The gut microbiota is a metabolically active ecosystem that influences host physiology through bioactive metabolites and interactions with host signaling pathways. Recent research has established a bidirectional gut-muscle axis in which microbial metabolites and muscle-derived factors (myokines) regulate muscle protein synthesis, degradation, regeneration, fiber-type specification, and overall muscle performance. Studies using germ-free, antibiotic-treated, probiotic-supplemented, and fecal microbiota transplantation models demonstrate that the gut microbiota is a critical determinant of skeletal muscle mass and function. Key mediators include short-chain fatty acids, bile acids, aromatic amino acid metabolites, microbial-associated molecular patterns, and methylamine metabolites. This review summarizes current mechanistic knowledge of gut-muscle communication and its relevance to livestock production. In monogastric livestock, particularly pigs and poultry, microbiota transplantation experiments and targeted probiotic interventions provide causal evidence that gut microbial communities influence muscle growth, muscle fiber composition, intramuscular fat deposition, carcass traits, and meat quality, including tenderness, marbling, water-holding capacity, and flavor. Several studies have also identified specific microbial taxa and metabolites capable of transferring desirable production phenotypes. In contrast, evidence in ruminants remains largely associative and originates mainly from multi-omics and dietary intervention studies. Future research should validate causal mechanisms, identify robust microbial biomarkers, and develop species-specific microbiome-based strategies for precision livestock production.

While β-glucans from plants and yeasts have been extensively studied in weaned piglets, studies examining algae β-glucans are scarce. Thus, the present study aimed to examine the effects of feeding algae β-glucan in weaned piglets. Male, 21-day-old, weaned crossbred piglets were allotted to three experimental groups, which were fed either an adequate basal diet (Control) or the basal diet supplemented with 100 (A100) or 200 g/t (A200) of algae β-glucan for 35 days. Performance parameters, apparent total tract digestibility of nutrients, gut morphology metrics, gut mucosa mRNA levels of most genes involved in gut function and integrity, and the number of different immune cells in the proximal jejunum did not differ across groups after 35 days. In the mid-jejunum, the number of lymphocytes in the lamina propria was higher in the A200 group than in the other two groups (p < 0.05) after 35 days. Mucosa score for mucosa fibrosis, villous stunting and villous epithelial injury in the duodenum and the proximal and mid-jejunum were not different across groups after 35 days. The proportion of acetate was higher, and that of valerate was lower in the colon digesta of the A200 group than in the other two groups (p < 0.05). While the abundance of Prevotella spp. was lower in the A200 group than in the other groups (p < 0.05), the abundance of Bifidobacterium spp., Clostridium-leptum-group, Faecalibacterium prausnitzii and Lactobacillus spp. in the colon digesta did not differ across groups after 35 days. In conclusion, feeding algae β-glucan to healthy weaned piglets marginally influences gut-associated parameters and the abundance of selected bacterial groups and the bacterial fermentation pattern in the colon digesta but has no effect on growth performance.

Abstract Background Subclinical atherosclerotic plaque (SAP) develops silently in older adults. Biological changes that predict plaque formation are not well defined. We examined whether circulating immunological, metabolic, and functional measures identify vascular vulnerability before clinical disease. Methods In a three-year longitudinal study, 49 healthy older adults (63.8 ± 3.8 years) underwent carotid ultrasound, T cell phenotyping, serum protein profiling, body composition assessment, and fitness testing at baseline and follow-up. At follow-up, participants were classified as no SAP, new SAP or persistent SAP. We analyzed baseline determinants and within-person changes to predict incident plaque formation. Results New SAP occurred in 30.3% of those initially plaque-free. At baseline, lower frequencies of CD8 + effector memory (EM) T cells and higher frequencies of CD8 + effector memory re-expressing CD45RA (EMRA) T cells and regulatory T cells (Tregs) were associated with higher odds of new SAP. Over time, expansion of CD8 + EM T cells was the most consistently associated independent variable of new SAP, accompanied by declines in Tregs and in the Treg/Teff ratio. Vascular cell adhesion molecule-1 (VCAM-1) at baseline was an additional independent predictor. Increases in visceral fat and declines in VO 2 peak were linked to new SAP, but immune markers were more robust than metabolic variables or serum cytokines. Conclusion Adaptive immune remodeling follows a phase-dependent pattern in which CD8 + EM reductions and later CD8 + EM expansion with Treg decline signal emerging vascular vulnerability. These immune signatures, together with VCAM-1, may help characterize vascular vulnerability during the subclinical phase of plaque development.

