Development of innovative tools for investigation of nutrient-gut interaction

Table 1 Available tools used for investigation of nutrient-gut interactions

Tools		Advantages	Disadvantages/challenges
Cellular models	EE cell lines	Established secretion profiles; genetically modifiable; readily accessible	Limited resemblance to native l-cells; lack of inter-organ interaction; limited success in clinical translation
Tissue-based approaches	Intestinal organoids	Preserved native architecture; region-specific functions; high plasticity for oriented differentiation	Undefined secretion profiles; lack of integrated nervous or immune systems; inconsistent culture outcomes
	Isolated intestinal tissues	Preserved native intestinal structure; access to luminal and basolateral surface; high physiological relevance	Short viable period; lack of inter-organ interaction; limited access to human tissue; low EE cell density
Intestinal intubation	In vivo infusion in gut	Region-specific delivery; direct insights into human (patho-)physiology	Technically demanding; restricted to specialised research centre
Novel techniques	3D culture	Enhanced anatomical complexity; compatibility with co-culture system	Limited cellular variety; static culture environment
	Intestine-on-a-chip	Dynamic culture environment; recapitulation of luminal events	Sophisticated validation of the system; partial resemblance to luminal physiology
	Ingestible sensors	A broad range of application; high potential for multi-purposed in vivo investigation	Difficulty in signal interpretation; lack of stability; High cost

EE: Enteroendocrine.