Search Results (29)

Obesity is a chronic metabolic condition characterized by low-grade inflammation and oxidative imbalance and is strongly associated with impaired male reproductive function. This study investigated whether prebiotic–probiotic supplementation could prevent or attenuate high-fat diet (HFD)-induced metabolic inflammation-associated reproductive toxicity in male rats. Animals were assigned to four groups: normal diet (ND), HFD, HFD with concurrent prebiotic–probiotic supplementation from the onset of feeding (P-HFD), and HFD followed by supplementation initiated after 5 weeks (HFD-P). Evaluations included body and reproductive organ weights, sperm parameters, testicular histopathology, reproductive hormones, oxidative stress and inflammatory biomarkers, and gut microbiome composition. HFD feeding induced pronounced reproductive impairment, evidenced by reduced relative testicular weight, disrupted spermatogenesis, decreased LH levels, elevated TNF-α, a paradoxical increase in intratesticular testosterone despite reduced LH, and marked gut dysbiosis, characterized by shifts in microbial community structure along with reduced microbial diversity. Prebiotic–probiotic supplementation did not fully restore microbial richness or return the microbiota to an ND-like configuration; however, concurrent supplementation induced more pronounced taxonomic restructuring than delayed supplementation. While P-HFD did not show significant improvements in sperm parameters or LH, it exhibited clear histological preservation of testicular structure, reduced TNF-α, and partial normalization of testosterone, indicating attenuation of HFD-induced inflammation-associated testicular toxicity rather than complete functional recovery. In contrast, delayed supplementation produced no meaningful improvement in reproductive, hormonal, or microbiome-related outcomes and, in several respects, more pronounced testicular inflammation and structural degeneration than HFD alone. Collectively, these findings indicate that intervention timing is critical: concurrent administration conferred greater structural and anti-inflammatory protection against HFD-induced testicular damage, whereas delayed intervention was insufficient—or even counterproductive—once testicular injury was established. This timing-dependent response highlights the potential of microbiota-targeted strategies as supportive, timing-sensitive approaches for mitigating obesity-related male reproductive toxicity. Full article

Background/Objectives: Numerous studies have investigated the responses of the gastrointestinal tract to tastants, particularly in specialized enteroendocrine and other chemosensory cells. However, many of these investigations used various taste stimuli often at high concentrations or relied on immortalized cell lines or heterogeneous cell populations, which can limit their physiological relevance and reproducibility. To establish a stable, physiologically representative model system for consistently investigating gut epithelial responses to tastants, our study developed 3D murine intestinal organoids (MIOs). Methods: Murine intestinal organoids were generated from isolated intestinal crypts and cultured under defined conditions to maintain epithelial differentiation. Organoids were stimulated with selected nutrients and tastants, and downstream signaling responses were assessed using hormone secretion assays. Results: The 3D MIO culture system was successfully established, providing a robust in vitro platform for studying extraoral bitter sensing and release of the enteroendocrine hormone cholecystokinin. Moreover, 5 mM denatonium benzoate and 30 mM L-glutamic acid specifically induced cholecystokinin secretion in MIOs, whereas other bitter or non-bitter stimuli did not. Conclusions: Murine intestinal organoids provide a stable model for studying nutrient- and tastant-evoked signaling in the gut. This approach enables precise investigation of underlying mechanisms and may advance our understanding of gut chemosensation and metabolic regulation. Full article

