The global obesity epidemic has necessitated the search for better intervention strategies including the exploitation of the health benefits of some gut microbiota and their metabolic products. Therefore, we examined the gut microbial composition and mechanisms of interaction with the host in relation to homoeostatic energy metabolism and pathophysiology of dysbiosis-induced metabolic inflammation and obesity. We also discussed the eubiotic, health-promoting effects of probiotics and prebiotics as well as epigenetic modifications associated with gut microbial dysbiosis and risk of obesity. High-fat/carbohydrate diet programmes the gut microbiota to one predominated by Firmicutes (Clostridium), Prevotella and Methanobrevibacter but deficient in beneficial genera/species such as Bacteroides, Bifidobacterium, Lactobacillus and Akkermansia. Altered gut microbiota is associated with decreased expression of SCFA that maintain intestinal epithelial barrier integrity, reduce bacterial translocation and inflammation and increase expression of hunger-suppressing hormones. Reduced amounts of beneficial micro-organisms also inhibit fasting-induced adipocyte factor expression leading to dyslipidaemia. A low-grade chronic inflammation (metabolic endotoxaemia) ensues which culminates in obesity and its co-morbidities. The synergy of high-fat diet and dysbiotic gut microbiota initiates a recipe that epigenetically programmes the host for increased adiposity and poor glycaemic control. Interestingly, these obesogenic mechanistic pathways that are transmittable from one generation to another can be modulated through the administration of probiotics, prebiotics and synbiotics. Though the influence of gut microbiota on the risk of obesity and several intervention strategies have been extensively demonstrated in animal models, application in humans still requires further robust investigation.

Background: Observational studies suggest links between reduced serum 25(OH)D concentration and increased cardiometabolic disease risk. However, these studies provide limited evidence of causation, with few conclusive randomised controlled trials (RCT) having been carried out to date. This RCT investigated the effect of vitamin D 3 supplementation on vascular function and cardiometabolic disease risk markers, in 55 healthy males aged 18-65 years with plasma 25(OH)D concentration <75 mol L -1 and body mass index ≥24.9 kg m -2 . Methods: Participants were assigned to consume 125 µg day -1 (5000 IU day -1 ) vitamin D 3 or placebo for 8 weeks. Blood samples and vascular function measures were obtained at baseline, as well as at weeks 4 and 8. The primary outcome was arterial stiffness, an indicator of cardiovascular disease (CVD) risk, assessed by pulse wave velocity. Biomarkers of CVD risk, insulin resistance and endothelial function were measured using an enzyme-linked immunosorbent assay. Results: Daily oral intake of 125 µg supplemental vitamin D 3 led to a significant improvement in plasma 25(OH)D concentrations over the 8-week intervention in the vitamin D group compared to the change in the placebo group (p ˂ 0.001). In the vitamin D group, the baseline mean ± SD 25(OH)D concentration was 38.4 ± 15.9 and this increased to 72.8 ± 16.1 nmol L -1 after 8 weeks of supplementation. The intervention had no effect on arterial stiffness, as measured by pulse wave velocity, although vitamin D 3 supplementation did lead to a decrease in mean ± SD brachial pulse pressure from baseline to 8 weeks of −2.9 ± 3.4 mmHg (p = 0.027) in the vitamin D group compared to the same period in the placebo group. The intervention had no effect on the remaining cardiometabolic parameters. Conclusions: Overall, treatment significantly improved brachial pulse pressure but no other cardiometabolic disease risk markers. To follow on from this pilot RCT, future large-scale clinical trials over longer durations may offer further insights.

Sickle cell disease (SCD) poses an increased risk of infertility, pregnancy complications and maternal and perinatal mortality among women of reproductive age. This risk is particularly higher for women in sub-Saharan Africa, where the disease burden is highest and access to comprehensive health care is limited, as well as in other countries with a high SCD prevalence due to migration. Disease modifying treatments for SCD could directly and indirectly harm the ovaries, potentially compromising quality and quantity of existing oocytes. Therefore, it is essential to explore alternative interventions, such as nutritional modifications that are less harmful and cost-effective in order to improve reproductive outcomes, and enhance the overall well-being of both mother and child in this population. Maintaining optimal levels of B12 may possibly provide benefits to the ovaries and pregnancy by decreasing homocysteine levels, increasing nitric oxide (NO) bioavailability, and promoting antioxidant and anti-inflammatory activities. Individuals living with SCD are more susceptible to vitamin B12 (B12) deficiency. However, there is a lack of clinical data investigating the relationship between systemic levels of B12, its supplementation, and reproductive outcome measures in SCD women. Therefore, this review aims to examine the current evidence regarding the impact of SCD on female reproductive health and the role of B12 in the reproductive biology of women living with SCD.

Purpose Lassa fever is a zoonotic acute viral hemorrhagic disease caused by Lassa virus (LASV). There is currently no licensed vaccine for the prevention of the disease. This study is aimed at discovering immunodominant epitopes from the envelope glycoprotein of the Lassa mammarenavirus and designing of a multi-epitope vaccine candidate (VC). Materials and Methods The amino acid sequences of the envelope glycoprotein of 26 strains of LASV from five countries were selected. After evaluation for antigenicity, immunogenicity, allergenicity, and toxicity, immunodominant CD8, CD4, and linear B lymphocytes were also selected. The selected epitopes were modelled and a molecular docking with the appropriate major histocompatibility complex (MHC) proteins was performed. Using an adjuvant and linkers, a multi-epitope VC was designed. The VC was evaluated for its physicochemical and immunological properties and structurally refined, validated, and mutated (disulphide engineering). The complex formed by the VC and the toll-like receptor-4 receptor was subjected to molecular dynamic simulation (MDS) followed by in silico cloning in a plasmid vector. Results A VC with 203 sequences, 22.13 kDa weight, isoelectric point of 9.85 (basic), instability index value of 27.62, aliphatic index of 68.87, and GRAVY value of -0.455 (hydrophilic) emerged. The VC is predicted to be non-allergenic with antigenicity, MHC I immunogenicity, and solubility upon overexpression values of 0.81, 2.04, and 0.86 respectively. The VC also has an estimated half-life greater than 10 hours in Escherichia coli and showed stability in all the parameters of MDS. Conclusion The VC shows good promise in the prevention of Lassa fever but further tests are required to validate its safety and efficacy.