Intestinal diseases are highly prevalent, affecting millions worldwide and significantly contributing to global morbidity. The treatment of complex disorders, such as inflammatory bowel disease (IBD) and colorectal cancer (CRC), remains challenging due to multifactorial etiologies, diverse patient responses, and the limitations of current therapeutic strategies. Although the gut microbiota clearly plays a role in regulating the onset of intestinal diseases, few studies have explored the epigenetic factors by which the microbiota contributes to disease development. Here, the latest insights into the molecular mechanisms underlying the bidirectional influence between gut microbiota and epigenetic modifications are discussed, including DNA methylation, histone modifications, non-coding RNAs, and N6-methyladenosine (m⁶A). Importantly, mechanistic studies based on animal models or human cells have demonstrated that the gut microbiota, and other environmental factors, influence targeted gene expression and activate immune pathways through host epigenetic dysregulation, which are closely associated with the development of IBD and CRC. Furthermore, potential microbiome interventions, including probiotics, prebiotics and postbiotics, fecal microbiota transplantation (FMT), dietary modifications, and phage therapy, have been proposed as innovative therapeutic strategies to correct these abnormal epigenetic patterns associated with the diseases. Overall, addressing microbiome dysbiosis and its epigenetic consequences presents a promising frontier in the treatment of intestinal diseases, offering the potential to not only restore microbial balance but also provide more targeted and personalized therapeutic strategies for better patient outcomes.

Endothelial cell (EC) metabolism plays a crucial role in the process of angiogenesis. Intrinsic metabolic events such as glycolysis, fatty acid oxidation, and glutamine metabolism, support secure vascular migration and proliferation, energy and biomass production, as well as redox homeostasis maintenance during vessel formation. Nevertheless, perturbation of EC metabolism instigates vascular dysregulation-associated diseases, especially cancer. In this review, we aim to discuss the metabolic regulation of angiogenesis by EC metabolites and metabolic enzymes, as well as prospect the possible therapeutic opportunities and strategies targeting EC metabolism. In this work, we discuss various aspects of EC metabolism considering normal and diseased vasculature. Of relevance, we highlight that the implications of EC metabolism-targeted intervention (chiefly by metabolic enzymes or metabolites) could be harnessed in orchestrating a spectrum of pathological angiogenesis-associated diseases.

Ulcerative colitis (UC) is often accompanied by intestinal inflammation and disruption of intestinal epithelial structures, which are closely associated with changes in the intestinal microbiota. We previously revealed that Min pigs, a native Chinese breed, are more resistant to dextran sulfate sodium (DSS)-induced colitis than commercial Yorkshire pigs. Characterizing the microbiota in Min pigs would allow identification of the core microbes that confer colitis resistance. By analyzing the microbiota linked to the disease course in Min and Yorkshire pigs, we observed that Bacillus spp. were enriched in Min pigs and positively correlated with pathogen resistance. Using targeted screening, we identified and validated Bacillus siamensis MZ16 from Min pigs as a bacterial species with biofilm formation ability, superior salt and pH tolerance, and antimicrobial characteristics. Subsequently, we administered B. siamensis MZ16 to conventional or microbiota-deficient BALB/c mice with DSS-induced colitis to assess its efficacy in alleviating colitis. B. siamensis MZ16 partially counteracted DSS-induced colitis in conventional mice, but it did not mitigate DSS-induced colitis in microbiota-deficient mice. Further analysis revealed that B. siamensis MZ16 administration improved intestinal ecology and integrity and immunological barrier function in mice. Compared to the DSS-treated mice, mice preadministered B. siamensis MZ16 exhibited improved relative abundance of potentially beneficial microbes ( Lactobacillus , Bacillus , Christensenellaceae R7 , Ruminococcus , Clostridium , and Eubacterium ), reduced relative abundance of pathogenic microbes ( Escherichia-Shigella ), and maintained colonic OCLN and ZO-1 levels and IgA and SIgA levels. Furthermore, B. siamensis MZ16 reduced proinflammatory cytokine levels by reversing NF-κB and MAPK pathway activation in the DSS group. Overall, B. siamensis MZ16 from Min pigs had beneficial effects on a colitis mouse model by enhancing intestinal barrier functions and reducing inflammation in a gut microbiota-dependent manner.