This study aimed to investigate the effects of dietary Herba Epimedii Folium (HEF) supplementation on semen quality, reproductive hormones, immune parameters, gut microbiota, and seminal plasma metabolites in aged boars, and to evaluate its potential for extending their reproductive lifespan. A total of 18 Bama boars (approximately 3 years of age) were randomly assigned to three groups (n = 6 per group). The control group received a basal diet, while the treatment groups were fed the basal diet supplemented with 3 g/kg or 5 g/kg of HEF for 8 weeks. The results showed that adding HEF to the diet of aged boars increased the motility and concentration of their sperm and reduced the proportion of abnormal sperm. Treatment with 3 g/kg HEF increased serum LH and IgG levels, whereas the 5 g/kg dose elevated IgA levels in both serum and seminal plasma, as well as IgG levels in seminal plasma. Furthermore, 16S rRNA sequencing revealed that dietary HEF supplementation reduced the relative abundance of Streptococcus and Oscillospiraceae UCG-002 in the gut of aged boars. PICRUSt2 analysis predicted that pathways involved in lysine biosynthesis, arginine and proline metabolism, glycine, serine and threonine metabolism, and amino acid-related enzymes were enriched in the HEF treatment group. Semen metabolite profiling showed that the HEF treatment enriched several key metabolites, including 5-hydroxytryptophan, acetylcarnitine, tretinoin, methyltestosterone, prostaglandin A3, and prostaglandin B2. Spearman correlation analysis revealed a negative association between Streptococcus abundance and sperm motility, whereas acetylcarnitine, 5-hydroxytryptophan, and prostaglandin A3 were positively associated with motility. Furthermore, 5-hydroxytryptophan levels were positively linked to both sperm concentration and serum LH. In summary, our study demonstrates that Epimedii Folium may enhance the semen quality of aged Bama boars by improving the intestinal microbiota and the metabolic profile of seminal plasma. These findings may offer a theoretical basis for optimizing reproduction and conserving germplasm resources in aged Bama miniature pigs. Full article

Long-duration space missions expose astronauts to galactic cosmic radiation (GCR), a complex spectrum of high-charge, high-energy (HZE) ions that pose significant risks of chronic tissue injury. To model these effects, we examined intestinal outcomes in wild-type mice 5 months after low-dose (50 cGy) 33-ion mixed-field GCR simulation (GCRsim). GCRsim induced sustained DNA double-strand breaks (DSBs) and oxidative stress, as shown by elevated γH2AX foci and 4-HNE staining. Intestinal epithelial cells (IECs) exhibited pronounced senescence, marked by increased SA-β-gal activity, p16 upregulation, LaminB1 loss, and induction of senescence-associated secretory phenotype (SASP) cytokines (Cxcl10, IL-6, IL-1β, Icam1). GCRsim also elevated circulating LINE-1 DNA and reduced expression of DNA-degrading nucleases (DNase2, TREX1), indicating impaired extracellular DNA clearance. Targeted molecular study revealed persistent activation of the cGAS–STING pathway, with elevated cGAS, STING, pTBK1, pIKKα/β, and nuclear pIRF3, pIRF7, and p65, consistent with chronic innate immune signaling. Functionally, GCRsim altered nutrient absorption gene expression—upregulating glucose transporters (Slc2a2, Slc2a5, Slc5a1) and gut hormones (Cck, Gip), while downregulating cholesterol/fat transporters (Npc1, Npc1l1). Biochemical markers supported intestinal injury, with decreased serum citrulline and increased intestinal fatty acid-binding protein (I-FABP), indicating barrier compromise. Collectively, these findings demonstrate that GCRsim drives sustained intestinal dysfunction, highlighting the need for countermeasures to protect GI health during deep-space missions. Full article

This research investigated the impact of corn–soybean meal-based fermented feed on the growth performance, pork quality, and fatty acid profiles of lean-type finishing pigs. A total of 80 lean-type growing DLY (Duroc × Landrace–Yorkshire) pigs were randomly assigned to 2 groups, with 5 replicates of 8 pigs per pen. The pigs in control group (CON group) were fed a basal diet, while the pigs in fermented feed group (FF group) were fed a diet supplemented with 10% fermented feed. The experimental period lasted 70 days. Results exhibited that pigs in FF group had a significant increase in final body weight and average daily gain (ADG) (p < 0.05) and had a significant decrease in the feed-to-gain ratio (F/G) (p < 0.05). The FF group also exhibited significant promotion in muscle intramuscular fat content, marbling score, and meat color and significantly reduced the meat shear force and drip loss (p < 0.05). Serum analysis indicated that fermented feed significantly elevated blood glucose, total cholesterol, triglyceride levels, and serum hormones such as insulin, leptin, and IGF-1 (p < 0.05). Additionally, fermented feed significantly elevated the levels of polyunsaturated fatty acids (PUFAs) and monounsaturated fatty acids (MUFAs), whereas it decreased the saturated fatty acids (SFAs) contents (p < 0.05). The fermented feed also significantly enhanced pork nutritional values (p < 0.05). The fermented feed increased the expression of IGF-1, SREBP1c, PDE3, PPARγ, SCD5, and FAT/CD36 mRNA (p < 0.05). Furthermore, microbial 16S rDNA analysis uncovered that FF supplementation significantly reduced the Campilobacterota phylum abundance, while increasing the genus abundances of Clostridium_sensu_stricto, norank_f_Oscillospiraceae, unclassified_c_Clostridia, and V9D2013 (p < 0.05). In summary, the results indicated that the microbial fermented feed exhibited the regulation effects on pork quality and nutritional values of lean-type pigs through regulating lipid metabolism and gut microbial composition. Full article

