The interplay of gut microbiota with the kidney system, characteristic to reduced kidney function and increased concentrations of urea in gut; in turn increases bacterial urease activity and generation of uremic toxins. Knowledge on these underlying bidirectional molecular mechanisms is nevertheless still limited. In this exploratory study, fecal proteomics analysis was performed, to investigate this largely unexplored biological material as a source of relevant information reflecting the gut-kidney axis at protein level. Specifically, fecal suspension samples from patients with chronic kidney disease (CKD); CKD1 (n = 12) and CKD4 (n = 17) were analysed by high resolution LC-MS/MS. Protein identification was performed using both the human and bacterial UniProt RefSeq reviewed databases, identifying 701 and 1011 unique proteins, respectively. Differential expression analysis (CKD4/CKD1) revealed significance for human proteins previously associated with reduced saccharolytic fermentation, inflammation and CKD, including pancreatic alpha-amylase and galectin-3-binding protein. Significant changes in bacterial proteins such as glyceraldehyde-3-phosphate dehydrogenase, suggest differential butyrate synthesis in CKD4/CKD1. Quantitatively measured decrease of pancreatic alpha-amylase and butyrate in CKD4/CKD1, supported these hypotheses. In conclusion, this analysis highlighted the presence of inflammation and suggested reduced saccharolytic fermentation affecting butyrate synthesis pathways in later disease stages. Validation by a multi-omics analysis is planned.