A Multi-Strain Probiotic Formulation Improves Intestinal Barrier Function by the Modulation of Tight and Adherent Junction Proteins

Abstract

In healthy individuals, tight junction proteins (TJPs) maintain the integrity of the intestinal barrier. Dysbiosis and increased intestinal permeability are observed in several diseases, such as inflammatory bowel disease. Many studies highlight the role of probiotics in preventing intestinal barrier dysfunction. The present study aims to investigate the effects of a commercially available probiotic formulation of L. rhamnosus LR 32, B. lactis BL 04, and B. longum BB 536 (Serobioma, Bromatech s.r.l., Milan, Italy) on TJPs and the integrity of the intestinal epithelial barrier, and the ability of this formulation to prevent lipopolysaccharide-induced, inflammation-associated damage. An in vitro model of the intestinal barrier was developed using a Caco-2 cell monolayer. The mRNA expression levels of the TJ genes were analyzed using real-time PCR. Changes in the amounts of proteins were assessed with Western blotting. The effect of Serobioma on the intestinal epithelial barrier function was assessed using transepithelial electrical resistance (TEER) measurements. The probiotic formulation tested in this study modulates the expression of TJPs and prevents inflammatory damage. Our findings provide new insights into the mechanisms by which probiotics are able to prevent damage to the gut epithelial barrier.

The Crosstalk between Intestinal Epithelial Cells and Mast Cells Is Modulated by the Probiotic Supplementation in Co-Culture Models

“…The LPS induced the expected TEER reduction only in the absence of HMC-1.2 ( Figure 1 and Figure 2 ), indeed, it has been reported to impair tight junction strength [ 28 , 29 , 30 , 31 ] via TLR4-dependent activation of the membrane-associated adaptor protein focal adhesion kinase in Caco-2 monolayers [ 32 ]. Interestingly, we showed that both the exposure to the probiotic formulation for 24 h, and the presence of HMC-1.2, concurred to preserve the integrity of the epithelial layer, as demonstrated by the TEER values in the Caco-2/HT-29 co-cultures.…”

“…In particular, it modulates luminal metabolism, stabilizing the intestinal microbiota [ 47 ], and it is able to modulate the immune response in elderly patients if administered prior to the influenza vaccine [ 48 ]. Furthermore, this strain can stabilize tight junction proteins through exopolysaccharide and the production of butyrate, as active metabolites [ 28 , 49 ]. The influence of probiotics toward MCs was also demonstrated for the B longum KACC 91563, that induces MCs’ apoptosis [ 50 ], and for the probiotic formulation VSL#3, capable of reducing MC degranulation [ 51 ].…”

“…In particular, it was shown that the probiotic formulation was able to modulate indirectly the immune proinflammatory response of macrophages through the epithelial cell monolayer [ 24 ]. Furthermore, the ability of the tested probiotic formulation to prevent LPS-induced damage toward the intestinal epithelial layer was demonstrated when used in pre-treatment, prior to the LPS exposure [ 28 ].…”

“…The cells were challenged with the LPS proinflammatory stimulus and then treated with the Serobioma multi-strain probiotic formulation. The transepithelial electrical resistance (TEER) measurement was used to evaluate the barrier function of the cellular layers [ 28 ], while the inflammatory response was assessed by measuring cytokine production.…”

The Connection between Gut and Lung Microbiota, Mast Cells, Platelets and SARS-CoV-2 in the Elderly Patient

“…Since the gut microbiota communicates with the host through various biomolecules, pathways independent of the signalling of nutrients and epigenetic mechanisms, an alteration of these communication pathways related to age-related intestinal dysbiosis can heavily influence the health and life span of the host and trigger an innate immune response [ 45 ]. The circulation of bacterial compounds in the host is probably due to the breakdown of the intestinal epithelial barrier caused by the silent chronic inflammation state, and greater intestinal permeability has been suggested as a potential source of age-related inflammation [ 64 , 65 , 66 ].…”