Trehalose-Induced Remodelling of the Human Microbiota Affects Clostridioides difficile Infection Outcome in an In Vitro Colonic Model: A Pilot Study

<jats:p>Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including <jats:italic>Clostridioides difficile</jats:italic>. Trehalose has been reported to enhance virulence of certain <jats:italic>C. difficile</jats:italic> ribotypes; however, such variants are widespread and not correlated with clinical outcomes for patients suffering from <jats:italic>C. difficile</jats:italic> infection (CDI). Here, we make preliminary observations on how trehalose supplementation affects the microbiota in an <jats:italic>in vitro</jats:italic> model and show that trehalose-induced changes can reduce the outgrowth of <jats:italic>C. difficile</jats:italic>, preventing simulated CDI. Three clinically reflective human gut models simulated the effects of sugar (trehalose or glucose) or saline ingestion on the microbiota. Models were instilled with sugar or saline and further exposed to <jats:italic>C. difficile</jats:italic> spores. The recovery of the microbiota following antibiotic treatment and CDI induction was monitored in each model. The human microbiota remodelled to utilise the bioavailable trehalose. Clindamycin induction caused simulated CDI in models supplemented with either glucose or saline; however, trehalose supplementation did not result in CDI, although limited spore germination did occur. The absence of CDI in trehalose model was associated with enhanced abundances of <jats:italic>Finegoldia</jats:italic>, <jats:italic>Faecalibacterium</jats:italic> and <jats:italic>Oscillospira</jats:italic>, and reduced abundances of <jats:italic>Klebsiella</jats:italic> and <jats:italic>Clostridium</jats:italic> spp., compared with the other models. Functional analysis of the microbiota in the trehalose model revealed differences in the metabolic pathways, such as amino acid metabolism, which could be attributed to prevention of CDI. Our data show that trehalose supplementation remodelled the microbiota, which prevented simulated CDI, potentially due to enhanced recovery of nutritionally competitive microbiota against <jats:italic>C. difficile</jats:italic>.</jats:p>