Aging is accompanied by functional decline and immune remodeling, yet the dynamics and early modifiability of these processes remain incompletely understood. Research suggests that lifestyle factors, particularly physical activity and fitness, influence immune aging. This study investigated longitudinal changes in physical performance and immune parameters in a well-characterized cohort of clinically healthy elderly. In this study, 49 clinically healthy elderly underwent repeated assessments of cardiorespiratory fitness, muscular strength, body composition, immune cell phenotypes, and serum cytokines at baseline, 1-year, and 3-year follow-up. We observed a shift toward an aged T cell profile, characterized by reductions in naïve and regulatory T cells (Tregs), alongside increases in differentiated and senescence-associated subsets. Treg subsets followed divergent trajectories, with resting Tregs (rTregs) declining and memory-like Tregs (mTregs) increasing. Serum levels of classical pro-inflammatory cytokines remained largely stable over the study period. Despite stable self-reported physical activity, participants showed declines in cardiorespiratory fitness and strength. Immune remodeling was primarily associated with declines in physical fitness, alongside an increase in highly differentiated CD4+ and senescent CD8+ T cell subsets, lower rTregs, higher mTregs, and increased CD4-CD8- lymphocyte frequencies, while habitual physical activity was independently related to effector T cell dynamics. Together, these findings indicate that subtle functional decline in clinically healthy older adults is paralleled by immune changes characteristic of early immunosenescence, occurring largely in the absence of overt systemic inflammation. These results highlight physical fitness as a potentially modifiable determinant of immune trajectories and immune resilience in healthy aging.

Mitochondrial function plays a central role in regulating immunological and metabolic processes, particularly during successful aging. This cross-sectional study aimed to investigate associations between mitochondrial respiration of peripheral blood mononuclear cells (PBMCs; MRPBMC) and key markers of immune function, systemic inflammation, and metabolic health in a cohort of healthy older adults. Sixteen healthy, physically active participants aged > 55 years (male: n = 9; female: n = 7; age: 64 ± 3.7 years; BMI: 24.3 ± 2.9; VO2peak: 31.1 ± 8.8 mL/min/kg) were recruited. Participants were tested for their maximal oxygen uptake (VO2peak) as well as cardiovascular and metabolic risk factors. Venous fasting blood samples were collected. For further analysis, MRPBMC was measured using the Oroboros O2k-Oxygraph. T cell subsets were analyzed by flow cytometry, serum cytokines by LUMINEX assays, and gene expression by qPCR analysis. We found positive associations between basal and maximal MRPBMC, and the percentage of CD4+ T cells, with a notable link to naïve CD4+ T cells (p < 0.05). Maximal MRPBMC was negatively associated with proportion of effector memory CD4+ T cells (p < 0.05). Basal MRPBMC showed negative associations with pro-inflammatory serum cytokine tumor necrosis factor alpha (TNF-α), while maximal MRPBMC was positively associated with interleukin 8 (IL-8), intercellular adhesion molecule 1 (ICAM-1), and vascular endothelial growth factor (VEGF) (p < 0.05). Intracellular signaling markers, including mRNA level of signal transducer and activator of transcription 3 (STAT3), also showed positive associations with maximal MRPBMC (p < 0.05). No correlations were found for variables such as cardiorespiratory fitness, IL-6, and IL-10. In conclusion, PBMC mitochondrial bioenergetics are linked to T cell subpopulations and systemic inflammation in healthy older adults. Higher mitochondrial respiration reflecting better mitochondrial function favors a more naïve CD4+ T cell distribution. In contrast, lower mitochondrial function was observed in individuals with a more pro-inflammatory profile, suggesting a potential relationship between immune status and mitochondrial bioenergetics in older adults.

