The premise of these mini-posts comes from Thomas Dobzhansky’s famous observation “nothing in biology makes sense except in the light of evolution.” In each of these posts, we will identify a medical Dobzhansky puzzle – something that makes no sense except in the light of evolution.

For each puzzler, we can identify the evolutionary piece that is missing. In particular, we will examine whether a genetic conflict may account for some of the manifestations of a disease. Secondly, we will ask whether the microbiome is involved, and look at whether co-evolutionary pressures have shaped disease traits. Ready for this? Alright. Let’s go!

We are going to start with malabsorption syndromes. In some stages of life we find that we cannot absorb the nutrients that we absolutely need. Why is that. Adults sometimes cannot take up iron, or carbohydrates or fat. When infants get sick, they often cannot take up lactose, contributing to diarrhea in both groups. Why do sick children become lactose transiently lactose intolerant? Why does milk contain lactose in the first place. What is up with celiac disease.

During gastroenteritis, some children develop diarrhea, in part because they stop absorbing lactose which gets delivered to the colon, serving as substrate for colonic bacteria and causing osmotic diarrhea.

Why does lactase stop working?

A possible answer – microbes are almost always involved. Infection at the epithelial – microbial interface interferes with lactase expression, and that segment of the intestine stops taking up lactase. This might happen because instead of being taken up by damaged or infected tissues, the resources can be diverted to the infecting organism, making things worse for the host. thereby delivering increased substrate. It is possible that is it in the hosts best internet to stop absorbing lactose, so that it is not cleaved into glucose which can fuel the growth of pathogens. This is perhaps a clue to lactose intolerance itself. Another idea is that during the weaning process it might be better to keep fuel away from microbes that can increase the oxygen content of the gut, antagonizing anaerobes.

My suspicion is that this is a microbe driven phenomenon. Lactose is safe to digest when the gut is dominated by HMO fermenting bacteria. When they are absent, Proteobacteria blooms are likely and lactose digestion stops. It is relevant that compared to glucose, growth of E. coli lower on lactose.

Lactose itself has a antibacterial effect. compared to maltodextrin, colostrum with lactose protected against NEC. Lactose causes Klebsiella growth inhibition likely because of pH, here. In this study, lactose slightly inhibits cell growth in the exponential growth phase, and is converted to lactic acid which inhibits bacterial growth. Lactose is also substrate for human milk oligosaccharides, and the benefit of HMO are so beneficial to infant growth and immunity. On other hand, the lac operon permits E. coli to have selective advantage in the infant gut.

Babies are protected, in part by packaging food in a way that antagonizes bacterial growth.

We should learn from babies and milk. Perhaps adult food is healthiest when it is packaged in a way that antagonizes bacterial growth.

So maybe babies when sick stop absorbing and metabolizing lactose because it too preferentially feeds microbes that compete and inhibit the growth of pathogens.

Lactose also prevents ammonia metabolic production, which might be useful to a baby vulnerable to NEC.

Finally, diarrhea itself is likely beneficial in the clearance of microbial pathogens. Although diarrhea is dangerous to babies. Not being able to have diarrhea is likely even worse. Evidence for this comes from studies of antimotility agents, contraindicated in infants.

So the answer for why lactose is no longer taken up by sick infants has to do with the protective effects of lactose in combination with all the other anti microbial and immune active constituents of milk. It may be dangerous to metabolize lactose to glucose that can be scavenged by pathogens.