To investigate the molecular mechanism underlying the development of diarrhea-predominant irritable bowel syndrome (IBS-D) with spleen and kidney yang deficiency (SKYD) using a proteomics approach.

Male Sprague–Dawley rats (n = 22) were divided into IBS-D (n = 12) and normal control (n = 10) groups. SKYD was then modeled in IBS-D rats by a combination of acetic acid enema, bondage, rectal dilation, tail stimulation, and Senna gavage. Colon tissue samples were subsequently collected and examined by Q Exactive mass spectrometry to identify differentially expressed proteins between the two groups.

The occurrence of SKYD/IBS-D was associated with ribosomal protein S23 (Rps23), protein phosphatase 2 catalytic subunit alpha (Pp2a), and growth factor receptor-bound protein 2 (Grb2), which are involved in the ribosome, neurotrophin signaling, and Janus kinase–signal transducer and activator of transcription (JAK–STAT) signaling pathways.

These data suggest that SKYD/IBS-D pathophysiology likely involves inflammation, cell growth, apoptosis, stress granule formation, immune activation, loss of epithelial cell integrity, and visceral hypersensitivity.