Diabetic and overweight cats have altered gut microbial diversity and composition.

Despite similarities in the pathophysiology of type 2 diabetes mellitus in humans and cats, the specific role of the gut microbiota in feline diabetes remains unclear. We determined the ileal microbiota composition of lean, overweight, and diabetic cats, and assessed the association of the ileal gut microbiota with key markers of insulin signaling and glucose regulation in the pancreas and muscle, and liver fat content. Ileal contents were collected from a client-owned population of total 32 (lean, n = 13; overweight, n = 8; diabetic=11) cats, and DNA extracted for 16S rRNA analyses. Results revealed significant differences in beta diversity between lean and diabetic cats, indicating distinct microbial community compositions. At the phylum level, relative abundance of Bacteroidota decreased in diabetics compared to lean and overweight cats. At the genus level, Alloprevotella was elevated in lean compared to overweight and diabetic cats. Further, Turicibacter was increased in treated diabetics compared to other groups. Partial least squares regression unveiled distinct microbial and tissue markers associated with diabetic status. Lean and overweight cats were associated with higher relative abundances of the genera Sutterella and Oscillibacter, and elevated muscle insulin receptor substrate-1, and pancreas insulin and insulin receptor mRNA levels. Conversely, diabetic cats were associated with higher relative abundances of the genera Peptostreptococcus and Escherichia-Shigella, and a higher liver fat percent. Together, these findings indicate that diabetic and overweight cats have distinct compositional differences in ileal microbiota, and that alterations in enteric microbial diversity and composition are associated with markers of insulin signaling in feline diabetes.