Despite the known impacts of weaning on animal health, the underlying molecular mechanisms remain unclear, particularly how psychological and nutritional stress differentially affect gut health and immune function over time. This study hypothesized that early weaning exerts distinct short- and long-term effects on lamb stress physiology, immunity, and gut health, mediated by specific molecular pathways. Twelve pairs of full-sibling male Hu sheep lambs were assigned to control (CON) or early-weaned (EW) groups. Plasma stress/immune markers were dynamically monitored, and intestinal morphology, antioxidant capacity, apoptosis, and transcriptomic profiles were analyzed at 5 and 28 days post-weaning. Early weaning triggered transient psychological stress, elevating hypothalamic–pituitary–adrenal (HPA) axis hormones (cortisol, catecholamines) and inflammatory cytokines (TNF-α) within 1 day (p < 0.05); however, stress responses were transient and recovered by 7 days post-weaning. Sustained intestinal remodeling was observed in EW lambs, featuring reduced ileal villus height, increased crypt depth (p < 0.05), and oxidative damage (MDA levels doubled vs. CON; p < 0.01). Compensatory epithelial adaptation included increased crypt depth but paradoxically reduced villus tip apoptosis. The transcriptome analysis revealed significant changes in gene expression related to immune function, fat digestion, and metabolism. Key DEGs included APOA4, linked to lipid transport adaptation; NOS2, associated with nitric oxide-mediated immune–metabolic crosstalk; and mitochondrial gene COX1, reflecting energy metabolism dysregulation. Protein–protein interaction analysis revealed NOS2 as a hub gene interacting with IDO1 and CXCL11, connecting oxidative stress to immune cell recruitment. Early weaning exerts minimal lasting psychological stress but drives persistent gut dysfunction through transcriptome-mediated changes in metabolic and immune pathways, highlighting key genes such as APOA4, NOS2, and COX1 as potential regulators of these effects. Full article

Background/Objectives: Urolithin A (UA), a gut-derived metabolite of ellagitannins or ellagic acid, has recently gained attention for its potential benefits to brain health. The present research aimed to assess the antidepressant-like properties of UA in both in vitro and in vivo models and explored the molecular mechanisms underlying these effects. Methods: We investigated the antidepressant effects and mechanisms of UA in a model of corticosterone-induced damage to PC12 cells and in a model of chronic socially frustrating stress. Results: Our results demonstrate that UA treatment (5 and 10 μM) significantly alleviated cellular damage and inflammation in corticosterone (CORT)-treated PC12 cells. Furthermore, UA administration (50 and 100 mg/kg) significantly reduced immobility time in the mouse tail suspension test (TST) and forced swim test (FST), indicating its antidepressant-like activity. Additionally, treatment with UA led to the activation of the cAMP response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) signaling cascade and triggered the activation of adenosine monophosphate-activated protein kinase (AMPK) during these processes. Importantly, pretreatment with AMPK-specific inhibitor Compound C abolished UA’s cytoprotective effects in PC12 cells, as well as its behavioral efficacy in the FST and TST, and its neurotrophic effects, highlighting the critical role of AMPK activation in mediating these effects. Furthermore, in the chronic social defeat stress (CSDS) mouse model, UA treatment (50 and 100 mg/kg) significantly alleviated depression-like behaviors, including reduced sucrose preference in the sucrose preference test, increased social avoidance behavior in the social interaction test, and anxiety-like behaviors, including diminished exploration, in the elevated plus maze test, suggesting the antidepressant-like and anxiolytic-like activities of UA. Moreover, UA treatment reversed elevated serum stress hormone levels, hippocampal inflammation, and the decreased AMPK/CREB/BDNF signaling pathway in the hippocampus of CSDS mice. Conclusions: Together, these results provide compelling evidence for UA as a viable dietary supplement or therapeutic option for managing depression. Full article

