Colonic bacterial dysbiosis as a cause of infant proctocolitis

Food protein induced proctocolits (FPIP) of early infancy is clinically characterized by inflammation of the distal colon and rectum leading to bloody stools, a troublesome sign for clinicians as well as parents. Currently, this disease is pathophysiologically explained by a delayed (type 4) mucosal allergic reaction caused by food proteins, which in infants is almost always cows milk protein. Infants with FPIP are usually treated by changing the infants diet to an extensively hydrolyzed formula, which in most cases leads to the resolution of symptoms. The current pathophysiological explanatory model of an allergic mucosal inflammation as the cause of the disease has recently been challenged. Our preliminary findings have shown a statistically significant association of a positive stool culture for Klebsiella oxytoca with FPIP compared to healthy infants. Klebsiella oxytoca has been shown to cause hemorrhagic colonic inflammation due to toxin production in adults as well as in children. We interpret this finding as a surrogate marker for a pathological disturbance of the composition of the intestinal bacterial microbiota (termed dysbiosis). We hypothesize that intestinal microbiota dysbiosis rather than an allergic reaction is the cause of hemorrhagic colonic inflammation in infants with FPIP. Intestinal bacterial dysbiosis has been shown to be the cause of colonic hemorrhagic mucosal inflammation in a number of gastrointestinal diseases (e.g. Clostridium difficile colitis, antibiotic- associated hemorrhagic colitis, CED). Furthermore, it has been consistently demonstrated that a radical change in enteral nutrition has a profound impact on intestinal microbiota composition. The change to extensively hydrolyzed formula in infants with FPIP can therefore lead to resolution of symptoms by its influence on the enteral bacterial composition. We plan a prospective investigation of the intestinal microbiotia in infants with FPIP. In a longitudinal study design using 16s-rRNA analysis and metagenomics we will characterize the intestinal bacterial composition from stool samples of infants with FPIP and its temporal changes over the disease course compared to healthy controls. Furthermore, our study design will enable us to analyze the impact of the change in nutrition (extensively hydrolyzed formula) on intestinal microbiota in patients with FPIP. Klebsiella oxytoca strains isolated from FPIP patients and healthy controls will be analyzed in regard to pathogenicity (toxin production) and phylogenetic origin (MLST analysis). Our proposed study could lead to a major paradigm shift in the pathophysiological explanation of FPIP leading to a radical change in the clinical management of these patients.