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Alterations of gut microbiota are associated with blood pressure: a cross-sectional clinical trial in Northwestern China.
Lv, J, Wang, J, Yu, Y, Zhao, M, Yang, W, Liu, J, Zhao, Y, Yang, Y, Wang, G, Guo, L, et al
Journal of translational medicine. 2023;21(1):429
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Hypertension (HTN) is a complex and modifiable risk factor for cardiovascular diseases (CVDs) and stroke, while a diverse range of endogenous and environmental factors contribute to both HTN onset and progression. The adult gut microbiota (GM) consists of trillions of microorganisms and maintains the gut immunity and whole-body homeostasis. The aim of this study was to investigate the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. This study was a cross-sectional study. Participants were randomly selected for the HTN and control groups. A total of 36 HTN subjects (24 females and 12 males) and 18 controls (9 females and 9 males) were randomly selected for metagenomic analysis. Results showed a positive association between GM characteristics and alterations and HTN in both females and males. Thus, GM dysbiosis underlies HTN pathogenesis. Authors conclude that further studies are needed to elucidate the underlying mechanisms and potential therapeutic interventions targeting GM for HTN prevention and management
Abstract
BACKGROUND The human gut microbiota (GM) is involved in the pathogenesis of hypertension (HTN), and could be affected by various factors, including sex and geography. However, available data directly linking GM to HTN based on sex differences are limited. METHODS This study investigated the GM characteristics in HTN subjects in Northwestern China, and evaluate the associations of GM with blood pressure levels based on sex differences. A total of 87 HTN subjects and 45 controls were recruited with demographic and clinical characteristics documented. Fecal samples were collected for 16S rRNA gene sequencing and metagenomic sequencing. RESULTS GM diversity was observed higher in females compared to males, and principal coordinate analysis showed an obvious segregation of females and males. Four predominant phyla of fecal GM included Firmicutes, Bacteroidetes, Actinobacteria and Proteobacteria. LEfSe analysis indicated that phylum unidentified_Bacteria was enriched in HTN females, while Leuconostocaceae, Weissella and Weissella_cibaria were enriched in control females (P < 0.05). Functionally, ROC analysis revealed that Cellular Processes (0.796, 95% CI 0.620 ~ 0.916), Human Diseases (0.773, 95% CI 0.595 ~ 0.900), Signal transduction (0.806, 95% CI 0.631 ~ 0.922) and Two-component system (0.806, 95% CI 0.631 ~ 0.922) could differentiate HTN females as effective functional classifiers, which were also positively correlated with systolic blood pressure levels. CONCLUSIONS This work provides evidence of fecal GM characteristics in HTN females and males in a northwestern Chinese population, further supporting the notion that GM dysbiosis may participate in the pathogenesis of HTN, and the role of sex differences should be considered. Trial registration Chinese Clinical Trial Registry, ChiCTR1800019191. Registered 30 October 2018 - Retrospectively registered, http://www.chictr.org.cn/ .
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Cigarette Smoke Extract Disturbs Mitochondria-Regulated Airway Epithelial Cell Responses to Pneumococci.
Aghapour, M, Tulen, CBM, Abdi Sarabi, M, Weinert, S, Müsken, M, Relja, B, van Schooten, FJ, Jeron, A, Braun-Dullaeus, R, Remels, AH, et al
Cells. 2022;11(11)
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Cigarette smoking can affect airway epithelial cells, causing overproduction of mucus, damage, and inflammation, which may result in the progression of airway diseases. Airway epithelial cells (AEC) rely on mitochondria for energy, and mitochondrial dysfunction may affect innate immunity and the integrity of the airway epithelium. Cigarette smoking is found to accelerate mitochondrial damage within AEC. Maintaining a normal microbial composition within the respiratory tract is essential for maintaining immunity. There is evidence that smoking cigarettes disrupts the microbial composition and increases the spread of pathogenic bacteria such as Streptococcus pneumoniae (Sp) which causes inflammation. By exposing 16HBE cells to Sp and cigarette smoke extract (CSE), this study investigated the effect of cigarette smoking on mitochondrial dysfunction in ACE in an in vitro model. Additionally, the study examined the direct and indirect pathways involved in cigarette smoking-induced mitochondrial dysfunction and altered innate immune response to Sp infection. CSE exposure decreases mitochondrial complex protein levels and mitochondrial membrane potential, which affects energy production. It also increases mitochondrial oxidative stress and mitochondrial degradation. All these factors lead to mitochondrial dysfunction in ACE. CSE exposure to ACE was associated with altered gene expression in the tight and adherence junctions that serve as a protective barrier against pathogens and pollutants and reduced type I interferon immune responses to Sp. Using the results of this study, healthcare professionals can gain a better understanding of the impact of cigarette smoking on mitochondrial dysfunction and how it increases susceptibility to Sp-related immune responses. It is necessary to conduct further studies to evaluate the effects of cigarette smoking on mitochondrial dysfunction, microbial composition disruption, and the interaction between AECs and elevated immune responses.
