**5. Diet as a modulator of the microbiota-immune system cross-talk**

An adequate and appropriate nutritional status and composition of the diet, in terms of foods, nutrients, and bioactive substances, are critical for the proper functioning of the immune system, which in turn is a fine sensor of the nutritional status of the individual [39]. When the immune system is activated to respond to nonself antigens, the demand for energy and nutrients increases and cells undergo the metabolic switch [40], as previously mentioned in the 2.2 paragraph. The dependence of the immune response on energy, and therefore the onset of immune deficits as a result of undernutrition, is known for a long time, but recently it has been observed that also the excessive consumption of food and excessive intake of calories alter the immune system. In fact, if on the one hand a serious caloric restriction impairs immune system functionality and increases the risk of infections (as observed in childhood malnutrition, still widely spread in developing countries), on the other hand, an unbalanced diet rich in high-calorie foods leads to negative consequences, inducing an inflammatory state and metabolic disorders. Many metabolic diseases are in fact characterized by a chronic low-grade systemic inflammation, called metaflammation (metabolic inflammation). Obesity and overnutrition are both associated with this inflammatory state leading to an increased risk of cardiovascular disease, heart attack, type 2 diabetes, and nonalcoholic steatohepatitis [41].
