Isthmin1 (ISM1) is a constitutively secreted cytokine produced by barrier tissues and different immune cell types. Importantly, ISM1 is also expressed by cells with a hematopoietic stem cell phenotype in the lung and plays a role during hematopoiesis. Under inflammatory conditions, ISM1 levels are also altered. Given that the intestine is one of the tissues with the highest ISM1 gene expression, in this work, we characterized the immunophenotype of ISM1-producing cells in the small intestine of uninfected or Typhimurium-infected mice. We found a variety of ISM1+-expressing cells, including CD45+ cells, EpCAM+ cells, and, importantly, we also found different subsets of cells carrying hematopoietic stem cell markers (LSKs) expressing ISM1, and their frequency was perturbed during infection. Finally, we also found that isthmin1 is secreted into the intestinal lumen, and its concentration was increased during Typhimurium infection. Our findings suggest that increased luminal ISM1 secretion during mucosal infection may serve as a potential novel biomarker of pathogen-mediated inflammation.