Abstract: Compositions and methods are provided herein for treating intestinal glycocalyx dysfunction. The composition can comprise a chito-oligosaccharide (COS), and optionally a human milk oligosaccharide (hMO) in an amount sufficient to maintain an intestinal glycocalyx and a pharmaceutically acceptable carrier. The composition can be formulated as an oral dosage form or a parenteral dosage form. The method can comprise identifying intestinal glycocalyx dysfunction in the subject. The method can further comprise administering to the subject a COS in an amount and at a frequency sufficient to prevent, stabilize and reverse damage in the intestinal glycocalyx.