Diet composition, ingredient and nutrients, are important to consider for maintaining intestinal functions. Studies on both positive (using feed additives) and negative effects (using high inclusion of plant ingredients) of fish feeds are numerous, however, between studies results are often highly variable, both in type of response and in significance. The central hypothesis of this study was that adverse environmental conditions may aggravate negative effects of plant ingredients on the intestinal functions to the extent that mild effects become severe and perceptible. To do so, dietary factors and environmental conditions were evaluated and the interaction between diet composition and environmental conditions were studied in Nile tilapia. In Chapter 2, six common raw materials including hydrolysed feather meal (HFM), soybean meal (SBM), rice bran (RB), rapeseed meal (RM), sunflower meal (SFM) and dried distiller grains with solubles (DDGS) were chosen to determine the effect of nutrient digestibility, nitrogen/energy balance and changes in intestinal morphology. The study demonstrated that feed ingredients do have an impact on the alteration in intestinal parameters, but also on the nutrient digestibility and the nitrogen/energy balance. Although being well digested, soybean meal caused the most obvious alteration in the intestinal morphology. These alterations were not related to the nutrient digestibility nor to nitrogen/energy balance parameters. Soybean meal, causing the most alterations in the intestinal morphology, was further used in all subsequent chapters of this thesis. Chapter 3 and 4 described the interaction between diet composition and environmental conditions on the intestinal functions. This was studied with two different environmental conditions, dissolved oxygen (Chapter 3) and salinity (Chapter 4). These two chapters evaluated whether suboptimal environmental conditions (low dissolved oxygen or elevated salinity in water) may interact with a soybean meal based diet in nutrient digestion and intestinal morphology of tilapia. The study demonstrated that environmental stressors can aggravate/reveal the negative intestinal morphology changes induced by a soybean meal based diet. However, these effects of adverse environmental conditions on the intestinal functions were not homogenously dispersed over the whole intestinal length. The effect of salinity on the intestinal morphology occurred predominantly in the distal intestine, whereas the effect of low oxygen concentration was more visible at the proximal intestine. Alterations in the intestinal morphology, as found in this study, have wider effects on the performance of the affected fish. In Chapter 3, the protein digestibility decreased under hypoxic conditions at week 8, which parallels with the time related alteration in intestinal morphology. Chapter 4 showed that when fish were raised at 15 ‰ salinity, nutrient digestibility increased; however, this positive effect decreased when the intestinal morphology changed. The study also found that the combined effect of a soybean meal based diet and hypoxia was stronger compared to the combination with elevated salinity. Therefore, the combination with hypoxia was further used in the next study of this thesis. In Chapter 5, the combination of hypoxic condition and a soybean meal based diet was chosen to test the hypothesis that only under stressful conditions, the effects of feed additives can be noticed. The impact of two dietary organic acids, formic acid and butyric acid, on nutrient digestibility and intestinal morphology was determined under optimal (normoxia) and suboptimal conditions (hypoxia). The results showed that although organic acids did not significantly improve growth performance and nutrient digestibility under normoxic condition, they did so under hypoxic conditions. Fish fed organic acid supplemented diets all showed improvements in the morphology of intestine under normoxic conditions, and these effects were more enhanced under hypoxic conditions. This indicates that environmental conditions can alter the effect of organic acid on nutrient digestibility and intestinal morphology in tilapia. Finally, Chapter 6 provided a synthesis of the main findings, and a reflection on the methodologies used in Chapters 2-5 as well as a discussion on the relevance of this study to aquaculture. It is concluded that although being well digested, soybean meal caused the most obvious alteration in intestinal morphology. The adverse environmental conditions aggravated negative effects of soybean meal based diets on the intestinal functions to the extent that mild effects become severe and visible. The negative effect on intestinal morphology of soybean meal in the diet is enhanced at low oxygen level and at elevated salinity. The effect of salinity on the intestinal morphology occurs predominantly in the distal intestine, whereas the effect of low oxygen concentration is more visible at the proximal intestine. The thesis indicated that the impact of organic acids on intestinal functions is dependent on environmental conditions, being more pronounced under challenging conditions (e.g. hypoxia). Therefore, studies on both positive (using feed additives) and negative effects (using high inclusion of plant ingredients) of dietary factors should be done under suboptimal conditions.