The Association between Intestinal Fatty Acid Biding Protein and Enteric Pathogens

Introduction: Enteric pathogens account for an unacceptable number of pediatric deaths in Sub-Saharan Africa (SSA) every year. Intestinal fatty acid binding protein (I-FABP) is a small intracellular protein released into the bloodstream when intestinal epithelial cells are damaged and can be used to measure gut damage and recovery. This study aimed to compare I-FABP concentration in children with at least one of the following four pathogens of interest: Shigella, Campylobacter, EAEC, and Giardia to children without a pathogen of interest identified at enrollment as well as determine whether children randomized to a 5-day course of azithromycin have lower I-FABP levels 3 months after discharge than those randomized to placebo. Methods: In this retrospective cohort study, we utilized linear regression models to assess the connection between I-FABP and each pathogen of interest in 1361 enrollment samples from children under 5 years old recently discharged from the hospital collected from the Toto Bora Trial. A subset of 971 children had additional plasma specimens available for I-FABP assessment at month 3. Linear regression was used for the secondary analysis with a likelihood ratio test of nested models. Results: A total of 60.8% of the children had at least one pathogen of interest at enrollment. Of those children with a pathogen of interest, 11.9% had a Shigella infection, 33.2% had Giardia, 9.0% had Campylobacter, and 74.2% had enteroaggregative Escherichia coli. Mean I-FABP concentration at enrollment for children without a pathogen of interest was similar when compared to the mean of all pathogens of interest combined (no pathogen of interest mean= 1653.1 pg/mL, all pathogens of interest mean =1663.4). Increased I-FABP was, however, found to be significantly associated with younger age, being underweight, and being stunted (all p-values<0.01), while decreased I-FABP was observed in children who received an antibiotic during their hospital stay (p=0.038). No significant difference was found in the mean I-FABP levels of children with or without a pathogen of interest both individually by pathogen and collectively (each comparison, p>0.05). Unexpectedly, I-FABP levels significantly increased from enrollment to 3 months post discharge in all groups (+337.61 pg/mL, p<0.05). The I-FABP level difference between enrollment and month 3 and was found to be 74.17 pg/mL less in the AZM randomization group compared to placebo [95% CI = (-253.23, 104.88 pg/mL)] but was not statistically significant (p=0.416). Conclusions: Higher I-FABP levels were found in malnourished children and lower I-FABP levels were found in children who had received antibiotics at their hospital stay prior to study initiation. We did not find an association between any of the pathogens we examined and I-FABP level, except for an inverse association with Shigella cycle thresholds. In contrast to our hypothesis that I-FABP levels would decrease during the post-discharge period, we found that I-FABP increased in all groups after hospitalization discharge in our cohort and was not associated with randomization arm. Further research is needed to understand why intestinal inflammation may increase following discharge, and whether this increase has clinical significance.