It is unclear if guar gum can alleviate colorectal cancer (CRC). We evaluated the effect of guar gum (unmodified) on the mortality, colon status, serous tumor necrosis factor-alpha (TNF-α) concentration, and gut microbial and colonic epithelial cell gene expression profiles in CRC mice and performed omics analyses to compare these with those of Ganoderma lucidum polysaccharide (GLP), whose main component is β-glucan (>90%). We found that guar gum had a CRC alleviating effect. However, it showed a 20% higher mortality rate, shorter colon length, worse colon status, larger number and size of tumors, higher concentration of serous TNF-α and upregulation of epithelial cell genes (Il10, Cytl1, Igkv7-33, Ighv1-14, Igfbp6 and Foxd3) compared to that of GLP. The higher relative abundance of Akkermansia, the alteration of microbial metabolic pathways, especially those involving chaperones and folding catalysts, fatty acid biosynthesis, glycerophospholipid metabolism, glycolysis/gluconeogenesis, lipid biosynthesis and pyruvate metabolism, and the upregulation of specific genes (Mcpt2, Mcpt9, Des and Sostdc1) were also determined in animals fed a guar gum diet. The results suggested that the alleviating effect of guar gum (an inexpensive polysaccharide) on CRC was inferior to that of GLP (a more expensive polysaccharide). This could potentially be attributed to the increased presence of Akkermansia, the alteration of 10 microbial metabolic pathways and the upregulation of 4 epithelial cell genes.