Next-generation prebiotic promotes selective growth of bifidobacteria, suppressing Clostridioides difficile

Gut Microbes. 2021 Jan-Dec;13(1):1973835. doi: 10.1080/19490976.2021.1973835.

Abstract

Certain existing prebiotics meant to facilitate the growth of beneficial bacteria in the intestine also promote the growth of other prominent bacteria. Therefore, the growth-promoting effects of β-galactosides on intestinal bacteria were analyzed. Galactosyl-β1,4-l-rhamnose (Gal-β1,4-Rha) selectively promoted the growth of Bifidobacterium. Bifidobacterium longum subsp. longum 105-A (JCM 31944) has multiple solute-binding proteins belonging to ATP-binding cassette transporters for sugars. Each strain in the library of 11 B. longum subsp. longum mutants, in which each gene of the solute-binding protein was disrupted, was cultured in a medium containing Gal-β1,4-Rha as the sole carbon source, and only the BL105A_0502 gene-disruption mutant showed delayed and reduced growth compared to the wild-type strain. BL105A_0502 homolog is highly conserved in bifidobacteria. In a Gal-β1,4-Rha-containing medium, Bifidobacterium longum subsp. infantis JCM 1222T, which possesses BLIJ_2090, a homologous protein to BL105A_0502, suppressed the growth of enteric pathogen Clostridioides difficile, whereas the BLIJ_2090 gene-disrupted mutant did not. In vivo, administration of B. infantis and Gal-β1,4-Rha alleviated C. difficile infection-related weight loss in mice. We have successfully screened Gal-β1,4-Rha as a next-generation prebiotic candidate that specifically promotes the growth of beneficial bacteria without promoting the growth of prominent bacteria and pathogens.

Keywords: Clostridioides difficile; Prebiotic; bifidobacteria; microbiome; microbiota; probiotic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Animals
  • Bifidobacterium / genetics
  • Bifidobacterium / growth & development*
  • Bifidobacterium longum subspecies infantis / genetics
  • Bifidobacterium longum subspecies infantis / growth & development*
  • Clostridioides difficile / growth & development*
  • Disaccharides / pharmacology*
  • Gastrointestinal Microbiome / drug effects
  • Humans
  • Intestines / microbiology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Prebiotics / analysis*

Substances

  • ATP-Binding Cassette Transporters
  • Disaccharides
  • Prebiotics
  • galactosylrhamnose

Supplementary concepts

  • Bifidobacterium longum subsp. longum

Grants and funding

This work was supported by the Science and Technology Research Promotion Program for Agriculture, Forestry, Fisheries and Food Industry (25010A) and the Lotte Research Promotion Grant and by Grants-in-Aid from the Institute for Fermentation, Osaka (K-25-04, G2019-2-020);Grants-in-Aid from Institute for Fermentation, Osaka [K-25-04];Grants-in-Aid from Institute for Fermentation, Osaka [K-25-04];Grants-in-Aid from Institute for Fermentation, Osaka [G2019-2-020];