Biomass from cultivated edible mushrooms can be sustainably produced using residual lignocellulosic sidestreams from agri-industrial and wood processing and is a rich source of a variety of bioactive compounds. While edible mushrooms have a long history as a tasty and healthy food for humans, the potential of mushrooms (fungal fruiting bodies), fungal mycelia and by-products from mushroom production (stem residues, spent mushroom substrate) as feed component for poultry is less acknowledged. Based on this, the present review aims to describe the role of filamentous fungi in circular feed production, characterise the nutritional value of fungal biomass, and provide up to date evidence about the efficacy of feeding fungal biomass on performance of broilers. Feeding studies with healthy and parasite-infected broilers using fungal fruiting bodies, mycelia, stem residues or spent mushroom substrate nearly equally showed either positive or neutral effects on growth performance, whereas impairments of performance and carcass parameters were not reported. Improvements of broiler performance in response to feeding fungal biomass were at least partially associated with a beneficial modulation of the gut microbiota community structure - effects that are most likely attributed to the presence of fermentable polysaccharides and phenolic compounds with prebiotic and selective antimicrobial activities, respectively. Based on the evidence from literature presented in this review, the inclusion of fungal biomass, particularly inexpensive by-products from mushroom production like stem residues and spent mushroom substrate, in broiler diets can be recommended, because even if no growth-promoting effects are induced the partial replacement of less sustainably produced feed components by fungal biomass improves the environmental impact of broiler production. Considering that the number of broiler studies showing either positive or neutral effects of fungal biomass on growth performance is broadly balanced and divergent study outcomes are reported even for biomass from the same fungal species, future studies are necessary to identify the specific requirements of fungal biomass responsible for promoting broiler performance.

Previous studies have demonstrated that high-yielding dairy cows experience endoplasmic reticulum (ER) stress in the liver during early lactation. To date, most insights into the role of ER stress in metabolism and disease pathophysiology have been derived from rodent and human models. In dairy cattle, however, the specific impact of ER stress on metabolic pathways and its contribution to disease development remain insufficiently characterized. The objective of this study was therefore to investigate the molecular effects of ER stress using a bovine liver cell model (BFH12 cells). ER stress was induced by incubation with Tunicamycin (TM) and Thapsigargin (TG). Molecular responses to ER stress were assessed via a whole-genome array analysis and PCR targeting genes involved in selected metabolic pathways. Incubation with both ER stress inducers resulted in a marked upregulation of genes associated with the unfolded protein response (UPR) within a 4 to 24-h time frame, indicative of the production of robust ER stress in these cells. Unexpectedly, treatment with TM led to a downregulation of numerous genes involved in lipid biosynthesis, including those related to lipogenesis and cholesterol synthesis. Furthermore, incubation with TM and TG induced upregulation of genes involved in fatty acid oxidation and was accompanied by a reduction in intracellular triglyceride concentrations. Genes associated with inflammatory responses were upregulated by both TM and TG, whereas genes encoding antioxidant enzymes were downregulated. Genes involved in ketogenesis did not exhibit a consistent pattern of regulation. Overall, several effects of ER stress previously described in rodent models could not be replicated in this bovine liver cell system. Extrapolating these findings to dairy cows suggests that while ER stress may contribute to hepatic inflammation, it is unlikely to play a significant role in the development of hepatic lipidosis or ketosis.

High-yielding farm animals often face severe metabolic stress, compounded by environmental stressors such as psychosocial stress, heat stress, intensive housing systems, and poor hygiene management. These factors result in oxidative stress and inflammatory processes, which adversely affect both animal health and performance. Polyphenols are known to alleviate both oxidative stress and inflammatory responses. Since grapes are rich in polyphenols, by-products of winemaking could have beneficial effects on these processes. This review aims to provide an overview of the potential antioxidative and anti-inflammatory effects of grape by-products in farm animals. The first section of the review examines the causes and consequences of oxidative stress and inflammation. The second section highlights the general effects of polyphenols in addressing these issues. The third and central part of the review presents an overview of findings from studies investigating the impact of various grape-derived polyphenols on the antioxidant system and inflammation in pigs, chicken, and cattle. Overall, these studies demonstrate that grape by-products can effectively reduce oxidative stress and inflammation in pigs and chickens, often leading to improved performance. In cattle, however, fewer studies have been conducted, and the results regarding oxidative stress and inflammation are less consistent. In conclusion, grape by-products represent valuable feed options for preventing oxidative stress and inflammation in monogastric farm animals (pigs, chickens).

