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We propose that IA\u00a0+\u00a0TC\u00a0+\u00a0IF or TC\u00a0+\u00a0IF\u00a0+\u00a0ice water gavage can be used to prepare comorbidity models in future. Maternal separation (MS) may also potentially become one of the effective models for studying comorbidities. In anxiety\/depression model, we show that both chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) are classical models for emotional disorders. We suggest CRS\/CUMS combines with IA\/IF\/TC can better to establish gastrointestinal\u2010emotional comorbidity model which through brain\u2013gut cross talk. Then the review also develops a comprehensive and standardized evaluation system for comorbidity models, with recording behavioral indicators related to gastrointestinal\/emotional disorders, while including multidimensional parameters such as the microbiota, neuroinflammation, metabolomics, brain\u2013gut peptide, and neurotransmitters.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This study is the first comprehensive comparison of FD and anxiety\u2013depression modeling protocols to propose effective protocols of comorbidity models and develop a comprehensive and standardized evaluation system for comorbidity models.<\/jats:p>\n                  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