Gut Microbes Are Associated with the Vascular Beneficial Effects of Dietary Strawberry on Metabolic Syndrome‐Induced Vascular Inflammation

Molecular Nutrition & Food Research · 2022 · 15 citations

• Biology
• Internal medicine
• Endocrinology

SCOPE: Metabolic syndrome (MetS) alters the gut microbial ecology and increases the risk of cardiovascular disease. This study investigates whether strawberry consumption reduces vascular complications in an animal model of MetS and identifies whether this effect is associated with changes in the composition of gut microbes. METHODS AND RESULTS: Seven-week-old male mice consume diets with 10% (C) or 60% kcal from fat (high-fat diet fed mice; HF) for 12 weeks and subgroups are fed a 2.35% freeze-dried strawberry supplemented diet (C+SB or HF+SB). This nutritional dose is equivalent to ≈160 g of strawberry. After 12 weeks treatment, vascular inflammation is enhanced in HF versus C mice as shown by an increased monocyte binding to vasculature, elevated serum chemokines, and increased mRNA expression of inflammatory molecules. However, strawberry supplementation suppresses vascular inflammation in HF+SB versus HF mice. Metabolic variables, blood pressure, and indices of vascular function were similar among the groups. Further, the abundance of opportunistic microbe is decreased in HF+SB. Importantly, circulating chemokines are positively associated with opportunistic microbes and negatively associated with the commensal microbes (Bifidobacterium and Facalibaculum). CONCLUSION: Dietary strawberry decreases the abundance of opportunistic microbe and this is associated with a decrease in vascular inflammation resulting from MetS.

Antibiotics and High‐Fat‐Diet Induced Gut Inflammation and Impaired Gut Permeability are Improved by Dietary Blueberries Possibly Through NFκB Signaling

The FASEB Journal · 2022 · 2 citations

• Chemistry
• Endocrinology
• Internal medicine

Background Evidence indicates that a high fat diet can promote gut inflammation and increase gut permeability. The use of antibiotics further exacerbates these complications and can lead to the development of inflammatory bowel disease. Blueberries are rich in bioactive components such as anthocyanins. We recently reported the vascular and prebiotic effects of dietary blueberries. However, the effects of blueberries on gut inflammation and permeability are unknown. In the present study, we tested the hypothesis that blueberries improve antibiotics and high‐fat‐diet (HFD) induced gut inflammation and impaired gut barrier function in C57BL/6J mice. Methods 7‐week‐old male mice (Jackson Lab) consumed standard diet (10% kcal fat) (CON) or HFD (60% kcal fat) with antibiotic cocktail (ampicillin, vancomycin, neomycin sulfate and metronidazole) in drinking water (HFA) or 3.7% freeze‐dried blueberry powder supplemented HFD with antibiotic cocktail in drinking water (HFA+BB) for 12 weeks. Body weight and body composition were assessed at the end of the experiment. Inflammation and permeability of the colon were assessed by the mRNA expression of inflammatory markers (IL‐1β, IL‐6, iNOS, MCP‐1); gut barrier markers (MUC‐2, cldn‐1 and TJP‐10); and markers of NFκB signaling (p65, IKK‐ β and IκBα) by qPCR using specific primers and SYBR green. Results HFA mice had an increased body weight, reduced lean body mass, and increased body fat compared to CON mice. Blueberry supplementation did not alter these metabolic parameters in HFA+BB vs HFA mice. mRNA expression of inflammatory markers (IL‐1β, iNOS, MCP‐1); gut barrier marker MUC‐2; and markers of NFκB signaling (p65 and IκBα) were increased in HFA vs CON mice. However, blueberry supplementation improved inflammation and permeability of the colon as shown by a reduced colonic expression of IL‐1β, iNOS, MCP‐1 and MUC‐2 in HFA+BB vs HFA mice. Further, a reduced mRNA expression of p65 and IκBα in HFA+BB vs HFA mice indicates that the protective effect of blueberry on the colon could be mediated through NFκB signaling. Conclusion Blueberry supplementation suppresses colon inflammation and ameliorates colon permeability possibly through NFκB Signaling. Consumption of blueberry is a potential dietary approach to improve gut health.

