Mechanistic Insights Into the Cross-Feeding of and on Host and Dietary Carbohydrates.

Dietary and host glycans shape the composition of the human gut microbiota with keystone carbohydrate-degrading species playing a critical role in maintaining the structure and function of gut microbial communities. Here, we focused on two major human gut symbionts, the mucin-degrader ATCC 29149, and L2-63, a keystone species for the degradation of resistant starch (RS) in human colon. Using anaerobic individual and co-cultures of and grown on mucin or starch as sole carbon source, we showed that starch degradation by supported the growth of whereas did not benefit from mucin degradation by . Further we analyzed the growth (quantitative PCR), metabolite production (H NMR analysis), and bacterial transcriptional response (RNA-Seq) of cultured with RS or soluble starch (SS) in the presence or absence of . In co-culture fermentations on starch, H NMR analysis showed that benefits from transient glucose and malto-oligosaccharides released by upon starch degradation, producing acetate, formate, and lactate as main fermentation end-products. Differential expression analysis (DESeq 2) on starch (SS and RS) showed that the presence of induced changes in transcriptional response of genes encoding several maltose transporters and enzymes involved in its metabolism such as maltose phosphorylase, in line with the ability of to utilize starch degradation products. In the RS co-culture, showed a significant increase in the induction of tryptophan (Trp) biosynthesis genes and a decrease of vitamin B12 (VitB12)-dependent methionine biosynthesis as compared to the mono-culture, suggesting that Trp and VitB12 availability become limited in the presence of . Together this study showed a direct competition between and on RS, suggesting that , the population inhabiting the mucus niche may be modulated by the supply of non-digestible carbohydrates reaching the colon such as RS.