(P20-047-23) Fecal Metabolites Potentially Mediate Diet-Induced Growth Patterns in Formula-Fed Infants Consuming a Meat- vs. Dairy-Based Complementary Diet

Objectives: To determine if fecal metabolites play a role in diet-induced growth differences observed in formula-fed infants consuming a meat- vs. dairy-based complementary diet.

Methods: Sixty-four formula-fed infants from Denver, Colorado completed a randomized controlled feeding trial consuming a meat- (n=32) or dairy-based (n=32) complementary diet from 5 to 12 months of age. Length-for-age Z scores (LAZ), increased in the meat group but decreased in the dairy group, while both groups had similar weight gains (Tang, AJCN 2018). Stool samples were collected at 5, 10, and 12 months of age and subjected to metabolomics analyses. For maximum coverage of metabolites, each sample was analyzed in both positive and negative modes of electron spray ionization with polar (HILIC) and nonpolar reverse phase (C18) UPLC columns using 1200 Agilent UPLC connected to Q-ToF-MS (6550, Agilent Inc, USA). A causal mediation analysis was conducted to estimate the proportion of the effect of dietary intervention on infants' growth that may be mediated by fecal metabolites.

Results: Over 4000 compounds were identified in the stool samples. N=571 had different abundance changes between diet groups from 5 to 12 months (P < 0.05, Test 1). Changes in abundances of n=1213 metabolites had a significant association with changes in growth Z scores (P < 0.05, Test 2). A total of n=110 metabolites that were significant in both Tests 1 and 2 were included in the mediation analyses as potential mediators. Of the 110 compounds, 40 compounds had P < 0.1 for the mediation analysis, while 7 compounds had P value < 0.05 suggesting possible mediation by fecal metabolites of diet-induced infant growth. Half of the putative mediating compounds identified were not annotated and need further investigation. Some of these compounds have been studied in other aspects of human physiology, including tenovin-6, dodecanedioic acid and acetylcarnitine.

Conclusions: Fecal metabolites may have mediated diet-induced growth differences in formula-fed infants consuming different types of protein-rich foods. Comprehensive literature review and targeted metabolomics are needed before definitive conclusions can be drawn.

Funding Sources: NIDDK 1K01DK111665, NIH/National Center for Advancing Translational Sciences (NCATS) Colorado CTSA UL1 TR001082, Abbott Nutrition, AHA, the Beef Checkoff, and the National Pork Board.