Gut Microbial and Metabolic Signatures are Altered in Adolescents with Type 1 Diabetes

The FASEB Journal · 2022 · 2 citations

• Biology
• Zoology
• Genetics

Background Evidence suggests that the pathogenesis and development of Type 1 Diabetes (T1D) are driven by both genetic predisposition and immune dysfunction which may be influenced by gut microbiota. The present study aimed to investigate the composition and functional pathways of the gut microbiome in adolescents with T1D, determine the association between gut microbes and clinical and dietary factors in T1D, and identify features predictive of T1D. Methods Healthy adolescents (n=35) and adolescents with T1D (n=30) were recruited and microbial profiling in participants’ stool samples was performed using deep shotgun metagenomic sequencing. The bioBakery3 pipeline (Kneaddata, Metaphlan3 and HUMAnN) was used to analyze the reads to assign taxonomy and functional annotations. The differences in taxonomic abundances were identified using Linear Discriminant Analysis (LDA) Effect Size (LEfSe) and ecological measures (diversity) were assessed using standard methods. The association between the abundance of specific bacterial species and the metadata (HbA1C, skin carotenoids, diet and physical activity) was assessed by performing Spearman’s correlation. Random forest modeling (using the MUVR package) was used to identify features predictive of T1D. Results Adolescents with T1D exhibited a significant increase in Simpson α‐diversity index as compared to healthy adolescents. β‐diversity was similar between the two groups. LEfSe indicated a significant difference in the microbial community at different taxonomic levels between the two groups. Seven taxa were enriched in adolescents with T1D at the species level that includes Alistipes Shahii , Asaccharobacter celatus , Blautia obeum , Coprococcus eutactus , Coprobacillus cateniformis , Clostridium symbiosum , and Eggerthella lenta . Three species Alistripes Putredins , Dialister invisus , and Eubacterium ventriosum were enriched in healthy adolescents. Further, 33 out of 400 microbial metabolic pathways were significantly different between the two groups. Importantly, biosynthesis of amino acids, vitamins, enzyme cofactors, and electron carrier were downregulated whereas fermentation pathways were upregulated in adolescents with T1D as compared to healthy adolescents. Association analysis indicated that specific bacterial species are correlated with HbA1C, skin carotenoids, dietary factors and physical activity. Most of the bacterial species associated with these measures were different between the two groups. MUVR identified bacterial taxa predictive of T1D status (0.82 sensitivity and 0.63 specificity). The top features in using genus level abundance included Coprococcus , Faecalibaterium and Streptococcus . Conclusion The present study indicates an extensive alteration in the composition and functional capacity of gut microbiota in adolescents with T1D providing new insight into microbial and metabolic signatures in adolescents with T1D.

Dietary Blueberries Improve Vascular Inflammation and Alter the Composition of the Gut Microbiome in Aged Mice

The FASEB Journal · 2022

• Medicine
• Internal medicine
• Endocrinology

Background Aging is a risk factor for cardiovascular diseases, which are major causes of disability and mortality in the elderly. Endothelial dysfunction and an imbalanced gut microbial ecology play a pivotal role in aging‐associated vascular complications. Dietary change may be an effective strategy to improve vascular health. In this study, we tested the hypothesis that dietary blueberries ameliorate vascular complications and gut dysbiosis in aged mice. Methods Aged mice (17‐month‐old C57BL/6J male, Jackson Laboratory) were fed a control diet (O) or freeze‐dried wild blueberry powder supplemented diet (3.8% in diet) (OB) for 15 weeks. Young mice (2‐month‐old) consumed a control diet (Y) or blueberry supplemented diet (YB) for an identical duration. Based on normalization to body surface area, the blueberry dose is equivalent to 1.5 human servings of blueberry (~240 g) per day. Metabolic parameters, vascular function and vascular inflammation were assessed at the end of the treatment period. Vascular inflammation was assessed by measuring the binding of fluorescent labelled mouse monocytic WEHI78/24 cells to the vascular endothelium. Mesenteric arteries were used to assess vascular function using isometric procedures. Microbial profiling was done using 16s rRNA amplification. Results Metabolic parameters such as body weight, food intake and blood glucose were similar among the groups. Old mice (O) exhibited improved glucose tolerance compared to young mice (Y). Blueberry supplementation did not alter glucose tolerance in young (YB) or old mice (OB). O vs Y had increased monocyte binding to vascular endothelium indicating enhanced vascular inflammation, but this was reduced by blueberry supplementation in OB vs O. Endothelium‐dependent vasorelaxation to acetylcholine and endothelium‐independent vasorelaxation to sodium nitroprusside were similar among the groups. Microbial profiling indicated changes in the composition of gut microbiome among the groups. α‐diversity indices such as Chao and observed species were similar at the phylum level but were different at the genus level among groups. β‐diversity, which represents compositional differences among groups, was different at the phylum and genus levels. Further, the relative abundance of gut microbes at different taxa levels were altered between O vs Y and OB vs O mice. Importantly, the relative abundance of genera Candidatus Saccharimonas and Enterorhabdus were decreased whereas Muribaculum was increased in O vs Y mice. Blueberry supplementation improved the relative abundance of these three genera in OB vs O mice. Conclusion Blueberry supplementation improves aging induced vascular inflammation in C57BL/6J mice without altering the metabolic milieu indicating the direct effect of blueberries on vasculature. Our study also provides evidence for changes in the composition of gut microbiome which might mediate some of the effects of blueberry supplementation in aged mice.