Lipopolysaccharide and the gut microbiota: considering structural variation

Alex E. Mohr, Meli'sa Crawford, Paniz Jasbi, Samantha Fessler, Karen L. Sweazea

Research output: Contribution to journalReview articlepeer-review

40 Scopus citations


Systemic inflammation is associated with chronic disease and is purported to be a main pathogenic mechanism underlying metabolic conditions. Microbes harbored in the host gastrointestinal tract release signaling byproducts from their cell wall, such as lipopolysaccharides (LPS), which can act locally and, after crossing the gut barrier and entering circulation, also systemically. Defined as metabolic endotoxemia, elevated concentrations of LPS in circulation are associated with metabolic conditions and chronic disease. As such, measurement of LPS is highly prevalent in animal and human research investigating these states. Indeed, LPS can be a potent stimulant of host immunity, but this response depends on the microbial species’ origin, a parameter often overlooked in both preclinical and clinical investigations. Indeed, the lipid A portion of LPS is mutable and comprises the main virulence and endotoxic component, thus contributing to the structural and functional diversity among LPSs from microbial species. In this review, we discuss how such structural differences in LPS can induce differential immunological responses in the host.

Original languageEnglish (US)
Pages (from-to)849-875
Number of pages27
JournalFEBS Letters
Issue number7
StatePublished - Apr 2022


  • gut barrier
  • gut microbiome
  • immunity
  • inflammation
  • lipopolysaccharide binding protein
  • lipopolysaccharide variant
  • lipopolysaccharides
  • metabolic endotoxemia
  • obesity

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology


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