Nutrient signaling

As we discussed in class, fatty acids have different effects on gut pathogens because of their structure. Polyunsaturated fatty acids with double bonds have a “kink” in their carbon chains. Saturated fatty acids have a straight conformation, as do trans fats. See the following figure adapted from Desbois & Smith (Appl Microbiol Biotechnol. 2010 85:1629–1642) which shows saturated fatty acids (stearic acid and lauric acid) look much like trans fat (elaidic acid), while polyunsaturated fat, aka PUFA are bent (eicosapentaenoic acid, a omega -3 fatty acid):

Long chain saturated fatty acids, because of their structure and high melting points, tend to stiffen the phospholipid bilayer when they are taken up into the cell membranes of bacteria (at least for some organisms). This makes membranes stiffer, and makes some bacteria more resistant to many stresses (such as high temperature during fever and exposure to gastric acid). Polyunsaturated fatty acids have a low melting point because their nonlinear conformation prevents close stacking, thus reducing the weak intermolecular bonds between hydrogen atoms. As the number of double bonds increases, so does the fluidity. This explains why PUFA like vegetable oils are liquid at room temperature while saturated fats like butter are solid. The same effect increases the fluidity of cell membranes and can decrease resistance to stress. PUFA can kill bacteria by themselves, with increasing antimicrobial effects with an increasing number of double bonds, as seen in the following figure adapted from Knapp and Melly ( J Infect Dis 154:1 84-93):

In this figure the number of carbon atoms is 20, and the number of double bonds follows the “:”. Saturated fatty acid fails to inhibit Staph aureus, while killing increases with each additional double bond.

It turns out that this pattern, increased antibacterial effects of unsaturated fat compared to saturated fat, holds for a variety of gut pathogens. This bioactivity of fatty acids may explain why the human immune system treats saturated fat and polyunsaturated fat differently.

 

Next week we are going to talk more about the Paleolithic diet and the evolution of lactase persistence.

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