Evaluating Prophylactic Effect of Bovine Colostrum on Intestinal Barrier Function in Zonulin Transgenic Mice: A Transcriptomic Study

Abstract

The intestinal barrier comprises a single layer of epithelial cells tightly joined to form a physical barrier. Disruption or compromise of the intestinal barrier can lead to the inadvertent activation of immune cells, potentially causing an increased risk of chronic inflammation in various tissues. Recent research has suggested that specific dietary components may influence the function of the intestinal barrier, potentially offering a means to prevent or mitigate inflammatory disorders. However, the precise mechanism underlying these effects remains unclear. Bovine colostrum (BC), the first milk from cows after calving, is a natural source of nutrients with immunomodulatory, anti-inflammatory, and gut-barrier fortifying properties. This novel study sought to investigate the transcriptome in BC-treated Zonulin transgenic mice (Ztm), characterized by dysbiotic microbiota, intestinal hyperpermeability, and mild hyperactivity, applying RNA sequencing. Seventy-five tissue samples from the duodenum, colon, and brain of Ztm and wild-type (WT) mice were dissected, processed, and RNA sequenced. The expression profiles were analyzed and integrated to identify differentially expressed genes (DEGs) and differentially expressed transcripts (DETs). These were then further examined using bioinformatics tools. RNA-seq analysis identified 1298 DEGs and 20,952 DETs in the paired (Ztm treatment vs. Ztm control) and reference (WT controls) groups. Of these, 733 DEGs and 10,476 DETs were upregulated, while 565 DEGs and 6097 DETs were downregulated. BC-treated Ztm female mice showed significant upregulation of cingulin (Cgn) and claudin 12 (Cldn12) duodenum and protein interactions, as well as molecular pathways and interactions pertaining to tight junctions, while BC-treated Ztm males displayed an upregulation of transcripts like occludin (Ocln) and Rho/Rac guanine nucleotide exchange factor 2 (Arhgf2) and cellular structures and interfaces, protein–protein interactions, and organization and response mechanisms. This comprehensive analysis reveals the influence of BC treatment on tight junctions (TJs) and Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kB) signaling pathway gene expressions. The present study is the first to analyze intestinal and brain samples from BC-treated Ztm mice applying high-throughput RNA sequencing. This study revealed molecular interaction in intestinal barrier function and identified hub genes and their functional pathways and biological processes in response to BC treatment in Ztm mice. Further research is needed to validate these findings and explore their implications for dietary interventions aimed at improving intestinal barrier integrity and function. The MGH Institutional Animal Care and Use Committee authorized the animal study (2013N000013).

Effect of bovine colostrum liposomes on the bioavailability of immunoglobulin G and their immunoregulatory function in immunosuppressed BALB/c mice

“…22 Besides, transcriptomic studies conducted by Asbjornsdottir et al suggested that the bioactive components in bovine colostrum, such as IgG and lactoferrin, might exert anti-inflammatory properties by regulating the NF-κB signaling pathway. 4 Our current research indicated that CTX caused an imbalance between the immunity-related cytokines and destroyed the intestine structure in BALB/c mice, and interestingly, after encapsulating by liposomes, bovine colostrum showed better characteristics for enhancing the IgG levels, rehabilitating the anti-inflammatory cytokines levels, and improving the intestine structure (Fig. 5–7).…”

“…1 The preliminary compositions that make up BC can be further divided into nutritional components (e.g., trans fatty acids, protein, and vitamins) and bioactive ingredients (e.g., immunoglobulins, growth factors, and hor-mones), among which the nutrient components are mainly responsible for providing energy to the body, while the bioactive ingredients meet the requirements of the body for growth and development and play crucial roles in fighting against diseases. 2,3 The high nutritional value and high bioactive functionality of bovine colostrum have attracted the attention of scientists around the world, and many researchers have revealed that the supplementation of bovine colostrum exhibits various health benefits, such as anti-inflammatory bowel disease (IBD), 2,4 anti-aging, 5 the management of immune-related syndromes, and the improvement of the athletic stamina. 6 Gaspar-Pintiliescu and colleagues co-cultured Candida lipolytica strains with kefir grains to obtain fermented bovine colostrum with high bioactive components, and they found that compared with water-soluble extracts of fermented colostrum, the bovine colostrum rich in bioactive ingredients exhibited better angiotensinconverting enzyme (ACE) inhibition and antioxidant activity.…”

Microbial interventions in yak colibacillosis: Lactobacillus-mediated regulation of intestinal barrier

“…Zonulin, considered a tight junction regulator, is associated with conditions such as diabetes and bipolar disorder (Craig Sturgeon and Fasano, 2016 ; Wood Heickman et al., 2020 ). We detected Zonulin expression in different treatment groups, noting that E. coli treatment resulted in Zonulin upregulation, generally considered a sign of intestinal tight junction destruction ( Asbjornsdottir et al., 2023 ; Zhao et al., 2023 ). This aligns with the down-regulation of tight junction-related proteins ZO-1 and Occludin observed previously.…”