Sulfoglycolysis sustains Eubacterium rectale in low-fiber diets

The production of short-chain fatty acids by Firmicutes within the human gastrointestinal tract is recognized as critical for gut health and the progression of a range of disease states. Firmicutes lack many glycan-degrading pathways and instead derive a major proportion of their metabolic precursors from carbohydrates released by glycan-degrading generalists belonging to the Bacteroidota phylum and Bifidobacteriaceae family. Recently, it was shown that Eubacterium rectale, a widespread member of the Firmicutes belonging to the Clostridiales cluster XIVa, can grow on the unusual but ubiquitous plant-derived sugar sulfoquinovose (SQ) using a sulfoglycolytic sulfofructose transaldolase pathway. Here, we show that in addition to SQ, E. rectale can also grow on the SQ glycoside sulfoquinovosyl glycerol (SQGro). The 3D structure of the E. rectale sulfoquinovosidase shares strong structural conservation with SQases from gram-negative bacteria. Using sequence-similarity networks, we provide new biological context to a conserved domain of unknown function protein SftX belonging to DUF4867, which is conserved in the sulfoglycolytic sulfofructose transaldolase pathway and determine its 3D structure. Finally, with the aid of a synthetic mini-human microbiome reconstituted in germ-free mice, we show that an SQ dietary supplement can rescue E. rectale from population crashes that occur upon switching from a high-fibre to a low-fibre, high-fat diet. This suggests that SQ or SQGro has potential as a prebiotic for promoting the maintenance of this important SCFA-producing bacterium within the colonic microbiota.