe consumption of the products. The data demonstrate that the intake of only 0.5 g/day of omega-3 fatty acids from of a vegan supplement was able to increase the O3I significantly after 8 and 16 weeks. The combined ingestion with the FVB supplement concurrently increased serum concentrations of specific vitamins and carotenoids without effects on hepatic, kidney and thyroid function or changes in blood lipids.

[Pilot study: Gut microbiome and intestinal barrier in anorexia nervosa]. / Pilotstudie: Mikrobiom und Darmbarriere bei Anorexia nervosa.

INTRODUCTION: Recent research has shown changes of the intestinal flora in anorexia nervosa (AN) patients. Alpha diversity (AD) represents the number of different bacterial species in the gut. Reduced AD and a leaky gut (zonulin) lead to inflammation and changes in nutrient absorption. METHODS: AD was calculated from stool samples of 18 AN patients and 20 normal weight controls (NC) after 16S ribosomal RNA sequencing. Furthermore, Zonulin as an indicator of gut barrier function and inflammation parameters were investigated. RESULTS: AN patients had significantly lower AD compared to NC (number of observed species p=0.042, Chao1 Diversity Index p=0.043). Zonulin was not significantly altered in AN patients compared to NC. There were no significant correlations of serum parameters and AD. DISCUSSION: Regardless of gut permeability, AN patients showed significantly decreased AD compared to NC. Decreased AD can have an additional negative impact on calorie intake in AN. These results contribute to a better understanding of the illness and the development of new therapeutic options.

Non-celiac gluten sensitivity: people without celiac disease avoiding gluten-is it due to histamine intolerance?

INTRODUCTION: Food intolerance/malabsorption is caused by food ingredients, carbohydrates (mainly lactose and fructose), proteins (gluten), and biogenic amines (histamine) which cause nonspecific gastrointestinal and extra-intestinal symptoms. Here we focus on possible etiologic factors of intolerance/malabsorption especially in people with non-celiac gluten sensitivity (NCGS) or the so-called people without celiac disease avoiding gluten (PWCDAG) and histamine intolerance. METHODS: Recognizing the recently described symptoms of NCGS (PWCDAG) we review correlations and parallels to histamine intolerance (HIT). RESULTS: We show that intestinal and extra-intestinal NCGS (PWCDAG) symptoms are very similar to those which can be found in histamine intolerance. CONCLUSIONS: After a detailed diagnostic workup for all possible etiologic factors in every patient, a targeted dietary intervention for single or possibly combined intolerance/malabsorption might be more effective than a short-term diet low in fermentable oligo-, di- and monosaccharides and polyols (FODMAP) or the untargeted uncritical use of gluten-free diets.

The Role of Nutrition and the Gut-Brain Axis in Psychiatry: A Review of the Literature.

INTRODUCTION: Individuals suffering from psychiatric disorders experience high levels of illness burden and a significantly reduced quality of life. Despite targeted psychopharmacological strategies and complementary psychotherapeutic procedures only moderate effects are obtained, and the risk of relapse is high in many patients. Worldwide, psychiatric diseases such as depression are continuously increasing, challenging the personal life of the affected as well as their families, but also whole societies by increasing disability, early retirement and hospitalization. According to current scientific knowledge psychiatric disorders are caused by a multifactorial pathogenesis, including genetics, inflammation and neurotransmitter imbalance; furthermore, also lifestyle-associated factors gain rising importance. In line with this, there is growing evidence that the gut microbiota and nutrition have an impact on the onset and course of psychiatric disorders. AIM: This narrative review highlights the important role of nutrition in psychiatric care and underlines the significance of nutritional advice in the multifactorial, biopsychosocial treatment of patients. It focuses on current dietary interventions such as the Mediterranean diet, dietary supplements and modifications of the gut microbiota with pre-, pro- and postbiotics. RESULTS: Recent studies support the connection between the quality of diet, gut microbiota and mental health through regulation of metabolic functions, anti-inflammatory and antiapoptotic properties and the support of neurogenesis. Dietary coaching to improve mental health seems to be an additional, cost-effective, practical, nonpharmacological intervention for individuals with psychiatric disorders. CONCLUSION: The use of nutritional interventions in psychiatry equips therapists with a promising tool for both the prevention and treatment of psychiatric disorders. Besides pharmacological therapy, psychotherapy and physical activity, nutritional interventions are an important pillar in the multifactorial, biopsychosocial treatment of psychiatric disease and could be used as a potential therapeutic target.