By-products from winemaking, such as grape pomace, grape seeds, grape skins, or extracts made from them, represent a cost-effective and sustainable bioresource. These by-products are a source of polyphenolic compounds, plant fibers and—in the case of seeds—essential fatty acids with various health-promoting effects for livestock. Numerous studies involving fast-growing broiler breeds—which often suffer from metabolic inflammation and oxidative stress due to disproportionate breast muscle growth leading to issues like cardiorespiratory insufficiency—indicate that supplementing feed with grape by-products improves performance, particularly weight gain and feed efficiency. This literature review demonstrates that the performance-enhancing effects of grape by-products in fast-growing broiler breeds can be attributed to various mechanisms such as improved nutrient digestibility, a positive influence on intestinal morphology and integrity, the favorable modulation of the microbial community in the gut, the inhibition of oxidative stress or the enhancement of the antioxidant defense system, and the stimulation of the immune response.

The study aimed to investigate early immunological and molecular changes in a homogeneous group of healthy older individuals, initially screened to categorize them into groups with or without subclinical carotid artery plaque. Subsequently, immunological and molecular signatures, vascular health parameters, and lifestyle factors were assessed, and a comprehensive bioinformatics analysis was conducted to identify biomarkers for predicting subclinical atherosclerosis. The present study was performed in 79 healthy participants (male: n = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD). Participants were categorized according to subclinical atherosclerotic plaque (SAP) status by ultrasound of the carotids. This was followed by a comprehensive analysis using T-cell phenotyping, serum protein signature and gene expression analysis, vascular assessment, analysis of physical activity and capacity as well as food intake. Percentage of CD4⁺-naïve T-cells are the variable with the strongest negative association with the plaque group. Among the top 10 variables, CD4−CD8− lymphocytes are also negatively associated with SAP. In contrast, CD8+ CM T-cells were found positively associated with SAP. LaminB1, tumor protein 53 and systolic blood pressure, central systolic blood pressure, vascular age, osteopontin, and CD4⁺ CM T-cells were also positively associated with SAP. Despite a rather homogeneous cohort of elderly participants with high cardiorespiratory fitness, we have associated various cellular and molecular signatures with the presence of SAP. Significant associations with SAP were shown by known markers of immunosenescence. These results underline the relevance of immunological biomarkers in the detection of subclinical atherosclerosis. Not applicable.

This study investigated elite German athletes to (1) assess their serum 25(OH)D levels and the prevalence of insufficiency, (2) identify key factors influencing serum 25(OH)D levels, and (3) analyze the association between serum 25(OH)D levels and handgrip strength. In this cross-sectional study, a total of 474 athletes (231 female), aged 13–39 years (mean 19.3 years), from ten Olympic disciplines were included. Serum 25(OH)D levels were analyzed via liquid chromatography–mass spectrometry, and 17 single nucleotide polymorphisms (SNPs) related to vitamin D metabolism were determined using leukocyte DNA. Grip strength was measured unimanually using a hand-held dynamometer. Multiple linear regressions were used to analyze the influence of SNPs, age, sex, season (summer vs. winter), and discipline (indoor vs. outdoor) on 25(OH)D status. Linear regression analyzed the relationship between handgrip strength and serum 25(OH)D levels. In total, 55.5 = 7.46, p < .001; CC Genotype: = 6.23, p = .001). Age (all p < .01) and discipline (indoor vs. outdoor; all p < .05) also influenced serum 25(OH)D levels. Furthermore, serum 25(OH)D was positively associated with handgrip strength ( = 0.01, p < .001). A high prevalence of insufficient 25(OH)D levels (< 30 ng/mL, < 75 nmol/L) was observed. We identified certain genetic variants as well as age and discipline as predictors of serum 25(OH)D levels. This knowledge may guide individualized diagnostic, nutritional, and supplementation strategies.

BACKGROUND:The recently identified swine inflammation and necrosis syndrome (SINS) affects tail, ears, teats, coronary bands, claws and heels of affected individuals. The primarily endogenous syndrome is based on vasculitis, thrombosis, and intimal proliferation, involving defence cells, interleukins, chemokines, and acute phase proteins and accompanied by alterations in clinical chemistry, metabolome, and liver transcriptome. The complexity of metabolic alterations and the influence of the boar led to hypothesize a polygenic architecture of SINS. This should be investigated by a transcriptome study. For this purpose, the three to five least affected (SINS-low) and most SINS affected (SINS-high) 3d-old piglets, each of three boars, a relatively SINS stable Duroc boar (DU), a relatively stable Pietrain boar (PI+) and a highly susceptible Pietrain boar (PI-) were selected from 27 litters of mixed semen to minimize environmental effects. RESULTS:A genome-wide expression experiment revealed a huge set of differentially expressed genes that are involved in vasculitis, inflammation and necrosis, keratinization and erythrocyte epitopes. Among them were CRP, GYPA, S100A12, and LIPK. The results confirm and complement previous studies to this topic. CONCLUSIONS:The results confirm the outstanding importance of defence in the context of SINS. At the same time, for the first time, there is evidence for a direct involvement of the keratinisation capacity of the skin and various epitopes of the erythrocyte membrane, which seem to be associated with the severity of SINS. These genes could serve to clarify the pathogenesis of the syndrome and to develop diagnostic tools in future studies.