Abstract
Mitochondrial functionality is crucial for the execution of physiologic functions of metabolically active cells in the respiratory tract including airway epithelial cells (AECs). Cigarette smoke is known to impair mitochondrial function in AECs. However, the potential contribution of mitochondrial dysfunction in AECs to airway infection and airway epithelial barrier dysfunction is unknown. In this study, we used an in vitro model based on AECs exposed to cigarette smoke extract (CSE) followed by an infection with Streptococcus pneumoniae (Sp). The levels of oxidative stress as an indicator of mitochondrial stress were quantified upon CSE and Sp treatment. In addition, expression of proteins associated with mitophagy, mitochondrial content, and biogenesis as well as mitochondrial fission and fusion was quantified. Transcriptional AEC profiling was performed to identify the potential changes in innate immune pathways and correlate them with indices of mitochondrial function. We observed that CSE exposure substantially altered mitochondrial function in AECs by suppressing mitochondrial complex protein levels, reducing mitochondrial membrane potential and increasing mitochondrial stress and mitophagy. Moreover, CSE-induced mitochondrial dysfunction correlated with reduced enrichment of genes involved in apical junctions and innate immune responses to Sp, particularly type I interferon responses. Together, our results demonstrated that CSE-induced mitochondrial dysfunction may contribute to impaired innate immune responses to Sp.
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Serum vitamin E levels and chronic inflammatory skin diseases: A systematic review and meta-analysis.
Liu, X, Yang, G, Luo, M, Lan, Q, Shi, X, Deng, H, Wang, N, Xu, X, Zhang, C
PloS one. 2021;16(12):e0261259
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Vitiligo, Psoriasis, Acne and Atopic Dermatitis are chronic immune-mediated inflammatory skin conditions characterised by itchy skin. In previous studies, decreased serum vitamin E levels have been associated with an increased risk of skin diseases. Nuts, oils from plants, and vegetables contain vitamin E, which is a dietary bioactive compound that has anti-inflammatory and antioxidant properties. In this systematic review and meta-analysis, twenty case-controlled studies were included, of which thirteen specifically examined alpha-tocopherol levels. Psoriasis, Vitiligo, atopic dermatitis, and acne patient groups had significantly lower levels of serum Vitamin E than the control groups. There is no clear understanding of the pathogenesis of chronic inflammatory skin conditions. One of the underlying mechanisms is the interaction between oxidative stress and the immune system, as well as the accumulation of free radicals in the epidermal layers of the skin. As there is limited evidence regarding the benefits of Vitamin E in improving chronic inflammatory skin conditions, further robust studies are necessary. Healthcare professionals can use this research to gain a better understanding of the potential clinical applications of vitamin E in the treatment of skin disorders.
Expert Review
Conflicts of interest:
None
Take Home Message:
- Low serum vitamin E levels are reported to be associated with several chronic inflammatory skin diseases, such as vitiligo, psoriasis, atopic dermatitis, and acne.
- Practitioners could consider vitamin E therapy in those with low serum concentrations
Evidence Category:
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A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
This systematic review and meta-analysis report on the association between serum vitamin E levels and chronic inflammatory skin diseases.
