B. infantis EVC001 Metabolites Improve Enterocyte Proliferation In Vitro

Abstract

Bacterial metabolites, including short chain fatty acids (SCFA) are essential for host cells to maintain homeostasis. Previous findings showed exclusively breastfed infants colonized with B. infantis EVC001 have significantly increased fecal organic acid concentrations, specifically lactate and acetate as compared to infants not colonized with B. infantis, we investigated the effect of fecal water (FW) from two distinct populations on enterocyte proliferation and morphology in vitro. FW were derived from fecal samples from infants colonized with B. infantis EVC001 (EVC001) and infants not colonized with B. infantis (controls) were added to adult and premature enterocyte cell lines to assess growth, proliferation and cytotoxicity. Microscopic images were taken to observe morphological differences. Intestinal epithelial cells (IECs; Caco-2 and HIEC-6 cells) exposed to EVC001 FW showed significantly increased proliferation shown by ATP expression compared to medium alone and control FW (P < 0.0001). Conversely, significantly decreased lactate dehydrogenase, an indication of decreased membrane integrity, was detected in enterocytes exposed to EVC001 FW compared to controls FW (P < 0.01). Specific bacterial metabolites, lactate and acetate at median physiological concentrations found in EVC001 infant FW significantly increased Caco-2 intestinal integrity measured by transepithelial electrical resistance compared to medium alone (P < 0.01, P < 0.05, respectively), while control levels did not significantly increase proliferation. Furthermore, control FW altered the morphology of enterocytes compared to cells exposed to EVC001 FW or medium alone. EVC001 FW and specific bacterial metabolites, lactate and acetate significantly increased enterocyte proliferation compared to control FW and medium alone, while control FW negatively affected cell growth, membrane integrity and cell morphology; suggesting metabolites produced by B. infantis EVC001 promote enterocyte growth and improve intestinal integrity in both adult and premature infants. Evolve Biosystems.