The early-stage feeding of calves significantly impacts their lifelong productive performance. During this period, the calves’ digestive tracts are in a dynamic state of development, making nutritional regulation a key factor in optimizing their growth potential. This research investigated the influence of mannan-rich fraction (MRF) supplementation on pre-weaning calves. Sixty healthy Holstein calves were randomly divided into a control group and three MRF-supplemented groups (seven males and eight females per group) with low (L-MRF, 2.5 g/calf per day), medium (M-MRF, 5 g/calf per day), and high (H-MRF, 10 g/calf per day) doses. Growth performance, serum biochemical indicators, organ indices, intestinal morphology, and short-chain fatty acid (SCFA) concentrations were measured over a 42-day experiment. Compared with the control group, the M-MRF group had 4.9% higher overall body weight, body length, and starter intake, alongside a reduced diarrhea incidence by 4.6%. At day 14, MRF-supplemented groups exhibited significantly lower Interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) levels, along with significantly higher Interleukin-12 (IL-12), growth hormone (GH), and Immunoglobulin G (IgG) levels. By day 42, IL-6 and Interleukin-1β (IL-1β) levels were also significantly decreased. Additionally, the lung and liver indices were higher and villus height was greater in both the jejunum and colon with MRF supplementation. In terms of SCFAs, the acetate level in the jejunum and the butyrate level in the colon were significantly higher in the MRF-supplemented calves. Both acetate in the jejunum and butyrate in the colon showed a significantly positive correlation with growth performance. Taken together, these findings suggest that MRF supplementation (particularly at 5 g/day) supports calf growth, gut health, and immunity, making it a promising nutritional strategy for pre-weaning calves. Full article

Background/Objectives: Alzheimer’s disease (AD), a leading cause of dementia, lacks effective long-term treatments. Current therapies offer temporary relief or fail to halt its progression and are often inaccessible due to cost. AD involves multiple pathological processes, including amyloid beta (Aβ) deposition, insulin resistance, tau protein hyperphosphorylation, and systemic inflammation accelerated by gut microbiota dysbiosis originating from a leaky gut. Given this context, exploring alternative therapeutic interventions capable of addressing the multifaceted components of AD etiology is essential. Methods: This study suggests D-Pinitol (DPIN) as a potential treatment modifier for AD. DPIN, derived from carob pods, demonstrates insulin-sensitizing, tau hyperphosphorylation inhibition, and antioxidant properties. To test this hypothesis, we studied whether chronic oral administration of DPIN (200 mg/kg/day) could reverse the AD-like disease progression in the 5×FAD mice. Results: Results showed that treatment of 5×FAD mice with DPIN improved cognition, reduced hippocampal Aβ and hyperphosphorylated tau levels, increased insulin-degrading enzyme (IDE) expression, enhanced pro-cognitive hormone circulation (such as ghrelin and leptin), and normalized the PI3K/Akt insulin pathway. This enhancement may be mediated through the modulation of cyclin-dependent kinase 5 (CDK5). DPIN also protected the gut barrier and microbiota, reducing the pro-inflammatory impact of the leaky gut observed in 5×FAD mice. DPIN reduced bacterial lipopolysaccharide (LPS) and LPS-associated inflammation, as well as restored intestinal proteins such as Claudin-3. This effect was associated with a modulation of gut microbiota towards a more balanced bacterial composition. Conclusions: These findings underscore DPIN’s promise in mitigating cognitive decline in the early AD stages, positioning it as a potential disease modifier. Full article

