Oral delivery of probiotics has shown promising effects in modulating the gut microbiota and treating ulcerative colitis (UC). However, the therapeutic efficacy is restricted by gastrointestinal assaults, poor mucosal adhesion, and single therapeutic modality. Here, we developed acid-resistant, gut-environment–responsive composite microparticles based on microfluidic electrospray for the oral codelivery of probiotic [Lactobacillus acidophilus (LA)] biofilm and postbiotics (indole-3-propionic acid). Montmorillonite was selected for supporting biofilm formation due to its cation-exchange capability and clearly defined biosafety. The montmorillonite-LA biofilm was effectively protected by the microparticles and markedly improved the intestinal retention. Upon oral administration, the composite microparticles notably alleviated colitis in mice, including reducing the inflammatory response, improving intestinal barrier function, and modulating the gut microbiota. Consequently, the composite microparticles show high potential for enhancing probiotic delivery efficacy and present a promising strategy for UC treatment.
It has long been known that probiotics can be used to maintain intestinal homeostasis and treat a number of gastrointestinal disorders, but the underlying mechanism has remained obscure. Recently, increasing evidence supports the notion that certain probiotic-derived components, such as bacteriocins, lipoteichoic acids, surface layer protein and secreted protein, have a similar protective role on intestinal barrier function as that of live probiotics. These bioactive components have been named ‘postbiotics’ in the most recent publications. We previously found that the Lactobacillus rhamnosus GG (LGG) culture supernatant is able to accelerate the maturation of neonatal intestinal defense and prevent neonatal rats from oral Escherichia coli K1 infection. However, the identity of the bioactive constituents has not yet been determined. In this study, using liquid chromatography-tandem mass spectrometry analysis, we identified a novel secreted protein (named HM0539 here) involved in the beneficial effect of LGG culture supernatant. HM0539 was recombinated, purified, and applied for exploring its potential bioactivity in vitro and in vivo. Our results showed that HM0539 exhibits a potent protective effect on the intestinal barrier, as reflected by enhancing intestinal mucin expression and preventing against lipopolysaccharide (LPS)- or tumor necrosis factor α (TNF-α)-induced intestinal barrier injury, including downregulation of intestinal mucin (MUC2), zonula occludens-1 (ZO-1) and disruption of the intestinal integrity. Using a neonatal rat model of E. coli K1 infection via the oral route, we verified that HM0539 is sufficient to promote development of neonatal intestinal defense and prevent against E. coli K1 pathogenesis. Moreover, we further extended the role of HM0539 and found it has potential to prevent dextran sulfate sodium (DSS)-induced colitis as well as LPS/D-galactosamine-induced bacterial translocation and liver injury. In conclusion, we identified a novel LGG postbiotic HM0539 which exerts a protective effect on intestinal barrier function. Our findings indicated that HM0539 has potential to become a useful agent for prevention and treatment of intestinal barrier dysfunction- related diseases.
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