Mushrooms, the fruiting bodies of edible fungi, are widely used as food for humans. However, their potential, as well as that of fungal mycelia, as feed components for poultry is less acknowledged. Recent studies have shown that feeding the vegetative mycelium of Pleurotus sapidus does not affect growth performance or nutrient digestibility and causes only minimal changes in the cecal microbiota structure, liver transcriptome, and plasma metabolome of broilers. The present study aimed to comprehensively investigate the effects of feeding the fruiting bodies of P. sapidus on performance metrics, ileal nutrient digestibility, cecal microbiota composition, cecal integrity, liver transcriptome, and the expression of genes involved in protein turnover in breast muscle of broilers. A total of 72 male, 1-day-old Cobb 500 broilers were randomly assigned to three groups and fed three distinct diets containing either 0 g (PSA-F0), 25 g (PSA-F25), or 50 g (PSA-F50) of freeze-dried P. sapidus fruiting bodies per kg diet in a 35-day, three-phase feeding regimen. Final body weights and weight gain during the finisher and the whole period were significantly lower in groups PSA-F50 and PSA-F25 compared to group PSA-F0 (P < 0.05). Feed intake during the finisher and the whole period tended to be lower in groups PSA-F50 and PSA-F25 compared to group PSA-F0 (P < 0.1). Average daily apparently digested amounts of most indispensable amino acids were lower in group PSA-F50 than in group PSA-F0 (P < 0.05). Cecal microbial α-diversity indicators (Chao1 and Richness) were significantly higher in the PSA-F50 group compared to the PSA-F0 group (P < 0.05), whereas β-diversity indicators were similar between groups. Taxonomic analysis showed a higher abundance of the class Bacilli and the species unknown_Erysipelatoclostridium and a lower abundance of the class Clostridia in the PSA-F50 group compared to the PSA-F0 group (P < 0.05). Concentrations of total and individual short-chain fatty acids, including acetic acid and propionic acid, in the cecal digesta were lower in the PSA-F50 group compared to the PSA-F0 group (P < 0.05). A total of 66 differentially expressed transcripts were identified in the liver between PSA-F50 and PSA-F0 groups based on filter criteria (FC > 1.3 or FC < -1.3, P < 0.05). The mRNA levels of genes involved in critical pathways such as protein synthesis and degradation—including the mammalian target of rapamycin pathway, myogenesis, the ubiquitin-proteasome system, autophagy-lysosomal pathway, and GCN2/eIF2α pathway—did not vary across the groups. Plasma lipopolysaccharide concentration was similar across all groups. The mRNA levels of CLDN3, MUC2, and MUC5AC were elevated in the PSA-F50 group compared to the PSA-F0 group (P < 0.05), while mRNA levels of CLDN5, OCLN, MUC13, and several pro-inflammatory genes in cecal mucosa remained unchanged across groups. The observed impairment in growth performance suggests that P. sapidus fruiting bodies cannot be recommended as dietary components for broilers at the tested doses. Considering the higher β-glucan content of fruiting bodies compared to vegetative mycelia, the negative effects observed on broiler performance may be associated with their β-glucan content.

