Artificial cellulose derivatives are metabolized by select human gut Bacteroidota upon priming with common plant β-glucans.

Synthetic ethers of cellulose (β(1,4)-glucan) are widely used in the food and pharmaceutical industry as thickeners, gelling agents, emulsifiers, and stabilizers. Consequently, humans ingest significant amounts of artificial cellulose derivatives in diets containing processed foods and through oral drug formulations. In the present study, we examined the potential of mixed-linkage β-glucan (MLG) and xyloglucan (XyG) polysaccharide utilization loci of autochthonous human gut (gastrointestinal tract) Bacteroidota to enable metabolism of artificial cellulose derivatives, based on the commonality of their backbone linkages. Two representative Bacteroides and six representative Segatella (syn. Prevotella) strains all failed to grow on carboxymethyl cellulose (CMC, E466), methyl cellulose (MC, E461), hydroxypropyl methyl cellulose (HPMC, E464), and hydroxyethyl cellulose (HEC) as sole carbohydrate sources. However, remarkably, collateral metabolism of cellulose ethers was observed when bacteria were primed with low levels of cereal MLG or dicot XyG, in a species-dependent, strain-dependent, and polysaccharide-dependent manner. Using the type strain Segatella copri DSM18205 as an example, cellulose derivative utilization was rationalized by demonstrating that outer membrane-localized endo-glucanases were both transcriptionally upregulated and possessed side activities toward CMC, MC, HPMC, and/or HEC. On one hand, our results in vitro counter the conventional wisdom that soluble cellulose derivatives are non-metabolizable in the human gut. On the other hand, our study suggests that broader analysis of this underappreciated metabolic ability is warranted in a wider range of taxa, especially in consideration of potential physiological effects in the context of balanced diets comprising plant polysaccharides.IMPORTANCEOur data reveal a previously unknown potential among members of the human gut microbiota to metabolize artificial cellulose derivatives used in processed food and oral pharmaceuticals, which is driven by plant glycans ubiquitous in well-balanced diets containing natural dietary fiber. These results challenge the conventional wisdom that cellulose ethers are not broken down and metabolized in monogastric animals and motivate broader exploration of this phenomenon across the numerous autochthonous taxa.