The balance of microbial species
in the intestine must be maintained
to prevent inflammation and disease. Healthy bacteria suppress infection
by pathogens and prevent disorders such as inflammatory bowel diseases
(IBDs). The role of mucus in the relation between pathogens and the
intestinal microbiota is poorly understood. Here, we hypothesized
that healthy bacteria inhibit infection by preventing pathogens from
penetrating the mucus layer and that microbial imbalance leads to
inflammation by promoting the penetration of the mucosal barrier.
We tested this hypothesis with an in vitro model that contains mucus,
an epithelial cell layer, and resident immune cells. We found that,
unlike probiotic VSL#3 bacteria, Salmonella penetrated the mucosal layers and induced the production of interleukin-8
(IL-8) and tumor necrosis factor (TNF)-α. At ratios greater
than 104:1, probiotic bacteria suppressed the growth and
penetration of Salmonella and reduced the production
of inflammatory cytokines. Counterintuitively, low densities of healthy
bacteria increased both pathogen penetration and cytokine production.
In all cases, mucus increased Salmonella penetration
and the production of cytokines. These results suggest that mucus
lessens the protective effect of probiotic bacteria by promoting barrier
penetration. In this model, a more imbalanced microbial population
caused infection and inflammation by selecting pathogens that are
more invasive and immunogenic. Combined, the results suggest that
the depletion of commensal bacteria or an insufficient dosage of probiotics
could worsen an infection and cause increased inflammation. A better
understanding of the interactions between pathogens, healthy microbes,
and the mucosal barrier will improve the treatment of infections and
inflammatory diseases.