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Starve a fever

Screen Shot 2015-04-14 at 4.01.28 AMA study by Pickard and colleagues in Nature showed that exposure to lipopolysaccharide, LPS, causes anorexia. This component of sickness behavior is well known, and LPS administration is a commonly used model for illness anorexia. The figure below shows a dramatic decrease in energy intake after receiving LPS:

Both solid bars (Fut2+) and open bar (Fut 2-) had markedly decreased food intake after LPS.

In a new and important finding these authors also showed that LPS makes the host secrete carbohydrates on the intestinal epithelium. This effect depended on production of fucosylated oligosaccharides, the gene for which is FUT2. FUT2 positive mice produce these carbohydrates rapidly after stress from LPS with the consequence of directly feeding gut commensal microbiota.

Thus, LPS is an agonist for N-fucosylation and has the effect of diverting a nutrient source to commensal bacteria. N-fucosylation benefits the host in this instance by feeding beneficial barrier bacteria.  Selection may have favored this mutualism because commensal bacteria help prevent invasion by gut pathogens.

In other words sickness makes you eat less, but you may continue to feed your gut microbes. Exposure to LPS induces “sugaring” of intestinal epithelial cells with fucosylated oligosaccharides, as seen in the fluorescence image below:

Screen Shot 2015-04-14 at 9.28.32 AM

So indeed our bodies do starve a fever (LPS is a well known pyrogen), but we feed our commensals. (Now by we I mean mammals.) This was a mouse study, and humans differ in at least one important respect. Some humans lack functional Fut2, preventing the ability to secrete fucosylated oligosaccharides. Fut2 negative humans are at higher risk of inflammatory bowel disease and neonatal sepsis. Not surprisingly Fut2 in humans shows evidence of ongoing natural selection.

The consequence of FUT2 in humans was covered in detail in a previous post on this blog. Read on.

Related: Faecal microbiota composition in adults is associated with the FUT2 gene determining the secretor status.

And: Innate Susceptibility to Norovirus Infections Influenced by FUT2 Genotype in a United States Pediatric Population.

Categories: Uncategorized

Joe Alcock

Emergency Physician, Educator, Researcher, interested in the microbiome, evolution, and medicine

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