Lighting is crucial for the development of broilers as it affects their growth performance, oxidative stress, and overall health. This study investigates the impact of full-spectrum light, infrared light, and LED white light exposure on the growth performance, oxidative stress markers, and cecal microbiota of medium-growth yellow-feathered broilers. A total of 216 medium-growth yellow-feathered chicks (Yuhuang No. 5), five days old, were randomly divided into three groups: 72 chicks in each group, with three replicates of 24 chicks. The birds were raised under different lighting conditions, including LED infrared light (II), full-spectrum therapy light (FB), and LED white light (CG) until day 87. This experiment comprised the early growth phase and measured critical hormones such as Melatonin (Mel), Growth Hormone (GH), and Growth Hormone Releasing Hormone (GHRH), as well as Malondialdehyde (MDA), Superoxide Dismutase (SOD), and Catalase (CAT). Additionally, this study examined the differences in microbiota diversity and composition. The results demonstrated that LED infrared and full-spectrum light exposure significantly (p < 0.05) increased broiler body weight. Particularly, full-spectrum light was effective in comb redness and reducing final comb length and oxidative stress. Furthermore, full-spectrum light improved microbial prosperity and diversity compared with the other lighting conditions. Overall, the findings suggest that full-spectrum lighting is more beneficial for broiler growth, reducing oxidative stress, and promoting gut health compared with LED infrared lighting. These insights can be applied to optimizing broiler farming practices, thereby improving productivity and animal welfare. Full article

Minerals constitute only 5% of the typical human diet but are vital for health and functionality. Copper, a trace element, is absorbed by the human gut at 30–40% from diets typical of industrialized countries. The liver produces metallothioneins, which store copper. Copper is crucial for mitochondrial respiration, pigmentation, iron transport, antioxidant defense, hormone production, and extracellular matrix biosynthesis. Copper deficiency, often caused by mutations in the ATP7A gene, results in Menkes disease, an X-linked recessive disorder. On the contrary, Wilson disease is characterized by toxic copper accumulation. Cuproptosis, a unique form of cell death regulated by copper, is a subtype of necrosis induced by enhanced mitochondrial metabolism and intracellular copper accumulation. This process can reduce the malignant potential of tumor cells by inhibiting glucose metabolism. Therapeutically, copper and its complexes have shown efficacy in malignancy treatments. The disruption of copper homeostasis and excessive cuproplasia are significant in colorectal cancer development and metastasis. Therefore, manipulating copper status presents a potential therapeutic target for colorectal cancer, using copper chelators to inhibit copper formation or copper ion carriers to promote cuproptosis. This review highlights the role of copper in human physiology and pathology, emphasizing its impact on colorectal cancer and potential therapeutic strategies. Future AI-based approaches are anticipated to accelerate the development of new compounds targeting cuproptosis and copper disruption in colorectal cancer. Full article

Nanoplastics (NPs) cause serious contamination of drinking water and potential damage to human health. This study aimed to investigate the effects of NPs with different particle sizes and concentrations on the reproductive function of male mice. In this study, free drinking water exposure was used to expose male BALB/C mice to PS-NPs (20 nm, 200 nm, and 1000 nm) at 0.1 mg/L, 1 mg/L, and 5 mg/L for 4 months. The male reproductive function of the mice was assessed after NPs exposure, and fecal and blood samples were collected for macrogenomics and metabolomics. The results showed that PS-NPs resulted in mice with reduced testicular organ coefficients, decreased sperm quality, altered testicular tissue structure, disturbed sex hormone levels, and abnormal levels of inflammatory factors and oxidative stress. Furthermore, this study found that NP exposure affected the alteration of gut communities and metabolic pathways related to male reproduction, such as Clostridium and glutathione metabolism. Importantly, we found an effect of NP particle size on reproductive function. In the future, more attention should be paid to the smaller particle sizes of NPs. Full article

