# Unlocking Wellness: Probiotics as Key Drivers in Functional Food Innovation and Health Promotion
## 3 The Function of Probiotics
### Enhancement of Intestinal Barrier Function  
The intestinal barrier is composed of mucosal epithelial cells, tight junction proteins, the mucus layer, and intestinal flora [38]. The gastrointestinal barrier is a key defense mechanism for maintaining epithelial integrity and preventing pathogen infection and excessive inflammation [39]. On the one hand, by increasing the expression of tight junction proteins, the intercellular gaps are reduced to 0.3-0.8 nm, thereby reducing intestinal permeability [40]. On the other hand, it directly stimulates goblet cells to secrete mucin (MUC2), which promotes the thickening of the mucus layer [41] and the proliferation and repair of epithelial cells [42], thereby enhancing the integrity of the mechanical barrier. Experimental evidence indicates that probiotic supplementation can increase intestinal mucus thickness by 30-50% [43]. Some strains reduce intestinal barrier damage by neutralizing pathogen toxins and harmful metabolites [44]. The lipopolysaccharide-LPS fragment expressed by _Escherichia coli Nissle 1917_ (ECN) mimics the structure of the Shiga toxin receptor Gb3, causing the B subunit of Shiga toxin to be misrecognized and to specifically bind to ECN's LPS, thereby firmly fixing the toxin to the ECN surface. The toxin-ECN complex is then expelled from the body via intestinal peristalsis, thereby protecting the host from toxin-mediated damage [45].  
The surface molecules of probiotics significantly modulate intestinal barrier function through interactions with host intestinal epithelial cells. For example, surface-layer proteins of probiotics competitively inhibit pathogen adhesion and enhance intestinal epithelial integrity by regulating tight-junction proteins and cytoskeletal distribution [46]. Flagellin is recognized by toll-like receptor 5 (TLR5) on the intestinal epithelial cell membrane and activates the downstream PI3K/Akt signaling pathway through the adapter protein myeloid differentiation primary response 88 (MyD88). The TLR5-MyD88 complex recruits phosphoinositide 3-kinase (PI3K), which catalyzes the production of the second messenger phosphatidylinositol (3,4,5)-trisphosphate (PIP\({}_{3}\)). PIP\({}_{3}\) binds to and recruits protein kinase B (Akt) to the cell membrane, where it is phosphorylated and activated by 3-phosphoinositide-dependent protein kinase 1 and mTOR complex 2. Activated phosphorylated Akt phosphorylates and inhibits the transcription factor FOXOO1 while activating the transcription factors cAMP response element-binding protein and activator protein 1 (AP-1), thereby significantly promoting the transcription of antimicrobial peptides and exerting anti-inflammatory and antimicrobial effects [47]. In addition, flagellar proteins activate the pattern recognition receptor TLR4/MD2 complex by binding to glycoproteins on the surface of intestinal epithelial cells. This interaction triggers intracellular MyD88- and TRIF-dependent signaling pathways and induces the activation of transcription factors (nuclear factor kappa-B (NF-\(\kappa\)B), AP-1, and interferon regulatory factor 3), thereby promoting intestinal barrier function and mucosal immunity [48]. Podocarp polysaccharides interact with host receptors to regulate cytokine secretion and reduce intestinal inflammation [49]. These surface molecules bind specifically to host receptors, activate downstream signaling pathways, and promote intestinal health by enhancing the tight junctions of intestinal epithelial cells and promoting mucus secretion while inhibiting pathogen adhesion and invasion, ultimately maintaining the integrity of the intestinal barrier [50].