The review which followed PRISMA reporting guidelines, screened 892 studies. After the selection and exclusions, 20 case-control studies were included involving a total of 1172 patients.
The studies that were included focused mainly on chronic inflammatory diseases, including vitiligo, psoriasis, atopic dermatitis, and acne. Eight studies included only adults, five included only children or teenagers and six studies included adults and children. One study had no age description.
Thirteen studies stated that alpha-tocopherol was used in their investigations. However, seven studies did not describe the subunit of vitamin E.
Primary clinical outcomes were:
- Seven studies, with 351 cases and 350 controls reported that compared with the control group, vitiligo patients had lower serum vitamin E concentrations (Standard Mean Difference (SMD):0.70, 95% Cl:121-0.19.
- Six studies investigated the change of serum vitamin E levels in patients with psoriasis, with 278 cases and 257 controls. Compared with the control group, psoriasis patients had lower serum vitamin E concentrations (SMD: -2.37, 95% CI: -3.57 to -1.18).
- The serum vitamin E Levels in patients with atopic dermatitis were observed in 4 studies, with 259 cases and 307 controls. Compared with the control group atopic dermatitis patients had lower serum vitamin E concentrations (SMD: -1.08, 95% CI: -1.80 to -0.36).
Levels of serum vitamin E in acne patients were reported in 3 studies, with 284 cases and 186 controls. Compared with the control group, acne patients had lower serum concentration levels of vitamin E (SMD: -0.67, 95% CI: -1.05 to -0.30).
No publication bias was found in any association (Egger’s test >0.05), though heterogeneity was considerable in every case (I2 > 80%), though this interaction was not significant for acne (p=0.879). Associations were not split by age, or any other cofactor, however sensitivity analyses did not indicate modification of the results.
The authors also assessed the association between skin disease severity and serum vitamin E concentrations. Overall, more severe disease was associated with a lower serum vitamin E concentration (SMD -1.56, 95% CI:-2.53 to -059).
Clinical practice applications:
- Vitamin E has gained the attention of researchers as a potential adjuvant therapy for various skin disorders due to its excellent antioxidant and anti-inflammatory properties.
- This review reports on the low levels of serum vitamin E found in patients with vitiligo, psoriasis, atopic dermatitis, and acne, and also suggests that serum concentrations of vitamin E are lower in those with more severe disease. Based on these findings, practitioners could therefore consider investigating the serum vitamin E levels of patients with inflammatory skin diseases and consider including vitamin E in their treatment protocols if their serum vitamin E levels are low.
Considerations for future research:
- The small number of studies in this review indicates the need for further research to be done on vitamin E and inflammatory skin diseases.
- Although there are reports on the antioxidant and anti-inflammatory properties of vitamin E, further investigations are needed to determine the exact mechanism of action in inflammatory skin diseases.
- Additionally, further investigation is needed to evaluate which chemical forms of vitamin E and their dosage amounts have beneficial effects on inflammatory skin diseases.
Abstract
BACKGROUND Vitamin E has long been linked to skin health, including all of its possible functions in cosmetic products, to its roles in membrane integrity and even the aging process. However, reports on the relationship between serum vitamin E levels and the risk of chronic inflammatory skin diseases have been inconsistent. We performed a systematic review and meta-analysis to evaluate the association between serum vitamin E levels and chronic inflammatory skin diseases. METHODS We searched the PubMed, Web of Science and Scopus databases, with no time limit up to 30.06.2021. Studies examining serum vitamin E levels in patients with chronic inflammatory skin diseases were selected. RESULTS Twenty articles met the inclusion criteria. Compared with controls, a lower vitamin E level was found in patients with vitiligo (SMD: -0.70, 95% CI: -1.21 to -0.19), psoriasis (SMD: -2.73, 95% CI: -3.57 to -1.18), atopic dermatitis (SMD: -1.08, 95% CI: -1.80 to -0.36) and acne (SMD: -0.67, 95% CI: -1.05 to -0.30). CONCLUSIONS Our meta-analysis showed that serum vitamin E levels were lower in patients suffering from vitiligo, psoriasis, atopic dermatitis and acne. This study highlights the need to evaluate vitamin E status to improve its level in patients with skin diseases.
