Regulation of gut epithelial barrier by microbiome metabolites

World Immune Regulation Meeting XVII 2023, Zürich, İsviçre, 5 - 08 Temmuz 2023, cilt.17, sa.48, ss.47-48

The human body is colonized by a diverse microbial flora that plays

an essential role in human health and disease. As the outermost layer,

the gut microbiota acts as the first line of defense against pathogenic

microorganisms in the gastrointestinal system. It is known that a

healthy gut microbiota limits pathogen colonization through competition

for space and nutrients, and by producing antimicrobial peptides

and metabolites that promote epithelial homeostasis. However, the

increased exposure to food additives such as emulsifiers and food

colorants, in processed food poses a significant threat to the gastrointestinal

epithelial barrier. In this context, the microbiota and their

metabolites could be the key to rescuing the damaged gastrointestinal

barrier. With this perspective, we identified four different microbiome

metabolites that elicit a rescue activity against the epithelial barrier

damage of sunflower-derived lecithin using a Caco-2 microfluidic-titer

plate. Transepithelial electrical resistance (TER) measurement, paracellular

permeability assay, immunofluorescence staining of tight

junction proteins, and targeted proteomics using proximity extension

assay were performed. Our results revealed that compound X and

V alone increased the TER value during the development phase of

the gut barrier. Furthermore, when the gut barrier developed in the

presence of compound X, it exhibited a preventive effect against the

damage caused by sunflower-derived lecithin, as demonstrated by

TER and paracellular permeability assays. The expression of tight

junction proteins claudin 1 and 4 were also increased with compound

X treatment, compared to the control and sunflower-derived lecithin treated

conditions. Moreover, compound X displayed a wide range

of anti-inflammatory effects, as detected by targeted proteomics and

RNA sequencing. Immunofluorescence staining of occludin and ZO-1

on a gut-on-a-chip model indicated irregular and heterogeneous protein localization after exposure to lecithin. Interestingly, the gut barrier

developed in the presence of compound X demonstrated resistance

to the damage caused by sunflower-derived lecithin, as demonstrated

by immunofluorescence staining. In conclusion, our current data

highlights compound X, a microbiome metabolite, as a promising

agent for rescuing and treating the gut epithelial barrier disruption.

Its ability to enhance barrier function, modulate tight junction protein

expression, and anti-inflammatory properties showcases its potential

preventive and therapeutic value.