Gut microbiota and body composition in anorexia nervosa inpatients in comparison to athletes, overweight, obese, and normal weight controls.

OBJECTIVES: Anorexia nervosa (AN) is a heterogeneous eating disorder associated with alterations of body structure and the gut microbiome. We aimed to investigate the gut microbiota composition of a large female cohort including different BMI groups and activity levels along with body composition parameters. METHOD: 106 female participants were included in this cross-sectional study: AN patients (n = 18), athletes (n = 20), normal weight (n = 26), overweight (n = 22), and obese women (n = 20). DNA was extracted from stool samples and subjected to 16S rRNA gene analysis. The software Quantitative Insights Into Microbial Ecology (QIIME) was used to analyze data. Additionally, we performed anthropometric assessments, ultrasound measurements of subcutaneous adipose tissue thickness, bioimpedance analysis, administered depression inventories, and ascertained laboratory parameters and dietary intakes. RESULTS: Alpha diversity was particularly lower in AN patients and obese participants compared to other groups, while athletes showed highest alpha diversity. Several categories significantly associated with community structure were identified: body fat parameters, serum lipids, CRP, depression scales and smoking. Comparative analysis revealed Coriobacteriaceae as the only enriched phylotype in AN compared to other entities (LDA score >3.5). DISCUSSION: This study provides further evidence of intestinal dysbiosis in AN and sheds light on characteristics of the gut microbiome in different BMI and physical activity groups. These insights point to new modulation possibilities of the gut microbiota which could improve the standard therapy of AN.

Reduced olfactory performance is associated with changed microbial diversity, oralization, and accumulation of dead biomaterial in the nasal olfactory area.

The partial or complete loss of the sense of smell, which affects about 20% of the population, impairs the quality of life in many ways. Dysosmia and anosmia are mainly caused by aging, trauma, infections, or even neurodegenerative disease. Recently, the olfactory area-a site containing the olfactory receptor cells responsible for odor perception-was shown to harbor a complex microbiome that reflects the state of olfactory function. This initially observed correlation between microbiome composition and olfactory performance needed to be confirmed using a larger study cohort and additional analyses. A total of 120 participants (middle-aged, no neurodegenerative disease) were enrolled in the study to further analyze the microbial role in human olfactory function. Olfactory performance was assessed using the Sniffin' Stick battery, and participants were grouped accordingly (normosmia: n = 93, dysosmia: n = 27). The olfactory microbiome was analyzed by 16S rRNA gene amplicon sequencing and supplemented by metatranscriptomics in a subset (Nose 2.0). Propidium monoazide (PMA) treatment was performed to distinguish between intact and non-intact microbiome components. The gastrointestinal microbiome of these participants was also characterized by amplicon sequencing and metabolomics and then correlated with food intake. Our results confirm that normosmics and dysosmics indeed possess a distinguishable olfactory microbiome. Alpha diversity (i.e., richness) was significantly increased in dysosmics, reflected by an increase in the number of specific taxa (e.g., Rickettsia, Spiroplasma, and Brachybacterium). Lower olfactory performance was associated with microbial signatures from the oral cavity and periodontitis (Fusobacterium, Porphyromonas, and Selenomonas). However, PMA treatment revealed a higher accumulation of dead microbial material in dysosmic subjects. The gastrointestinal microbiome partially overlapped with the nasal microbiome but did not show substantial variation with respect to olfactory performance, although the diet of dysosmic individuals was shifted toward a higher meat intake. Dysosmia is associated with a higher burden of dead microbial material in the olfactory area, indicating an impaired clearance mechanism. As the microbial community of dysosmics (hyposmics and anosmics) appears to be influenced by the oral microbiome, further studies should investigate the microbial oral-nasal interplay in individuals with partial or complete olfactory loss.IMPORTANCEThe loss of the sense of smell is an incisive event that is becoming increasingly common in today's world due to infections such as COVID-19. Although this loss usually recovers a few weeks after infection, in some cases, it becomes permanent-why is yet to be answered. Since this condition often represents a psychological burden in the long term, there is a need for therapeutic approaches. However, treatment options are limited or even not existing. Understanding the role of the microbiome in the impairment of olfaction may enable the prediction of olfactory disorders and/or could serve as a possible target for therapeutic interventions.