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Effects of a 6 Week Low-Dose Combined Resistance and Endurance Training on T Cells and Systemic Inflammation in the Elderly.
Despeghel, M, Reichel, T, Zander, J, Krüger, K, Weyh, C
Cells. 2021;10(4)
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As age advances, a gradual deterioration of immune function happens termed Immunosenescence, where different components of the immune system make a behavioural shift towards gradual decline. Immune ageing is characterized by changes in the ratio of naive memory T cells and CD4:CD8 and is associated with inflammatory cytokine production, which accelerates inflammatory ageing. This randomised controlled trial aimed to examine the effect of low-dose combined resistance and endurance training on the ageing immune system and inflammation in elderly subjects. Thirty participants (between the ages of 65 and 75) took part in a controlled low-threshold and care-oriented combined resistance and endurance training program for six weeks. This study showed an increase in CD4:CD8 ratio, decrease in low-grade inflammation and an improvement in strength capacity denoting improved immunosenescence and inflammaging among elderly participants. However, the study was conducted on a small sample for a short period. Therefore, robust long-term studies are required to elucidate further positive effects of different levels of physical activities in the elderly. Healthcare professionals can use these findings to understand how exercise influences immunosenescence and inflammation in the ageing body.
Abstract
With increasing age, the immune system undergoes a remodeling process, affecting the shift of T cell subpopulations and the development of chronic low-grade inflammation. Clinically, this is characterized by increased susceptibility to infections or development of several diseases. Since lifestyle factors can play a significant role in reducing the hallmarks of immune aging and inflammation, we investigated the effect of a 6 week low-dose combined resistance and endurance training program. Forty participants (70.3 ± 5.0 years) were randomly assigned to either a training (TG) or control group (CG) and performed a controlled low-threshold and care-oriented 6-week-long combined resistance and endurance training program. Changes in anthropometrics as well as strength capacity were measured. In subgroups of TG and CG, T cells and their subpopulations (CD4+, CD8+, naïve, central, effector memory, T-EMRA) were analyzed by flow cytometry. The changes of various plasma cytokines, chemokines, growth factors and adipokines were analyzed by luminex assays. The exercise program was followed by an increase in strength capacities. Participants of TG showed an increase of the CD4+/CD8+ T cell ratio over time (p < 0.05). Significant decreases in systemic levels of interleukin (IL-) 6, IL-8, IL-10 and vascular endothelial growth factor (VEGF) (p < 0.05) were observed for participants of TG over time. Even short-term and low-threshold training can reduce some of the hallmarks of immune aging in elderly and thus could be beneficial to stimulate immunity. The specific characteristics of the program make it easily accessible to older people, who may benefit in the longer term in terms of their immunocompetence.
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Gut microbiota alterations associated with reduced bone mineral density in older adults.
Das, M, Cronin, O, Keohane, DM, Cormac, EM, Nugent, H, Nugent, M, Molloy, C, O'Toole, PW, Shanahan, F, Molloy, MG, et al
Rheumatology (Oxford, England). 2019;58(12):2295-2304
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Osteoporosis, characterised by reduced bone density or ‘brittle bones’ affects a significant number of individuals over the age of 50 worldwide. Contributing factors include calcium and vitamin D deficiency and the presence of other inflammatory conditions. The composition of gut bacteria, the gut microbiome, plays an important role in immune activity and changes in composition have been associated with other inflammatory conditions. This cohort study of 181 individuals at high risk of reduced bone density and fractures, aimed to determine whether different gut microbiota composition is associated with bone density. Dexa scans and faecal samples were used as part of the assessment and confounding factors of diet, BMI, supplementation and medication were included in the analysis. The authors of the study found 6 species of gut bacteria that were significantly altered in numbers in the groups with osteoporosis and osteopenia, after controlling for confounding factors, and suggest that they could be used as markers of disease risk or progression and as a therapeutic target. Nutrition Practitioners working with bone density can focus on supporting the gut microbiome as part of their nutrition protocols.
