Letter | Published:

Microbiota-liberated host sugars facilitate post-antibiotic expansion of enteric pathogens

Nature volume 502, pages 9699 (03 October 2013) | Download Citation



The human intestine, colonized by a dense community of resident microbes, is a frequent target of bacterial pathogens. Undisturbed, this intestinal microbiota provides protection from bacterial infections. Conversely, disruption of the microbiota with oral antibiotics often precedes the emergence of several enteric pathogens1,2,3,4. How pathogens capitalize upon the failure of microbiota-afforded protection is largely unknown. Here we show that two antibiotic-associated pathogens, Salmonella enterica serovar Typhimurium (S. typhimurium) and Clostridium difficile, use a common strategy of catabolizing microbiota-liberated mucosal carbohydrates during their expansion within the gut. S. typhimurium accesses fucose and sialic acid within the lumen of the gut in a microbiota-dependent manner, and genetic ablation of the respective catabolic pathways reduces its competitiveness in vivo. Similarly, C. difficile expansion is aided by microbiota-induced elevation of sialic acid levels in vivo. Colonization of gnotobiotic mice with a sialidase-deficient mutant of Bacteroides thetaiotaomicron, a model gut symbiont, reduces free sialic acid levels resulting in C. difficile downregulating its sialic acid catabolic pathway and exhibiting impaired expansion. These effects are reversed by exogenous dietary administration of free sialic acid. Furthermore, antibiotic treatment of conventional mice induces a spike in free sialic acid and mutants of both Salmonella and C. difficile that are unable to catabolize sialic acid exhibit impaired expansion. These data show that antibiotic-induced disruption of the resident microbiota and subsequent alteration in mucosal carbohydrate availability are exploited by these two distantly related enteric pathogens in a similar manner. This insight suggests new therapeutic approaches for preventing diseases caused by antibiotic-associated pathogens.

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European Nucleotide Archive

Data deposits

Microbiota enumeration (16S rRNA) datasets have been deposited in the EMBL European Nucleotide Archive (ENA) under accession number ERP003629 and can also be found in the QIIME Database under the study ID 1958 (http://www.microbio.me/qiime/). Gene Chip datasets are available in the GEO database under accession number GSE49076.


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We thank E. Sonnenburg for comments on the manuscript; M. St. Onge for technical assistance; and A. Shen, N. Minton and R. Knight for valuable help and reagents. This research was supported by R01-DK085025 (to J.L.S.), NSF graduate fellowships (to K.M.N. and J.A.F) and a Stanford Graduate Fellowship (to K.M.N.). J.L.S. holds an Investigators in the Pathogenesis of Infectious Disease Award from the Burroughs Wellcome Fund.

Author information

Author notes

    • Katharine M. Ng
    •  & Jessica A. Ferreyra

    These authors contributed equally to this work.

    • Purna C. Kashyap

    Present address: Department of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA.


  1. Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California 94305, USA

    • Katharine M. Ng
    • , Jessica A. Ferreyra
    • , Steven K. Higginbottom
    • , Jonathan B. Lynch
    • , Purna C. Kashyap
    • , Smita Gopinath
    • , Denise M. Monack
    •  & Justin L. Sonnenburg
  2. Glycobiology Research and Training Center, University of California, San Diego, California 92093, USA

    • Natasha Naidu
    •  & Biswa Choudhury
  3. Department of Population Health and Reproduction, University of California, Davis, California 95616, USA

    • Bart C. Weimer


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K.M.N., J.A.F., D.M.M. and J.L.S. designed experiments. K.M.N., J.A.F., S.K.H., J.B.L., P.C.K., N.N., B.C. and J.L.S. performed experiments. K.M.N., J.A.F., P.C.K., S.G., N.N., D.M.M. and J.L.S. analysed data. D.M.M. and B.C.W. contributed reagents. K.M.N., J.A.F. and J.L.S. wrote the paper.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Justin L. Sonnenburg.

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