Impact of dietary induced precocious gut maturation on cecal microbiota and its relation to the blood-brain barrier during the postnatal period in rats.

Abstract

Precocious maturation of the gastrointestinal barrier (GIB) in newborn mammals can be induced by dietary provocation, but how this affects the gut microbiota and the gut-brain axis remains unknown. The objective of this study was to investigate effects of induced GIB maturation on gut microbiota composition and blood-brain barrier (BBB) permeability. Suckling rats were studied at 72h after gavage with phytohemagglutinin (PHA) or microbial protease (PT) to induce maturation of GIB. For comparison, untreated suckling and weaned rats were included (n=10). Human serum albumin (HSA) was administered orally and analyzed in blood to assess permeability of the GIB, while intraperitoneally injected bovine serum albumin (BSA) was measured in the brain tissue for BBB permeability. The cecal microbial composition, plasma lipopolysaccharide-binding protein (LBP) levels and short-chain fatty acids in serum and brain were analyzed. Cessation of HSA passage to blood after PHA or PT treatment was similar to that seen in weaned rats. Interestingly, concomitant increases in cecal Bacteroidetes and plasma LBP levels were observed after both PHA and PT treatments. The BBB passage of BSA was surprisingly elevated after weaning, coinciding with lower plasma LBP levels and specific microbial taxa and increased acetate uptake into the brain. This study provides evidence that the gut microbiota alteration following induced precocious GIB maturation may induce low-grade systemic inflammation and alter SCFAs utilization in the brain which may also play a potential role in GIB-BBB dysfunction disorders in neonates.