Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model

Abstract

Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P < 0.01). Compared with the LPS group, bifidobacterium significantly decreased the production of IL-6 and TNF-α (P < 0.01) and suppressed zonulin release (P < 0.05). In addition, bifidobacterium pretreatment up-regulated occludin, claudin-3 and ZO-1 expression (P < 0.01) and also preserved these proteins localization at TJ compared with the LPS group. In the in vivo study, bifidobacterium decreased the incidence of NEC from 88 to 47% (P < 0.05) and reduced the severity in the NEC model. Increased levels of IL-6 and TNF-α in the ileum of NEC rats were normalized in bifidobacterium treated rats (P < 0.05). Moreover, administration of bifidobacterium attenuated the increase in intestinal permeability (P < 0.01), decreased the levels of serum zonulin (P < 0.05), normalized the expression and localization of TJ proteins in the ileum compared with animals with NEC. We concluded that bifidobacterium may protect against intestinal barrier dysfunction both in vitro and in NEC. This protective effect is associated with inhibition of proinflammatory cytokine secretion, suppression of zonulin protein release and improvement of intestinal TJ integrity.

Bifidobacterium breveUCC2003 induces a distinct global transcriptomic programme in neonatal murine intestinal epithelial cells

“…Although the mucus layer may impact direct Bifidobacterium -IEC interactions, previous studies have indicated that B. breve UCC2003 surface molecules, such as EPS and the Tad pilus may modulate IEC function via signaling through TLRs [17, 49]. Moreover, bifidobacterial metabolites, such as short-chain fatty acids may also act to modulate the IEC transcriptome, with previous studies indicating enhanced expression of TJs and cadherins via acetate [9, 14, 50, 51].…”

Protective Effects of Lignite Extract Supplement on Intestinal Barrier Function in Glyphosate-Mediated Tight Junction Injury

“…Some natural substances that have shown such improvement include quercetin, butyrate, L-glutamine, and the probiotic Bifidobacterium, and the lignite extract compound studied herein [19,[22][23][24][25][26][27][28][29][30][31][32]. Larazotide, a synthetic pharmaceutical and zonulininhibitor, has also shown to improve tight junction formation [33].…”

“…Transepithelial electrical resistance (TEER) is widely accepted as an indicator of tight junction permeability [17][18][19][20]. TEER was measured in both IEC-6 and Caco-2 cells seeded in 24-well transwell plates (1-micron pore size, Becton Dickinson).…”

Exploring the role of the microbiota member Bifidobacterium in modulating immune-linked diseases

“…emphasise the importance of the species and even the strain of Bifidobacterium that is used. In a necrotising enterocolitis (NEC, which is also linked to epithelial barrier disruption) mouse model, B. breve was shown to up-regulate TJ proteins Claudin 4 and Occludin [51], and a non-specified species of Bifidobacterium increased ZO-1 in a rat NEC model [8]. Studies have also shown that the effects of bifidobacteria are only exerted, or are increased, when live bifidobacteria are used.…”

“…Bifidobacteria have been used for many years as supplements to promote host wellbeing, as their presence, including the high levels observed in infants and stable levels in adults, is associated with a 'healthy' state. These bacteria are particularly effective at protecting against infectious diseases [4][5][6][7] and modulating immune responses [7,8]. This review discusses Bifidobacterium across the life course, and focuses on species and specific strains that have been studied in the context of immune modulation and treatment of disease.…”