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Canine S100A12 has potential as a biomarker of inﬂammation in dogs. Fecal S100A12 concentrations were increased in dogs with chronic gastroenteropathy (CE), and correlated with the severity of clinical and endoscopic disease. A negative outcome was associated with higher fecal S100A12 concentrations in CE dogs, but the response to diﬀerent forms of treatment and fecal S100A12 has not been reported, and this information will be important to further evaluate the utility of fecal S100A12 as a biomarker for gastrointestinal disease. Aim of this study was to evaluate the association between responses to various treatments (i.e., elimination diet, antimicrobial drugs, or corticosteroids/other immunosuppressants) and fecal S100A12 in dogs with CE. Fecal samples were collected from dogs diagnosed with CE, and fecal S100A12 was measured in all specimens using an established in-house ELISA. Based on the response to treatment, dogs were classiﬁed as having antibiotic-responsive diarrhea (ARD), food-responsive diarrhea (FRD), or steroid-responsive/therapy-resistant idiopathic inﬂammatory bowel disease (IBD). Statistical analysis was performed using non-parametric 2- or multiple-group comparisons, the likelihood ratio to evaluate the association between groups of dogs and response to treatment, and a receiver operating characteristic curve to calculate sensitivity and speciﬁcity at the optimum cut-oﬀ concentration. A total of 64 dogs with CE (median age: 6.3 years; 33 males/ 31 females) were included in the study, the ﬁnal diagnosis of which were ARD (n = 9), FRD (n = 30), or IBD (n = 25). Response to treatment was complete remission (n = 35), partial response (n = 25), or no response (n = 4). Fecal S100A12 concentrations ranged from 1 to 34,500 ng/g, and higher S100A12 levels were seen in dogs with IBD than in dogs with FRD ( P = 0.010) or ARD (P = 0.025). Dogs that did not respond to treatment had signiﬁcantly higher S100A12 levels than dogs with partial (P = 0.005) or complete (P = 0.003) remission, but response to treatment was associated with disease classiﬁcation (P = 0.020). Despite a small number of patients, fecal S100A12 levels of >2,700 ng/g at the time of diagnosis distinguished dogs that failed responding to treatment from those with at least partial remission with a sensitivity of 100% and speciﬁcity of 87%. We conclude that, in line with our previous ﬁnding that fecal S100A12 may be a useful biomarker of disease severity in dogs with IBD, fecal S100A12 may also have utility in predicting the lack of response to treatment in dogs with CE. The utility of serial fecal S100A12 concentrations to monitor treatment response in dogs with CE warrants further research.