Despite the existence of a number of studies investigating the effect of insect meal on the growth performance of broilers, knowledge about the metabolic effects of insect meal in broilers is still scarce. Thus, the present study investigated the effect of partial replacement of soybean meal with Hermetia illucens (HI) larvae meal on the liver transcriptome, the plasma metabolome and the cecal microbiota in broilers. For the study, 72 male one-day-old Cobb 500 broilers were divided into three groups and fed three different diets with either 0% (HI0), 7.5% (HI7.5) or 15% (HI15) defatted HI meal for 35 d. Each group consisted of 6 cages (replicates) with 4 broilers/cage. While body weight (BW) gain, feed intake, and feed:gain ratio did not differ between groups, breast muscle weight, carcass yield and apparent ileal digestibility (AID) of 5 amino acids were higher in group HI15 than in group HI0 (P < 0.05). Indicators of α-diversity (Chao1 and Observed) in the cecal digesta were higher in groups HI15 and HI7.5 than in group HI0 (P < 0.05). The abundance of 5 families and 18 genera, all of which belonged to the Firmicutes phylum, in the cecal digesta differed among groups (P < 0.05). Concentrations of butyric acid, valeric acid and isobutyric acid in the cecal digesta were lower in group HI15 than in the other two groups (P < 0.05), whereas those of total and other short-chain fatty acids were not different between groups. Liver transcriptomics revealed a total of 70 and 61 differentially expressed transcripts between groups HI15 vs. HI0 and between groups HI7.5 vs HI0, respectively, (P < 0.05). Targeted metabolomics identified 138 metabolites, most of which were triglyceride species, being different between the three groups (FDR < 0.05). According to this study, dietary inclusion of HI larvae meal has no detrimental impact but increases breast muscle weight and carcass weight in broilers suggesting that HI larvae meal can be recommended as a sustainable alternative protein source for broilers.

Submerged cultivation using low-value agro-industrial side streams allows large-scale and efficient production of fungal mycelia, which has a high nutritional value. As the dietary properties of fungal mycelia in poultry are largely unknown, the present study aimed to investigate the effect of feeding a Pleurotus sapidus (PSA) mycelium as a feed supplement on growth performance, composition of the cecal microbiota and several physiological traits including gut integrity, nutrient digestibility, liver lipids, liver transcriptome and plasma metabolome in broilers. 72 male, 1-day-old Cobb 500 broilers were randomly assigned to three different groups and fed three different adequate diets containing either 0% (PSA-0), 2.5% (PSA-2.5) and 5% (PSA-5.0) P. sapidus mycelium in a three-phase feeding system for 35 days. Each group consisted of 6 cages (replicates) with 4 broilers/cage. Body weight gain, feed intake and feed:gain ratio and apparent ileal digestibility of crude protein, ether extract and amino acids were not different between groups. Metagenomic analysis of the cecal microbiota revealed no differences between groups, except that one α-diversity metric (Shannon index) and the abundance of two low-abundance bacterial taxa (Clostridia UCG 014, Eubacteriales) differed between groups (P < 0.05). Concentrations of total and individual short-chain fatty acids in the cecal digesta and concentrations of plasma lipopolysaccharide and mRNA levels of proinflammatory genes, tight-junction proteins, and mucins in the cecum mucosa did not differ between groups. None of the plasma metabolites analyzed using targeted-metabolomics differed across the groups. Hepatic transcript profiling revealed a total of 144 transcripts to be differentially expressed between group PSA-5.0 and group PSA-0 but none of these genes was regulated greater 2-fold. Considering either the lack of effects or the very weak effects of feeding the P. sapidus mycelium in the broilers it can be concluded that inclusion of a sustainably produced fungal mycelium in broiler diets at the expense of other feed components has no negative consequences on broilers´ performance and metabolism.

Background : Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (Tregs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with Tregs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures. Methods : A cross-sectional study was performed in 79 participants (male: n = 50; age = 63.6 +/- 3.7 years; body mass index = 24.9 +/- 3.1 kg/m 2 ; mean +/- SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of Tregs and their subtypes (resting (rTregs) and effector/memory (mTregs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters. Results : SAP was detected in a total of 29 participants. The participants with plaque were older (64.8 +/- 3.6 years vs. 62.9 +/- 3.5 years) and had higher peripheral systolic blood pressure (133.8 +/- 14.7 mmHg vs . 125.8 +/- 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rTregs (28.8% +/- 10.7% vs . 34.6% +/- 10.7%) and a higher percentage of mTregs (40.3% +/- 14.7% vs . 30.0% +/- 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01 - 1.42)) and mTregs (OR = 1.05 (95%CI: 1.02 - 1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake ( fi = 0.441), low -density lipoprotein (LDL) ( fi = - 0.096), and SAP ( fi = 6.733) with mTregs and LDL ( fi = 0.104) with rTregs. Conclusion : While at an early stage of SAP, the total proportion of Tregs gives no indication of vascular changes, this is indicated by a shift in the Treg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle -based preventive measures at an early stage, which may have a protective effect against disease progression.

