Human Gut Faecalibacterium prausnitzii Deploys a Highly Efficient Conserved System To Cross-Feed on β-Mannan-Derived Oligosaccharides

mBio. 2021 Jun 29;12(3):e0362820. doi: 10.1128/mBio.03628-20. Epub 2021 Jun 1.


β-Mannans are hemicelluloses that are abundant in modern diets as components in seed endosperms and common additives in processed food. Currently, the collective understanding of β-mannan saccharification in the human colon is limited to a few keystone species, which presumably liberate low-molecular-weight mannooligosaccharide fragments that become directly available to the surrounding microbial community. Here, we show that a dominant butyrate producer in the human gut, Faecalibacterium prausnitzii, is able to acquire and degrade various β-mannooligosaccharides (β-MOS), which are derived by the primary mannanolytic activity of neighboring gut microbiota. Detailed biochemical analyses of selected protein components from their two β-MOS utilization loci (F. prausnitzii β-MOS utilization loci [FpMULs]) supported a concerted model whereby the imported β-MOS are stepwise disassembled intracellularly by highly adapted enzymes. Coculturing experiments of F. prausnitzii with the primary degraders Bacteroides ovatus and Roseburia intestinalis on polymeric β-mannan resulted in syntrophic growth, thus confirming the high efficiency of the FpMULs' uptake system. Genomic comparison with human F. prausnitzii strains and analyses of 2,441 public human metagenomes revealed that FpMULs are highly conserved and distributed worldwide. Together, our results provide a significant advance in the knowledge of β-mannan metabolism and the degree to which its degradation is mediated by cross-feeding interactions between prominent beneficial microbes in the human gut. IMPORTANCE Commensal butyrate-producing bacteria belonging to the Firmicutes phylum are abundant in the human gut and are crucial for maintaining health. Currently, insight is lacking into how they target otherwise indigestible dietary fibers and into the trophic interactions they establish with other glycan degraders in the competitive gut environment. By combining cultivation, genomic, and detailed biochemical analyses, this work reveals the mechanism enabling F. prausnitzii, as a model Ruminococcaceae within Firmicutes, to cross-feed and access β-mannan-derived oligosaccharides released in the gut ecosystem by the action of primary degraders. A comprehensive survey of human gut metagenomes shows that FpMULs are ubiquitous in human populations globally, highlighting the importance of microbial metabolism of β-mannans/β-MOS as a common dietary component. Our findings provide a mechanistic understanding of the β-MOS utilization capability by F. prausnitzii that may be exploited to select dietary formulations specifically boosting this beneficial symbiont, and thus butyrate production, in the gut.

Keywords: butyrate producer; carbohydrate active enzymes; cross-feeding interactions; human gut microbiota; short-chain fatty acids; β-mannan; β-mannoligosaccharides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bacteroides / genetics
  • Bacteroides / metabolism
  • Clostridiales / genetics
  • Clostridiales / metabolism
  • Colon / microbiology
  • Diet
  • Faecalibacterium prausnitzii / genetics*
  • Faecalibacterium prausnitzii / growth & development
  • Faecalibacterium prausnitzii / metabolism*
  • Gastrointestinal Microbiome / genetics*
  • Gastrointestinal Microbiome / physiology
  • Humans
  • Mannans / classification
  • Mannans / metabolism*
  • Metagenomics
  • Oligosaccharides / metabolism*


  • Mannans
  • Oligosaccharides

Supplementary concepts

  • Bacteroides ovatus
  • Roseburia intestinalis