A mixture of Nordic berries improves cognitive function, metabolic function and alters the gut microbiota in C57Bl/6J male mice.

Our diets greatly influence our health. Multiple lines of research highlight the beneficial properties of eating berries and fruits. In this study, a berry mixture of Nordic berries previously identified as having the potential to improve memory was supplemented to young C57Bl/6J male mice to investigate effects on cognition function, metabolic health, markers of neuroinflammation, and gut microbiota composition. C57Bl/6J male mice at the age of 8 weeks were given standard chow, a high-fat diet (HF, 60%E fat), or a high-fat diet supplemented with freeze-dried powder (20% dwb) of a mixture of Nordic berries and red grape juice (HF + Berry) for 18 weeks (n = 12 animals/diet group). The results show that supplementation with the berry mixture may have beneficial effects on spatial memory, as seen by enhanced performance in the T-maze and Barnes maze compared to the mice receiving the high-fat diet without berries. Additionally, berry intake may aid in counteracting high-fat diet induced weight gain and could influence neuroinflammatory status as suggested by the increased levels of the inflammation modifying IL-10 cytokine in hippocampal extracts from berry supplemented mice. Furthermore, the 4.5-month feeding with diet containing berries resulted in significant changes in cecal microbiota composition. Analysis of cecal bacterial 16S rRNA revealed that the chow group had significantly higher microbial diversity, as measured by the Shannon diversity index and total operational taxonomic unit richness, than the HF group. The HF diet supplemented with berries resulted in a strong trend of higher total OTU richness and significantly increased the relative abundance of Akkermansia muciniphila, which has been linked to protective effects on cognitive decline. In conclusion, the results of this study suggest that intake of a Nordic berry mixture is a valuable strategy for maintaining and improving cognitive function, to be further evaluated in clinical trials.

Identification of Nordic Berries with Beneficial Effects on Cognitive Outcomes and Gut Microbiota in High-Fat-Fed Middle-Aged C57BL/6J Mice.

High-fat diets are associated with neuronal and memory dysfunction. Berries may be useful in improving age-related memory deficits in humans, as well as in mice receiving high-fat diets. Emerging research has also demonstrated that brain health and cognitive function may be related to the dynamic changes in the gut microbiota. In this study, the impact of Nordic berries on the brain and the gut microbiota was investigated in middle-aged C57BL/6J mice. The mice were fed high-fat diets (60%E fat) supplemented with freeze-dried powder (6% dwb) of bilberry, lingonberry, cloudberry, blueberry, blackcurrant, and sea buckthorn for 4 months. The results suggest that supplementation with bilberry, blackcurrant, blueberry, lingonberry, and (to some extent) cloudberry has beneficial effects on spatial cognition, as seen by the enhanced performance following the T-maze alternation test, as well as a greater proportion of DCX-expressing cells with prolongation in hippocampus. Furthermore, the proportion of the mucosa-associated symbiotic bacteria Akkermansia muciniphila increased by 4-14 times in the cecal microbiota of mice fed diets supplemented with lingonberry, bilberry, sea buckthorn, and blueberry. These findings demonstrate the potential of Nordic berries to preserve memory and cognitive function, and to induce alterations of the gut microbiota composition.

Cultivation of the gut bacterium Prevotella copri DSM 18205T using glucose and xylose as carbon sources.

Prevotella copri DSM18205T is a human gut bacterium, suggested as a next-generation probiotic. To utilize it as such, it is, however, necessary to grow the species in a reproducible manner. Prevotella copri has previously been reported to be highly sensitive to oxygen, and hence difficult to isolate and cultivate. This study presents successful batch cultivation strategies for viable strain inoculations and growth in both serum bottles and a stirred tank bioreactor (STR), without the use of an anaerobic chamber, as long as the cells were kept in the exponential growth phase. A low headspace volume in the STR was important to reach high cell density. P. copri utilized xylose cultivated in Peptone Yeast Xylose medium (PYX medium), resulting in a comparable growth rate and metabolite production as in Peptone Yeast Glucose medium (PYG medium) in batch cultivations at pH 7.2.Up to 5 g/L of the carbon source was consumed, leading to the production of succinic acid, acetic acid, and formic acid, and cell densities (OD620 nm ) in the range 6-7.5. The highest yield of produced succinic acid was 0.63 ± 0.05 g/g glucose in PYG medium cultivations and 0.88 ± 0.06 g/g xylose in PYX medium cultivations.

Effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI): study protocol for a randomized, double-blind, placebo-controlled trial.