Abstract
OBJECTIVE To investigate compositional differences in the gut microbiota associated with bone homeostasis and fractures in a cohort of older adults. METHODS Faecal microbiota profiles were determined from 181 individuals with osteopenia (n = 61) or osteoporosis (n = 60), and an age- and gender-matched group with normal BMD (n = 60). Analysis of the 16S (V3-V4 region) amplicon dataset classified to the genus level was used to identify significantly differentially abundant taxa. Adjustments were made for potential confounding variables identified from the literature using several statistical models. RESULTS We identified six genera that were significantly altered in abundance in the osteoporosis or osteopenic groups compared with age- and gender-matched controls. A detailed study of microbiota associations with meta-data variables that included BMI, health status, diet and medication revealed that these meta-data explained 15-17% of the variance within the microbiota dataset. BMD measurements were significantly associated with alterations in the microbiota. After controlling for known biological confounders, five of the six taxa remained significant. Overall microbiota alpha diversity did not correlate to BMD in this study. CONCLUSION Reduced BMD in osteopenia and osteoporosis is associated with an altered microbiota. These alterations may be useful as biomarkers or therapeutic targets in individuals at high risk of reductions in BMD. These observations will lead to a better understanding of the relationship between the microbiota and bone homeostasis.
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What is the effect of a Mediterranean compared with a Fast Food meal on the exercise induced adipokine changes? A randomized cross-over clinical trial.
Silva, D, Moreira, R, Beltrão, M, Sokhatska, O, Montanha, T, Pizarro, A, Garcia-Larsen, V, Villegas, R, Delgado, L, Moreira, P, et al
PloS one. 2019;14(4):e0215475
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Unhealthy dietary intake and sedentary behaviour in a genetically susceptible individual have been associated with adipokine dysregulation (adipokines are small proteins secreted by the fat tissue) resulting both in adverse metabolic and immune responses. The aim of this study was to evaluate the effect of a Mediterranean (MdM) compared with a Fast Food (FFM) iso-energy meal on the acute exercise-induced adipokine changes. The study is a double-blind randomised crossover clinical trial. Participants (n = 46) were randomly assigned to the intervention order in a double-blinded fashion, stratified by asthma diagnosis. Outcomes were measured blinded to the participant’s allocation order. Results indicate that MdM may blunt the adipsin (an adipokine) immediate response and potentiate its exercise induced increase in comparison with a FFM. MdM slightly attenuated the exercise induced cortisol increase. Authors conclude that their findings highlight the importance of the pre-exercise dietary intake on both the immune and metabolic response to acute exercise.
Abstract
BACKGROUND Adipose tissue-derived adipokines are pro-inflammatory cytokines involved in metabolic-related diseases and can be influenced by diet and exercise. We aimed to compare the effect of a Mediterranean (MdM) compared with Fast Food (FFM) meal on the exercise induced adipokines changes. METHODS In a double blinded cross over trial, 46 participants were randomly assigned to one of two standardized iso-energy pre-exercise meals: FFM or MdM-type. Three hours after each meal, participants completed a treadmill exercise test (EC). Serum adiponectin, resistin, PAI-1, lipocalin-2/NGAL and adipsin were determined by Luminex magnetic bead immunoassay. Wilcoxon signed rank test compared changes before/after meal and before/after EC and a linear mixed model evaluated the effect of meals on the adipokine response to exercise, adjusted for confounders. RESULTS Thirty-nine participants (mean age of 25, with a standard deviation of 5 years) completed the trial (56% females). For both interventions, a significant reduction of adipsin after each meal and a significant increase of lipocalin, PAI-1, adipsin and resistin, after exercise was observed. When exercise was preceded by a MdM meal a higher increase in adipsin levels was seen. CONCLUSION Acute exercise induced an increase of circulatory levels of adipsin, resistin, lipocalin and PAI-1, but not adiponectin. A pre-exercise Mediterranean meal potentiated the increase of adipsin after the exercise test, which possibly relates to the immune regulatory role of adipsin. These changes suggest a cross-talk between the immune and metabolic immediate response to exercise and its modulation by the pre-exercise diet composition.