Altered gut microbiota is responsible for pancreatic cancer progression. a. High-fat diet intake alters the gut microbiota composition. Altered gut microbiota secrete lipopolysaccharides (LPS), which enters circulation by damaging intestinal tight junction proteins. Circulatory LPS then binds to the toll like receptor on immune cells to recruit MyD88 or TRIF adaptor molecules. These molecules further activate MAPK and NF-κB pathways to activate several inflammatory cytokines, leading to cancer cell proliferation. b. Short-chain fatty acids (SCFAs) are released from resistant starch by the gut microbiota that enters the circulation. Afterward, SCFAs bind to G-protein-coupled receptors to activate the MAPK signaling pathway, triggering cancer cell proliferation.