A high-fructose diet aggravated restraint stress-induced changes in the composition of the intestinal microbiome, in which the abundance of A. muciniphila was significantly increased. The high-fructose diet exacerbated restraint stress-induced the changes in the composition of the microbial metabolites, with taurine abundance being downregulated and histamine abundance upregulated.

Akkermansia muciniphila (A. muciniphila) is a mucin-degrading bacterium that resides in the mucus layer, but its potential in intestinal inflammatory diseases has sparked controversy. It is well known that both the consumption of fructose-containing beverages and psychological stress increase the risk of intestinal disease. Our results revealed that a high-fructose diet aggravated the damage to the jejunal mucosal barrier caused by restraint stress, reduced tight junction protein expression and the intestinal digestion and absorption capacity, disrupted the ability of Paneth cells to secrete antimicrobial peptides, and promoted the expression of inflammatory cytokines. A. muciniphila colonization enhanced the defense function of the mucosal barrier by enhancing the function of the NLRP6, promoting autophagy, maintaining the normal secretion of antimicrobial peptides in Paneth cells, promoting the expression of tight junction proteins, negatively regulating the NF-kB signaling pathway and inhibiting the expression of inflammatory cytokines. Our work indicates that A. muciniphila ameliorates the disruption of the intestinal mucosal barrier under high fructose and restraint stress. These results provided a rationale for the development of probiotic colonization for the prevention or treatment of intestinal diseases.

Stress may aggravate the development of inflammatory bowel disease and irritable bowel syndrome, in which the number of enterochromaffin (EC) cells and 5-hydroxytryptamine (5-HT) levels are abnormal, but the underlying mechanism remains largely unresolved. In this study, we discovered that restraint stress triggered the expression of Tph1, which led to 5-HT production. The 5-HT signaling then increased intestinal permeability, downregulated the expression of tight junction proteins, reduced the number of goblet cells and their ability to secrete mucin, promoted the expression of inflammatory cytokines, and ultimately damaged the intestinal mucosal barrier. Mechanistically, the 5-HT receptor HTR7 was highly expressed in the intestine. It interacted with 5-HT to initiate the Wnt/β-catenin signaling pathway, inducing an increase in intestinal EC cells and further promoting 5-HT secretion. Additionally, the activation of the Wnt/β-catenin signaling pathway could initiate the NF-κB signaling pathway and induce the expression of inflammatory cytokines. Blocking the 5-HT signal in mice inhibited the activation of the Wnt/β-catenin signal, thereby alleviating intestinal inflammation. Our findings revealed a novel role for 5-HT in intestinal inflammatory diseases and represent a potential new therapeutic target.

Xue X, et al. J Vet Sci. 2025 May;26:e38. https://doi.org/10.4142/jvs.24331

Background Chicken spleen transfer factor (TF) is a low-molecular-weight lymphocyte extract composed of polypeptide and nucleotide. This factor is obtained by repeated freeze-thaw dialysis of the specific-pathogen-free chicken spleen and can transfer cell-mediated immunity from immunocompetent donors to recipients. However, its role in regulating intestinal digestion and absorption and mucosal immunity in laying hens has remained largely unknown. Results To explore the effect of TF on intestinal mucosa barrier function, 100 one-day-old White Leghorns laying hens were randomly divided into five groups and administered with different doses of TF (0.00 [control], 0.05 mL, 0.10 mL, 0.25 mL, and 1.00 mL). The chickens received orally TF from days 5 to 12, and they were then raised a week without it. Tissue sampling was performed on the 12th and 19th days. The results showed that the high dose of TF (1.00 mL) improved the intestinal mucosa morphology and strengthened the digestive and absorption function. Furthermore, the histology analysis revealed an increase in the number of intraepithelial lymphocytes and goblet cells. Similarly, the results from ELISA demonstrated an increase in the content of IL-10 in the intestinal tract, while the content of TNF-α showed a decrease in this regard. The RT-PCR assay also demonstrated the upregulation of the relative mRNA expressions of Muc2, TLR-2, and TLR-4 genes in the small intestine and rectum. The intestinal antioxidant function was significantly enhanced. After stopping the TF administration for a week, its effect on the intestinal mucosa barrier was still detectable; however, it was followed by a weakened effect. Conclusions In conclusion, high-dose (TF-1.00mL) of TF can improve the intestinal mucosa morphology and structure, enhance digestion and absorption functions, enhance the intestinal mucosal barrier immune function and antioxidant function, and up-regulate Muc2, TLR-2 and TLR-4 gene relative expression.

Background: Feline panleukopenia, caused by the highly lethal feline parvovirus (FPV), lacks effective prevention and treatment strategies. This study aimed to elucidate the key metabolic regulatory mechanisms during FPV infection.Methods: CRFK cells were infected with the FPV013 strain. Viral identification was performed via cytopathic effect (CPE) observation, transmission electron microscopy (TEM), PCR, and VP2 protein detection using Western blot and immunofluorescence. Untargeted metabolomics analyzed metabolic changes at 12 h, 24 h, and 48 h post-infection (hpi). Key pathways were validated through enzyme activity inhibition (Meclizine targeting PCYT2) and gene silencing (siRNA targeting PLPP1 and LPIN3).Results: Metabolomics revealed the most significant differences at 48 hpi, identifying six significantly altered glycerophospholipid metabolites. Inhibiting PCYT2 enzyme activity significantly reduced viral load (p < 0.01). Silencing either phospholipid phosphatase 1 (PLPP1) or LPIN3 significantly inhibited FPV replication, with IF staining showing reduced VP2 expression (p < 0.01). In contrast, blocking fatty acid synthesis (TOFA/C75 treatment) had no significant effect.Conclusion: FPV infection promotes replication by reprogramming host cell glycerophospholipid metabolism. The PCYT2-mediated PE/PC synthesis pathway and the PLPP1 or LPIN3 regulated diacylglycerol (DG) generation pathway play central roles. This finding highlights the pivotal role of glycerophospholipid metabolism during FPV infection, offering insights into antiviral strategies targeting this pathway.