Our next stop on the hypotheses of modern disease train is the Antinutrient/Irritant Hypothesis. It goes like this...
Many plants produce organic defense compounds to make it less likely that they will be eaten. Some are much less obvious about it than, say, poison ivy. Grains and legumes in particular contain classes of compounds that are antinutrients (prevent the absorption of nutrients) or irritants. The most well known examples are the compound in peanuts that causes a severe allergic response in some people and the gluten in wheat which is a major problem for those with celiac or other sensitivities. But all grains and legumes have similar compounds. These obviously cause many problems for those with sensitivities (milk too for adults who are sensitive), but they could easily also be causing problems for the population at large, or low level sensitivities could be much more common than people think. It would be smart to avoid consuming all plants that contain defense compounds if they are not part of the diet that humans have evolved to eat. People with gut issues will usually see an improvement with a paleo diet and this is why. This hypothesis is best stated by Robb Wolf in the book Paleo Solution. The Wheat Hypothesis is really a special case of the Antinutrient/Irritant Hypothesis.
What do I think? Could be true. As someone without any particular sensitivities to food (but who got obese and had high cholesterol and some minor examples of modern disease - carries, gum disease, acid reflux, elevated blood pressure, etc) it isn't super compelling for those things (well, maybe acid reflux). You can craft really compelling theories that explain autoimmune disorders and inflammatory disease, but the biochemistry isn't as compelling for obesity and metabolic syndrome. Although what kills you in metabolic disease is most assuredly inflammatory effects.
Once again, though, notice that if it is true, a paleo diet protects you.