BACKGROUND: Bilberries from Sweden, rich in polyphenols, have shown cholesterol-lowering effects in small studies, and the cholesterol-lowering properties of oats, with abundant beta-glucans and potentially bioactive phytochemicals, are well established. Both may provide cardiometabolic benefits following acute myocardial infarction (AMI), but large studies of adequate statistical power and appropriate duration are needed to confirm clinically relevant treatment effects. No previous study has evaluated the potential additive or synergistic effects of bilberry combined with oats on cardiometabolic risk factors. Our primary objective is to assess cardioprotective effects of diet supplementation with dried bilberry or with bioprocessed oat bran, with a secondary explorative objective of assessing their combination, compared with a neutral isocaloric reference supplement, initiated within 5 days following percutaneous coronary intervention (PCI) for AMI. METHODS: The effects of Bilberry and Oat intake on lipids, inflammation and exercise capacity after Acute Myocardial Infarction (BIOAMI) trial is a double-blind, randomized, placebo-controlled clinical trial. A total of 900 patients will be randomized post-PCI to one of four dietary intervention arms. After randomization, subjects will receive beverages with bilberry powder (active), beverages with high-fiber bioprocessed oat bran (active), beverages with bilberry and oats combined (active), or reference beverages containing no active bilberry or active oats, for consumption twice daily during a 3-month intervention. The primary endpoint is the difference in LDL cholesterol change between the intervention groups after 3 months. The major secondary endpoint is exercise capacity at 3 months. Other secondary endpoints include plasma concentrations of biochemical markers of inflammation, metabolomics, and gut microbiota composition after 3 months. DISCUSSION: Controlling hyperlipidemia and inflammation is critical to preventing new cardiovascular events, but novel pharmacological treatments for these conditions are expensive and associated with negative side effects. If bilberry and/or oat, in addition to standard medical therapy, can lower LDL cholesterol and inflammation more than standard therapy alone, this could be a cost-effective and safe dietary strategy for secondary prevention after AMI. TRIAL REGISTRATION: ClinicalTrials.gov NCT03620266 . Registered on August 8, 2018.

A novel nutritional supplement containing amino acids and chromium decreases postprandial glucose response in a randomized, double-blind, placebo-controlled study.

High postprandial blood glucose levels are associated with increased mortality, cardiovascular events and development of diabetes in the general population. Interventions targeting postprandial glucose have been shown to prevent both cardiovascular events and diabetes. This study evaluates the efficacy and safety of a novel nutritional supplement targeting postprandial glucose excursions in non-diabetic adults. Sixty overweight healthy male and female participants were recruited at two centers and randomized in a double-blind, placebo-controlled, crossover design. The supplement, a water-based drink containing 2.6g of amino acids (L-Leucine, L-Threonine, L-Lysine Monohydrochloride, L-Isoleucine, L-Valine) and 250 mcg of chromium picolinate, was consumed with a standardized carbohydrate-rich meal. The primary endpoint was the incremental area under the curve (iAUC) for venous blood glucose from 0 to 120 minutes. Secondary endpoints included glucose iAUC 0-180 minutes and the maximum glucose concentration (Cmax), for both venous and capillary blood glucose. In the intention-to-treat-analysis (n = 60) the supplement resulted in a decreased venous blood glucose iAUC0-120min compared to placebo, mean (SE) of 68.7 (6.6) versus 52.2 (6.8) respectively, a difference of -16.5 mmol/L•min (95% CI -3.1 to -30.0, p = 0.017). The Cmax for venous blood glucose for the supplement and placebo were 6.45 (0.12) versus 6.10 (<0.12), respectively, a difference of -0.35 mmol/L (95% CI -0.17 to -0.53, p<0.001). In the per protocol-analysis (n = 48), the supplement resulted in a decreased Cmax compared to placebo from 6.42 (0.14) to 6.12 (0.14), a difference of -0.29 mmol/L (95% CI -0.12 to -0.47, p = 0.002). No significant differences in capillary blood glucose were found, as measured by regular bed-side glucometers. The nutritional supplement drink containing amino acids and chromium improves the postprandial glucose homeostasis in overweight adults without diabetes. Future studies should clarify, whether regular consumption of the supplement improves markers of disease or could play a role in a diet aiming at preventing the development of diabetes.

Alterations in the plasma metabolite profile associated with improved hepatic function and glycemia in mice fed lingonberry supplemented high-fat diets.