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.

Advances in the gut microbiome and mood disorders.

PURPOSE OF REVIEW: The gut microbiome is in constant bidirectional communication with the brain through the microbiota-gut-brain-axis. Mood disorders are among the most common psychiatric disorders and include major depressive disorder and bipolar disorder. The gut microbiome is altered in individuals with mood disorders and has a role in its inflammatory pathophysiology. In this article, we performed a narrative review of clinical studies, randomized controlled trials and meta-analyses addressing advances in gut microbiome research in mood disorders and included articles that were published between 2021 and 2022. RECENT FINDINGS: Studies highlight transdiagnostic alterations of microbiota in mood disorders, with reductions of butyrate-producing bacteria. Participants with major depressive disorder showed altered beta-diversity, while participants with bipolar disorder showed reduced alpha-diversity. Both disorders exhibit alterations in the metabolome. Early pilot studies addressed the possibility of using the gut microbiome for the prediction of treatment response and the blood microbiome for the diagnosis of psychiatric disorders. Findings from clinical trials support the use of probiotics as an add-on therapy for major depressive disorder. The second published case report in the literature reported a favourable outcome of a patient with bipolar disorder after faecal microbiota transplantation. SUMMARY: Gut microbiome modulations allow new treatment strategies including the use of psychobiotics for the treatment and prevention of mood disorders. Well designed clinical trials aiming for personalized medicine are needed to investigate the efficacy and safety of psychobiotic interventions.

Serum Diamine Oxidase Values, Indicating Histamine Intolerance, Influence Lactose Tolerance Breath Test Results.

Lactose intolerance (LIT) is one of the major causes of irritable bowel syndrome (IBS) spectrum complaints. Differences in inadequate lactose digestion are described as various LIT phenotypes with basically unknown pathophysiology. In LIT patients, we retrospectively assessed the effect of histamine intolerance (HIT) on expiratory hydrogen (H2) during H2 lactose breath tests. In a retrospective evaluation of charts from 402 LIT patients, 200 patients were identified as having only LIT. The other 202 LIT patients were found to additionally have diamine oxidase (DAO) values of <10 U/mL, which indicates histamine intolerance (HIT). To identify HIT, standardized questionnaires, low serum DAO values and responses to a histamine-reduced diet were used. Patients were separated into three diagnostic groups according to the result of H2 breath tests: (1) LIT, with an H2 increase of >20 parts per million (ppm), but a blood glucose (BG) increase of >20 mg/dL, (2) LIT with an H2 increase of 20 ppm in combination with a BG increase of <20 mg/dL, and (3) LIT with an exhaled H2 increase of <20 ppm and BG increase of <20 mg/dL. Pairwise comparison with the Kruskal Wallis test was used to compare the areas under the curve (AUC) of LIT and LIT with HIT patients. Exhaled H2 values were significantly higher in H2 > 20 ppm and BG < 20 mg/dL patients with LIT and HIT (p = 0.007). This diagnostic group also showed a significant higher number of patients (p = 0.012) and a significant higher number of patients with gastrointestinal (GI) symptoms during H2 breath tests (p < 0.001). Therefore, low serum DAO values, indicating HIT, influence results of lactose tolerance breath tests.

