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

BACKGROUND: 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. METHODS: Suckling rats were studied at 72 h 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. KEY RESULTS: 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. CONCLUSIONS & INFERENCES: 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.

Erratum: Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.

This corrects the article DOI: 10.1038/srep41802.

Reduction of Abeta amyloid pathology in APPPS1 transgenic mice in the absence of gut microbiota.

Alzheimer's disease is the most common form of dementia in the western world, however there is no cure available for this devastating neurodegenerative disorder. Despite clinical and experimental evidence implicating the intestinal microbiota in a number of brain disorders, its impact on Alzheimer's disease is not known. To this end we sequenced bacterial 16S rRNA from fecal samples of Aß precursor protein (APP) transgenic mouse model and found a remarkable shift in the gut microbiota as compared to non-transgenic wild-type mice. Subsequently we generated germ-free APP transgenic mice and found a drastic reduction of cerebral Aß amyloid pathology when compared to control mice with intestinal microbiota. Importantly, colonization of germ-free APP transgenic mice with microbiota from conventionally-raised APP transgenic mice increased cerebral Aß pathology, while colonization with microbiota from wild-type mice was less effective in increasing cerebral Aß levels. Our results indicate a microbial involvement in the development of Abeta amyloid pathology, and suggest that microbiota may contribute to the development of neurodegenerative diseases.