Abstract: The invention provides antibodies with superior therapeutic efficacy and related methods of engineering such antibodies to increase their stability and resistance to proteases, e.g., in the digestive tract. Protease cleavage motifs are identified and subsequently modified to reduce or eliminate cleavage at that site. Methods of employing these orally deliverable antibodies as therapeutic compositions, particularly against gastrointestinal pathogens are also provided herein. In one aspect, the invention provides combinations of monoclonal antibodies, e.g., “synthetic polyclonals,” that work synergistically to neutralize bacterial toxins, particularly enteric bacterial toxins such as Clostridium difficile toxin A.