Recent results showed that solid food disintegration in the stomach may be affected by food texture which was demonstrated to change during digestion. Cheese is complex as, depending on the variety, its composition and texture can be modulated. Cheddar, light Cheddar, Mozzarella and light Mozzarella cheese particles were digested in vitro. Cheese disintegration and nutrients release were studied throughout the oral, gastric and duodenal digestion steps in presence or absence of enzymes. Cheese disintegration was significantly affected by the enzymatic treatment (with or without enzymes). The addition of enzymes allowed to reach 72% of cheese disintegration at the end of the duodenal digestion while it has attained 30% when no enzymes were added. Cheddar cheese disintegration was the highest among cheeses. This phenomenon was related to its initial higher fat content which resulted in a higher fat release during digestion. The disintegration at the end of each digestion step was also correlated to cheese composition (proteolysis and fat) and to textural parameters (hardness, resilience, adhesiveness and chewiness). Light Cheddar and Mozzarella exhibited similar disintegration and nutrients release at the end of the digestion due to a relatively small fat reduction (6%) which had limited effect on cheese texture. This study provides quantitative evidence regarding the impact of cheese textural changes during digestion on cheese disintegration and macronutrients release which may further affect nutrients anabolic response and some physiological functions.