Background The use of conventional two-dimensional (2D) culture of the porcine intestinal epithelial cell (IEC) line IPEC-J2 in animal nutrition research has the disadvantage that IEC function is studied under unphysiological conditions, which limits the ability of transferring knowledge to the in vivo-situation. Thus, the aim of the present study was to establish a more convincing and meaningful three-dimensional (3D) culture of IPEC-J2 cells, which allows to study cell function in a more tissue-like environment, and to compare the effect of the endoplasmic reticulum (ER) stress inducer tunicamycin (TM) on ER stress indicators and the expression of tight junction proteins (TJP), inflammatory and apoptosis-related genes and the modulatory role of 1,25-dihydroxy-vitamin D-3 (1,25D(3)) on these parameters in 2D and 3D cultures of IPEC-J2 cells. Results A published protocol for 3D culture of Caco-2 cells was successfully adopted to IPEC-J2 cells as evident from fully differentiated 3D IPEC-J2 spheroids showing the characteristic spherical architecture with a single layer of IPEC-J2 cells surrounding a central lumen. Treatment of 2D IPEC-J2 cells and 3D IPEC-J2 spheroids with TM for 24 h markedly increased mRNA and/or protein levels of the ER stress target genes, heat shock protein family A (Hsp70) member 5 (HSPA5) and DNA damage inducible transcript 3 (DDIT3), whereas co-treatment with TM and 1,25D(3) did not mitigate TM-induced ER stress in IPEC-J2 cells in the 2D and the 3D cell culture. In contrast, TM-induced expression of pro-inflammatory [interleukin-6 (IL6), IL8] and pro-apoptotic genes [BCL2 associated X, apoptosis regulator (BAX), caspase 3 (CASP3), CASP8] and genes encoding TJP [TJP1, claudin 1 (CLDN1), CLDN3, occludin (OCLN), cadherin 1 (CDH1), junctional adhesion molecule 1 (JAM1)] was reduced by co-treatment with TM and 1,25D(3) in 3D IPEC-J2 spheroids but not in the 2D cell culture. Conclusions The effect of 1,25D(3) in the IPEC-J2 cell culture is dependent on the culture model applied. While 1,25D(3) does not inhibit TM-induced expression of genes involved in inflammation, apoptosis and TJP in conventional 2D cultures of IPEC-J2 cells, TM-induced expression of these genes is abrogated by 1,25D(3) in the more meaningful 3D IPEC-J2 cell culture model.

Background: Palm oil (PO) is the most widely utilized plant oil for food production. Owing to the great ecologic problems associated with PO production, sustainably produced fats, such as insect fat, might be a suitable alternative. Objectives: The hypothesis was tested that fat from Hermetia illucens larvae (HF) compared with PO and soybean oil (SO) has no adverse effects on hepatic lipid metabolism, plasma metabolome, and cecal microbiome in obese Zucker rats . Methods: Thirty male obese Zucker rats were randomly assigned to 3 groups (SO, PO, HF; n = 10 rats/group) and fed 3 different semisynthetic diets containing either SO, PO, or HF as the main fat source for 4 wk. The effects were evaluated by measurement of liver and plasma lipid concentrations, liver transcriptomics, targeted plasma metabolomics, and cecal microbiomics. Results: Supplementation of HF reduced hepatic triglyceride concentration and messenger ribonucleic acid concentrations of selected genes involved in fatty acid and triglyceride synthesis in comparison to PO (P < 0.05). Pairwise comparison of the Simpson index and Jaccard index showed a higher cecal microbial alpha- and beta-diversity in rats fed the HF diet than in rats fed the PO diet (P = 0.015 and P = 0.027), but no difference between rats fed the diets with SO or PO. Taxonomic analysis of the cecal microbial community revealed a lower abundance of Clostridium_sensu_stricto_1 and a higher abundance of Blautia, Mucispirillum, Anaerotruncus, Harryflintia, and Peptococcus in rats supplemented with HF than in rats supplemented with PO (P < 0.05). Conclusions: HF, compared with PO, has liver lipid-lowering effects in obese Zucker rats, which may be caused by a shift in the gut microbial community. Thus, HF might serve as a sustainably produced fat alternative to PO for food production.