The neural mechanisms underlying novelty detection are not well understood, especially in relation to behavior. Here, we present single-unit responses from the primary auditory cortex (A1) from two monkeys trained to detect deviant tones amid repetitive ones. Results show that monkeys can detect deviant sounds, and there is a strong correlation between late neuronal responses (250-350 ms after deviant onset) and the monkeys' perceptual decisions. The magnitude and timing of both neuronal and behavioral responses are increased by larger frequency differences between the deviant and standard tones and by increasing the number of standard tones preceding the deviant. This suggests that A1 neurons encode novelty detection in behaving monkeys, influenced by stimulus relevance and expectations. This study provides evidence supporting aspects of predictive coding in the sensory cortex.

The intestinal architecture of piglets is vulnerable to disruption during weaning transition and leads to diarrhea, frequently accompanied by inflammation and metabolic disturbances (including amino acid metabolism). Tryptophan (Trp) plays an essential role in orchestrating intestinal immune tolerance through its metabolism via the kynurenine, 5-hydroxytryptamine, or indole pathways, which could be dictated by the gut microbiota either directly or indirectly. Emerging evidence suggests a strong association between piglet diarrhea and Trp metabolism. Here we aim to summarize the intricate balance of microbiota–host crosstalk by analyzing alterations in both the host and microbial pathways of Trp and discuss how Trp metabolism may affect piglet diarrhea. Overall, this review could provide valuable insights to explore effective strategies for managing piglet diarrhea and the related challenges.

Background: Weaning-induced diarrhoea and growth retardation in piglets are associated with impaired intestinal barrier function and decreased levels of colonic short-chain fatty acids (SCFAs). Although SCFA supplementation has been proposed to mitigate these issues, the efficacy and optimal dosage of sodium isobutyrate remain unclear. Results: We investigated the effects of sodium isobutyrate supplementation (500, 1,000, 2,000, and 4,000 mg/kg diet) on weaned piglets (Duroc × Landrace × Yorkshire, 28 d of age; n = 8). After a 28-d feeding trial, supplementation at 500–2,000 mg/kg significantly improved average daily gain and feed efficiency and reduced diarrhoea frequency, with maximal benefits observed at 1,000 mg/kg ( P < 0.0001). Additionally, 500–1,000 mg/kg sodium isobutyrate supplementation increased the apparent digestibility of crude protein, organic matter, and crude fibre ( P < 0.05). Serum biochemical parameters were unaffected, although secretory immunoglobulin A (SIgA) levels significantly increased upon supplementation with 500–1,000 mg/kg ( P < 0.05). 16S rRNA gene sequencing indicated that sodium isobutyrate increased the abundance of beneficial colonic microbiota. The 1,000 mg/kg group presented the most pronounced effect, with a significant increase of the relative abundance of Prevotella and the greatest improvement in SCFA concentrations ( P < 0.05). Metabolomics revealed elevated levels of colonic indole-3-lactic acid and 3-hydroxybutyrate upon supplementation with 1,000 mg/kg ( P < 0.05). Transcriptomic analyses indicated activation of protein digestion and absorption pathways, and PI3K-Akt signalling, marked by TSG-6 upregulation and the suppression of ISG15 and DDIT4 expression ( P < 0.05). Supplementation with 1,000 mg/kg was associated with improved intestinal barrier-related markers, including reduced serum D-lactate, diamine oxidase, and lipopolysaccharide levels, increased tight junction protein expression; activation of G protein-coupled receptors; and inhibition of TLR4/MyD88/NF-κB signalling ( P < 0.05), suggesting enhanced barrier function. Conclusions: In conclusion, dietary supplementation with 1,000 mg/kg sodium isobutyrate was associated with improved intestinal morphology, reduced serum permeability, increased expression of tight junction proteins, and enhanced immune function in weaned piglets, suggesting enhanced colonic barrier function and providing dosage guidance and mechanistic insights for future applications. Graphical