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

Anthony M Buckley,Mark H Wilcox,Ines B Moura,Georgina Davis,Takanobu Higashiyama,Suparna Mitra,Karen Bentley,Dapeng Wang,Norie Arai,Emma Clark,Hannah C Harris,William Spittal,Yoshihiro Nishida

doi:10.3389/fcimb.2021.670935

Anthony M Buckley, Mark H Wilcox + Show 11 more

Open Access

https://doi.org/10.3389/fcimb.2021.670935

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Abstract

Within the human intestinal tract, dietary, microbial- and host-derived compounds are used as signals by many pathogenic organisms, including Clostridioides difficile. Trehalose has been reported to enhance virulence of certain C. difficile ribotypes; however, such variants are widespread and not correlated with clinical outcomes for patients suffering from C. difficile infection (CDI). Here, we make preliminary observations on how trehalose supplementation affects the microbiota in an in vitro model and show that trehalose-induced changes can reduce the outgrowth of C. difficile, 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 C. difficile 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 Finegoldia, Faecalibacterium and Oscillospira, and reduced abundances of Klebsiella and Clostridium 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 C. difficile.

Highlights

Trehalose is a disaccharide sugar consisting of two a-glucose monomers linked via 1,1-glycosidic bond and is present in a wide variety of organisms, such as bacteria, yeast, insects, plants, and animals
Bifidobacteriaceae did decrease in all models one week later, which was confirmed by direct enumeration
The consumption of trehalose has been proposed to contribute to the emergence and virulence of C. difficile infection (CDI) outbreaks, in those RTs harbouring genetic trehalose metabolism variants (Collins et al, 2018a; Collins et al, 2018b)

Summary

Introduction

Trehalose is a disaccharide sugar consisting of two a-glucose monomers linked via 1,1-glycosidic bond and is present in a wide variety of organisms, such as bacteria, yeast, insects, plants, and animals. The structure of trehalose makes it highly resistant to acid hydrolysis, it is used as a high energy storage molecule for insect flight, and as a dehydration or cryo-protectant in some microorganisms, plants and animals (Elbein et al, 2003) This sugar is naturally found in foods, such as mushrooms and honey, but following the discovery of a cost-effective method of large-scale production (Maruta et al, 1995) and regulatory approval as a food additive, trehalose is added to a range of processed food products (cereals, pasta, sweets and ice cream), cosmetics and some medicines (Food Standards Australia New Zealand (FSANZ), 2003; Pinto-bonilla et al, 2015). Saund et al found no statistically significant association between the presence of trehalose utilisation variants in infecting C. difficile strains and the development of severe infection outcome (Saund et al, 2020)

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