Previous studies on the early interference of gut microbiota by Bacillus siamensis (B. siamensis) in weaned piglets are rarely reported, and the present trial is a preliminary study. This experiment was conducted to investigate the effects of B. siamensis supplementation on the growth performance, serum biochemistry, immune response, fecal short-chain fatty acids and microbiota of weaned piglets. Sixty weaned piglets were randomly divided into a control group (CON) and a B. siamensis group (BS), which were fed a basal diet and the basal diet supplemented with 5 × 10¹⁰ CFU B. siamensis per kg, respectively. Each group had 3 replicates and 10 piglets per replicate. The trial lasted for 28 days. The results showed that B. siamensis significantly increased the serum growth hormone (GH) and insulin-like growth factor (IGF) in piglets. Compared with the CON group, the levels of serum immunoglobulin and inflammatory factors in the BS group were significantly improved. In addition, the serum concentrations of zonulin and endotoxin (ET) in the BS group were lower. The dietary addition of B. siamensis significantly increased fecal short-chain fatty acid (SCFA) levels in piglets. Notably, B. siamensis improved the microbial composition by increasing beneficial genera, including Weissella, Lachnospiraceae_NK4A136_group and Bifidobacterium, and decreasing pathogenic genera, including Pantoea, Fusobacterium and Gemella, in piglet feces. Correlation analysis showed that the benefits of dietary B. siamensis supplementation were closely related to its improved microbial composition. In summary, the addition of B. siamensis can improve the immunity function, inflammatory response, gut permeability and SCFA levels of weaned piglets, which may be achieved through the improvement of their microbiota. Full article

Excess body weight constitutes one of the major health challenges for societies and healthcare systems worldwide. Besides the type of diet, calorie intake and the lack of physical exercise, recent data have highlighted a possible association between endocrine-disrupting chemicals (EDCs), such as bisphenol A, phthalates and their analogs, and obesity. EDCs represent a heterogeneous group of chemicals that may influence the hormonal regulation of body mass and adipose tissue morphology. Based on the available data from mechanistic, animal and epidemiological studies including meta-analyses, the weight of evidence points towards the contribution of EDCs to the development of obesity, associated disorders and obesity-related adipose tissue dysfunction by (1) impacting adipogenesis; (2) modulating epigenetic pathways during development, enhancing susceptibility to obesity; (3) influencing neuroendocrine signals responsible for appetite and satiety; (4) promoting a proinflammatory milieu in adipose tissue and inducing a state of chronic subclinical inflammation; (5) dysregulating gut microbiome and immune homeostasis; and (6) inducing dysfunction in thermogenic adipose tissue. Critical periods of exposure to obesogenic EDCs are the prenatal, neonatal, pubertal and reproductive periods. Interestingly, EDCs even at low doses may promote epigenetic transgenerational inheritance of adult obesity in subsequent generations. The aim of this review is to summarize the available evidence on the role of obesogenic EDCs, specifically BPA and phthalate plasticizers, in the development of obesity, taking into account in vitro, animal and epidemiologic studies; discuss mechanisms linking EDCs to obesity; analyze the effects of EDCs on obesity in critical chronic periods of exposure; and present interesting perspectives, challenges and preventive measures in this research area. Full article

This paper describes cases of urolithiasis in fattening pigs on two farms (A and B). Bladder rupture due to urethral obstruction with calculi was the principal finding during the necropsy of the pigs. An in-depth diagnostic examination was performed to elucidate possible pathophysiological mechanisms, namely Fourier-transform infrared spectrophotometry (FT-IR) analysis of the uroliths, blood analysis (farm A: 5 samples, farm B: 10 samples) for assessing concentrations of minerals, the bone resorption marker cross-linked C-telopeptide of type 1 collagen (CTX), parathyroid hormone (PTH), and vitamin D components, biochemical urinalysis (farm A: 5 samples, farm B: 7 samples), microscopic examination of urinary sediment (Farms A and B: 7 samples each), mineral composition of the feed, and analysis of the drinking water. Calcium carbonate was the main component found in stones from both farms, and calcium carbonate and struvite were the main components found in crystals from farms A and B, respectively. On farm A, urinary calcium excretion and urinary pH were high; on farm B, urinary phosphorus was high and urinary calcium was low with a normal urinary pH. The mineral compositions of the feed and drinking water were similar on both farms and could therefore not explain the difference between the two farms. Disturbances in calcium and phosphorus absorption and homeostasis might have been involved in these problems. Further research should focus on the calcium, phosphorus, and vitamin D levels in the feed and take into account other factors, such as the absorption and excretion of minerals due to gut and urinary microbiota. Full article