SCOPE: Lingonberries have been shown to reduce the detrimental effects of high-fat diet (HFD) on weight gain, plasma glucose, and inflammation. However, the extent of effects was recently shown to vary between different batches of berries. Here, we examine the metabolic response to two independent batches of lingonberries. METHODS AND RESULTS: Alterations in the phenotype and circulating metabolome elicited by three matched HFDs, two of which containing lingonberries (L1D and L2D) from different sources, were investigated. Glycemia was improved only in mice fed L1D, whereas liver function was improved and inflammation reduced in mice fed both L1D and L2D, compared to mice fed HFD. The unique improvement in glycemia elicited by L1D was associated with a 21% increase in circulating levels of fatty acids. Increased levels of phosphatidylcholines (62%) and lysophosphatidylcholines (28%) and decreased levels of serine (-13%) and sphingomyelins (-26%) were observed in mice fed L1D and L2D, as compared to HFD. CONCLUSION: The unique improvement in glycemia in mice fed L1D was associated with a normal metabolic control with an altered set point. Moreover, the batch-independent reduction in liver steatosis and inflammation, was associated with an altered sphingomyelin metabolism.

Lingonberries alter the gut microbiota and prevent low-grade inflammation in high-fat diet fed mice.

BACKGROUND: The gut microbiota plays an important role in the development of obesity and obesity-associated impairments such as low-grade inflammation. Lingonberries have been shown to prevent diet-induced obesity and low-grade inflammation. However, it is not known whether the effect of lingonberry supplementation is related to modifications of the gut microbiota. The aim of the present study was to describe whether consumption of different batches of lingonberries alters the composition of the gut microbiota, which could be relevant for the protective effect against high fat (HF)-induced metabolic alterations. METHODS: Three groups of C57BL/6J mice were fed HF diet with or without a supplement of 20% lingonberries from two different batches (Lingon1 and Lingon2) during 11 weeks. The composition and functionality of the cecal microbiota were assessed by 16S rRNA sequencing and PICRUSt. In addition, parameters related to obesity, insulin sensitivity, hepatic steatosis, inflammation and gut barrier function were examined. RESULTS: HF-induced obesity was only prevented by the Lingon1 diet, whereas both batches of lingonberries reduced plasma levels of markers of inflammation and endotoxemia (SAA and LBP) as well as modified the composition and functionality of the gut microbiota, compared to the HF control group. The relative abundance of Akkermansia and Faecalibacterium, genera associated with healthy gut mucosa and anti-inflammation, was found to increase in response to lingonberry intake. CONCLUSIONS: Our results show that supplementation with lingonberries to an HF diet prevents low-grade inflammation and is associated with significant changes of the microbiota composition. Notably, the anti-inflammatory properties of lingonberries seem to be independent of effects on body weight gain.

Berry intake changes hepatic gene expression and DNA methylation patterns associated with high-fat diet.

The liver is a critical organ for regulation of energy homeostasis and fatty liver disease is closely associated with obesity and insulin resistance. We have previously found that lingonberries, blackcurrants and bilberries prevent, whereas açai berries exacerbate, the development of hepatic steatosis and obesity in the high-fat (HF)-fed C57BL/6J mouse model. In this follow-up study, we investigated the mechanisms behind these effects. Genome-wide hepatic gene expression profiling indicates that the protective effects of lingonberries and bilberries are accounted for by several-fold downregulation of genes involved in acute-phase and inflammatory pathways (e.g. Saa1, Cxcl1, Lcn2). In contrast, açai-fed mice exhibit marked upregulation of genes associated with steatosis (e.g. Cfd, Cidea, Crat) and lipid and cholesterol biosynthesis, which is in line with the exacerbation of HF-induced hepatic steatosis in these mice. In silico transcription factor analysis together with immunoblot analysis identified NF-κB, STAT3 and mTOR as upstream regulators involved in mediating the observed transcriptional effects. To gain further insight into mechanisms involved in the gene expression changes, the HELP-tagging assay was used to identify differentially methylated CpG sites. Compared to the HF control group, lingonberries induced genome-wide hypermethylation and specific hypermethylation of Ncor2, encoding the corepressor NCoR/SMRT implicated in the regulation of pathways of metabolic homeostasis and inflammation. We conclude that the beneficial metabolic effects of lingonberries and bilberries are associated with downregulation of inflammatory pathways, whereas for blackcurrants, exerting similar metabolic effects, different mechanisms of action appear to dominate. NF-κB, STAT3 and mTOR are potential targets of the health-promoting effects of berries.