Butyrate-producing colonic clostridia: picky glycan utilization specialists

Butyrate-producing human gut microbiota members are recognized for their strong associ-ation with a healthy immune-homeostasis and protection from inflammatory disorders and colorectal cancer. These effects are attributed to butyrate, the terminal electron sink of gly-can fermentation by prevalent and abundant colonic Firmicutes from the Lachnospiraceae and Oscillospiraceae families. Remarkably, our insight into the glycan utilization mecha-nisms and preferences of butyrogenic Firmicutes remains very limited as compared with other gut symbionts, especially from the Bacteroides, Bifidobacterium, and Lactobacillus genera. Here, we summarize recent findings on the strategies that colonic butyrate produc-ers have evolved to harvest energy from major dietary fibres, especially plant structural and storage glycans, such as resistant starch, xylans, and mannans. Besides dietary fibre, we also present the unexpected discovery of a conserved protein apparatus that confers the growth of butyrate producers on human milk oligosaccharides (HMOs), which are unique to mother's milk. The dual dietary fibre/HMO utilization machinery attests the adaptation of this group to both the infant and adult guts. These finding are discussed in relation to the early colonization of butyrogenic bacteria and the maturation of the microbiota during the transition from mother's milk to solid food. To date, the described butyrogenic Firmicutes are glycan utilization specialists that target only a few glycans in a highly competitive man-ner relying on co-regulated glycan utilization loci. We describe the common pillars of this machinery, highlighting butyrate producers as a source for discovery of biochemically and structurally novel carbohydrate active enzymes.

Automated summary

Butyrate-producing human gut microbiota members are associated with a healthy immune-homeostasis and protection from inflammatory disorders and colorectal cancer. This is due to the production of butyrate, which is produced by prevalent and abundant bacteria in the gut. However, our understanding of the glycan utilization mechanisms and preferences of these bacteria is limited. Recent findings have revealed the strategies used by these bacteria to harvest energy from dietary fibers and human milk oligosaccharides (HMOs). The discovery of a conserved protein apparatus that enables the growth of butyrate producers on HMOs highlights their adaptation to both infant and adult guts.