Anorexia Nervosa Is Associated with a Shift to Pro-Atherogenic Low-Density Lipoprotein Subclasses.

Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5−24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors.

Helicobacter pylori infection and lactose intolerance increase expiratory hydrogen.

Infection with Helicobacter pylori (H.pylori) may cause dyspepsia and/or unexplained functional nonspecific, gastrointestinal complaints of the irritable bowel syndrome (IBS) spectrum. Hitherto, in H. pylori infected patients with symptoms of the IBS spectrum the occurrence of additional food intolerance/malabsorption is not evaluated. We used a retrospective analysis of charts from 548 patients who presented with gastrointestinal complaints of the irritable bowel syndrome spectrum. An enzyme-linked IgA immunosorbent assay or histologic evaluation of gastric mucosa were used to detect H. pylori infection. A hydrogen breath (H2) test was performed to evaluate fructose malabsorption (FM) and lactose intolerance (LIT). Serum diamine oxidase value of <10 U/ml and a response to a histamine-reduced diet was used to identify histamine intolerance (HIT). We found 293 patients infected with H. pylori, within these were 58 H. pylori patients with LIT, 23 H. pylori LIT patients with FM and 46 H. pylori LIT patients with HIT. Additionally, 13 H. pylori, lactose- and histamine intolerance patients also had FM. The Kruskal Wallis test and pairwise comparison were used to analyze differences of the area under the curve of expiratory hydrogen. In lactose H2 breath tests compared with LIT-only patients, LIT with H. pylori, LIT and H. pylori with HIT, LIT and H. pylori with FM showed significantly higher exhaled H2 levels (p=0.022). Pairwise comparison demonstrated H. pylori infected patients with LIT exhaled more H2 compared to LIT-only (p=0.029). H. pylori with lactose- and histamine intolerance, and H. pylori with lactose-, histamine intolerance and FM compared to H. pylori-only patients indicated a significantly higher occurrence of stomach pain during lactose H2 breath tests (p=0.012 and p=0.005, respectively). We demonstrate that LIT patients with high expiratory H2 levels in lactose breath tests may have H. pylori infection and possibly additional food intolerance/malabsorption. Subsequently, besides H. pylori eradication, a dietician is necessary for an individually tailored reduction- or exclusion diet of symptom triggering food components.

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.

Cardiac vagal activity is associated with gut-microbiome patterns in women-An exploratory pilot study.

Introduction: A functional reciprocity between the gut microbiome and vagal nerve activity has been suggested, however, human studies addressing this phenomenon are limited. Methods: Twenty-four-hour cardiac vagal activity (CVA) was assessed from 73 female participants (aged 24.5 ± 4.3 years). Additionally, stool samples were subjected to 16SrRNA gene analysis (V1-V2). Quantitative Insights Into Microbial Ecology (QIIME) was used to analyse microbiome data. Additionally, inflammatory parameters (such as CRP and IL-6) were derived from serum samples. Results: Daytime CVA correlated significantly with gut microbiota diversity (r sp = 0.254, p = 0.030), CRP (r sp = -0.348, p = 0.003), and IL-6 (r sp = -0.320, p = 0.006). When the group was divided at the median of 24 h CVA (Mdn = 1.322), the following features were more abundant in the high CVA group: Clostridia (Linear discriminant analysis effect size (LDA) = 4.195, p = 0.029), Clostridiales (LDA = 4.195, p = 0.029), Lachnospira (LDA = 3.489, p = 0.004), Ruminococcaceae (LDA = 4.073, p = 0.010), Faecalibacterium (LDA = 3.982, p = 0.042), Lactobacillales (LDA = 3.317, p = 0.029), Bacilli (LDA = 3.294, p = 0.0350), Streptococcaceae (LDA = 3.353, p = 0.006), Streptococcus (LDA = 3.332, p = 0.011). Based on Dirichlet multinomial mixtures two enterotypes could be detected, which differed significantly in CVA, age, BMI, CRP, IL-6, and diversity. Conclusions: As an indicator of gut-brain communication, gut microbiome analysis could be extended by measurements of CVA to enhance our understanding of signalling via microbiota-gut-brain-axis and its alterations through psychobiotics.

