Probiotic Bacteria Induce Maturation of Intestinal Claudin 3 Expression and Barrier Function

Abstract

An immature intestinal epithelial barrier may predispose infants and children to many intestinal inflammatory diseases, such as infectious enteritis, inflammatory bowel disease, and necrotizing enterocolitis. Understanding the factors that regulate gut barrier maturation may yield insight into strategies to prevent these intestinal diseases. The claudin family of tight junction proteins plays an important role in regulating epithelial paracellular permeability. Previous reports demonstrate that rodent intestinal barrier function matures during the first 3 weeks of life. We show that murine paracellular permeability markedly decreases during postnatal maturation, with the most significant change occurring between 2 and 3 weeks. Here we report for the first time that commensal bacterial colonization induces intestinal barrier function maturation by promoting claudin 3 expression. Neonatal mice raised on antibiotics or lacking the toll-like receptor adaptor protein MyD88 exhibit impaired barrier function and decreased claudin 3 expression. Furthermore, enteral administration of either live or heat-killed preparations of the probiotic Lactobacillus rhamnosus GG accelerates intestinal barrier maturation and induces claudin 3 expression. However, live Lactobacillus rhamnosus GG increases mortality. Taken together, these results support a vital role for intestinal flora in the maturation of intestinal barrier function. Probiotics may prevent intestinal inflammatory diseases by regulating intestinal tight junction protein expression and barrier function. The use of heat-killed probiotics may provide therapeutic benefit while minimizing adverse effects.

Effect of dietary isoleucine on the immunity, antioxidant status, tight junctions and microflora in the intestine of juvenile Jian carp (Cyprinus carpio var. Jian)

“…Claudin 3 is a tightening TJ protein that aids in sealing of the paracellular intestinal barrier, and impaired expression may lead to intestinal disease in mice [74]. In vertebrate, claudin-7 could also play a role in tightening of epithelial barriers [74]. Surprisingly, our results showed that Ile deficiency up-regulated gene expressions of occludin, claudin-3 and claudin-7 in the intestine of Jian carp.…”

“…In vitro, down-regulation of occludin gene blocked the formation of the paracellular seal in human epidermal keratinocytes [73]. Claudin 3 is a tightening TJ protein that aids in sealing of the paracellular intestinal barrier, and impaired expression may lead to intestinal disease in mice [74]. In vertebrate, claudin-7 could also play a role in tightening of epithelial barriers [74].…”

Modulatory Effects of Gut Microbiota on the Central Nervous System: How Gut Could Play a Role in Neuropsychiatric Health and Diseases

“…For example, in experimental models of colitis, several species of probiotics including Lactobacillus, Escherichia coli, and Bifidobacterium can reduce gut permeability by upregulating trans-membrane proteins that are important in preserving tight junctions between epithelial cells. [30][31][32][33] It has also been shown that treatment with these probiotics can enhance mucus production and consequently improve the physical barrier protecting the epithelial layer. 34,35 Products of bacterial fermentation can also play an important role in maintaining the intestinal barrier.…”

Probiotics and necrotizing enterocolitis

“…However, alteration of gut flora is only one potential mechanism by which probiotics might prevent NEC. Other mechanisms include effects on the gut immune system and via TLR-related signaling [76,77] and effects on mucosal integrity and intestinal permeability [78,79]. However, whether these are primary or secondary effects is extremely difficult to dissect, as the microbiome, immune system, mucosal integrity and gut barrier function are all mutually interdependent.…”