Abstract
The microbiota that colonises the intestinal mucus may particularly affect human health given its proximity to the epithelium. For instance, the presence of the adherent-invasive Escherichia coli (AIEC) in this mucosal microbiota has been correlated with Crohn’s disease. Using short-term screening assays and a novel long-term dynamic gut model, which comprises a simulated mucosal environment (M-SHIME), we investigated how (potential) pro- and prebiotics may repress colonisation of AIEC from mucus. Despite that during the short-term screening assays, some of the investigated Lactobacillus strains adhered strongly to mucins, none of them competed with AIEC for mucin-adhesion. In contrast, AIEC survival and growth during co-culture batch incubations was decreased by Lactobacillus rhamnosus GG and L. reuteri 1063, which correlated with (undissociated) lactic acid and reuterin levels. Regarding the prebiotics, long-chain arabinoxylans (LC-AX) lowered the initial mucin-adhesion of AIEC, while both inulin (IN) and galacto-oligosaccharides (GOS) limited AIEC survival and growth during batch incubations. L. reuteri 1063, LC-AX and IN were thus retained for a long-term study with the M-SHIME. All treatments repressed AIEC from mucus without affecting AIEC numbers in the luminal content. As a possible explanation, L. reuteri 1063 treatment increased lactobacilli levels in mucus, while LC-AX and IN additionally increased mucosal bifidobacteria levels, thus leading to antimicrobial effects against AIEC in mucus. Overall, this study shows that pro- and prebiotics can beneficially modulate the in vitro mucosal microbiota, thus limiting occurrence of opportunistic pathogens among those mucosal microbes which may directly interact with the host given their proximity to the epithelium.
Highlights
Along the intestinal tract, the host epithelium is covered by a protective mucus layer that contains specific microbes[1] and several factors contribute to a distinct microbiota in the luminal content versus the mucus layer.[2]
We provide an in vitro proof-of-principle that pre- and probiotic strategies can beneficially modulate the mucosal microbiota and decrease the mucosal colonisation of an opportunistic pathogen (i.e., Escherichia coli adherent-invasive Escherichia coli (AIEC))
Because the mucosal microbes may directly interact with the host, lowering the abundance of opportunistic pathogens in the mucosal compartment may be more relevant than lowering their abundance in the intestinal content
Summary
The host epithelium is covered by a protective mucus layer that contains specific microbes[1] and several factors contribute to a distinct microbiota in the luminal content versus the mucus layer.[2]. The unique mucosal microbiota composition is further determined by bacterial factors such as mucus adhesion[4] and mucin degradation.[5] The resulting mucosal microbiota as such possesses a colonisation resistance against opportunistic pathogens. This includes local excretion of antimicrobial compounds,[6] stimulation of the host immune system,[7] production of metabolic compounds that lower the pH8 and competition with pathogens for nutrients[9] and adhesion sites.[10]
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