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.

Hypercarotenemia in Anorexia Nervosa Patients May Influence Weight Balance: Results of a Clinical Cross-Sectional Cohort Study.

Introduction: Anorexia nervosa (AN) can co-occur with hypercarotenemia, a clinical condition characterized by elevated ß-carotene in plasma and skin tissue. Carotenoids have known anti-obesogenic effects in adipocyte biology. Thus, carotenoids may potentially play a retarding role in weight gain during the recovery of AN patients. This study evaluated the plasma carotenoid profile and subcutaneous adipose tissue (SAT) in a cohort of AN patients and normal weight (NW) controls. Methods: Plasma concentrations of α-carotene, ß-carotene, ß-cryptoxanthin, and lycopene were determined by HPLC analysis. SAT thicknesses were measured by a highly accurate and reliable ultrasound technique. Information on dietary intakes were collected by repeated 24-h recalls. Results: Sixty-two females (AN: n = 18, NW: n = 44) were included. The concentrations of ß-cryptoxanthin (p = 0.045) and lycopene (p = 0.004) were significantly lower in AN patients. ß-carotene levels were higher in AN patients (n.s.) and α-carotene did not differ significantly. SAT thickness was significantly lower in AN patients compared to controls (p < 0.001). ß-carotene was significantly negative (r s = -0.471) and lycopene significantly positive (r s = 0.366) correlated with SAT. The correlation of ß-carotene and SAT was even higher in the AN group alone (r s = -0.742). Also, ß- cryptoxanthin and the sum of provitamin A carotenoids were correlated to SAT (r s = -0.647 and r s = -0.746, respectively) in AN patients. Fruits and vegetable intake did not differ significantly between AN and NW but adjusted for SAT, AN patients consumed relatively higher amounts (p = 0.006). Conclusion: Higher plasma ß-carotene concentrations were associated with reduced SAT levels, most probably due to a reduced ability of the remaining adipose tissue to store carotenoids. Thus, the antiobesity effects of carotenoids might impact the treatment success of undernutrition and AN. A systemic carotenoid overload may contribute to changes in adipogenesis and metabolic capacities for energy storage. Therefore, high plasma ß-carotene may be a marker of delay in weight recovery in AN patients. Interventional studies should consider including carotenoid-status in AN treatment.

Obesity Affects HDL Metabolism, Composition and Subclass Distribution.

BACKGROUND: Obesity increases the risk of coronary heart disease, partly due to its strong association with atherogenic dyslipidemia, characterized by high triglycerides and low high-density lipoprotein (HDL) cholesterol levels. Functional impairment of HDL may contribute to the increased cardiovascular mortality, but the effect of obesity on composition, structure, and function of HDL is not well understood. Design and Methods: We determined HDL composition, HDL subclass distribution, parameters of HDL function, and activities of most important enzymes involved in lipoprotein remodeling, including lecithin-cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP) in relatively young normal weight (n = 26), overweight (n = 22), and obese (n = 20) women. RESULTS: Obesity (body mass index (BMI) ≥ 30) was associated with noticeable changes in LCAT and CETP activities and altered HDL composition, such as decreased apolipoprotein A-I, cholesterol, and phospholipid content, while pro-inflammatory HDL serum amyloid a content was increased. We observed a marked shift towards smaller HDL subclasses in obesity linked to lower anti-oxidative capacity of serum. LCAT activity, HDL subclass distribution, and HDL-cholesterol were associated with soluble leptin receptor, adiponectin, and liver enzyme activities. Of note, most of these alterations were only seen in obese women but not in overweight women. CONCLUSIONS: Obesity markedly affects HDL metabolism, composition, and subclass distribution linked to changes in liver and adipose tissue. HDL dysfunction may contribute to increased cardiovascular risk in obesity.