Gastrointestinal organoids represent a meaningful advance in structural and functional complexity over underlying in vitro cell culture models of the human gastrointestinal epithelium while maintaining much of the genetic and molecular acquiescence that makes in vitro experimentation so enchanting. Specific human models for studying the crosstalk between commensal bacteria and host interactions are crucial for better understanding gastrointestinal infections. Gastrointestinal organoids are ex vivo models that can be used to explore the various functions of healthy intestines in comparison with pathogen-infected tissues or to examine the effects of colonisation with one of several species of commensal bacteria. A robust human microbiome-gut-brain axis model with a potential to expand our understanding of this complex system and properly explore novel, microbiome-based pathogenesis needs to be developed to imitate the in vitro model to carry comprehensive studies of the mechanisms underlaying complex cross-talk within the microbiome-gut-brain axis and functional gastrointestinal disorders. A human epithelial organoid culture can be derived ex vivo from intestinal crypts isolated from biopsies and surgical specimens and has been shown to retain the specificity of the intestinal segment of origin. Therefore, the study of gastrointestinal organoids represents an effective strategy for dissecting the mechanisms underlying disease progression and the establishment of a healthy interplay. In this review, we provide an overview highlighting the importance of this model, its applications for the study of various gastrointestinal infections, and approaches for investigating how commensal bacteria contribute to eubiosis.