Antibiotic-induced perturbations in microbial diversity during post-natal development alters amyloid pathology in an aged APPSWE/PS1ΔE9 murine model of Alzheimer’s disease

• Published in: Scientific reports Vol. 7; no. 1; p. 10411
• Main Authors: Minter, Myles R., Hinterleitner, Reinhard, Meisel, Marlies, Zhang, Can, Leone, Vanessa, Zhang, Xiaoqiong, Oyler-Castrillo, Paul, Zhang, Xulun, Musch, Mark W., Shen, Xunuo, Jabri, Bana, Chang, Eugene B., Tanzi, Rudolph E., Sisodia, Sangram S.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.09.2017
• Subjects: 13/105; 13/51; 14/19; 38; 38/23; 631/250/371; 631/326/2522; 631/378/1689/1283; 631/378/371; 631/443/7; 64; 64/60; 82; 82/80; Humanities and Social Sciences; multidisciplinary; Science; Science (multidisciplinary)
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-017-11047-w

Recent evidence suggests the commensal microbiome regulates host immunity and influences brain function; findings that have ramifications for neurodegenerative diseases. In the context of Alzheimer’s disease (AD), we previously reported that perturbations in microbial diversity induced by life-long combinatorial antibiotic (ABX) selection pressure in the APP SWE /PS1 ΔE9 mouse model of amyloidosis is commensurate with reductions in amyloid-β (Aβ) plaque pathology and plaque-localised gliosis. Considering microbiota-host interactions, specifically during early post-natal development, are critical for immune- and neuro-development we now examine the impact of microbial community perturbations induced by acute ABX exposure exclusively during this period in APP SWE /PS1 ΔE9 mice. We show that early post-natal (P) ABX treatment (P14-P21) results in long-term alterations of gut microbial genera (predominantly Lachnospiraceae and S24-7 ) and reduction in brain Aβ deposition in aged APP SWE /PS1 ΔE9 mice. These mice exhibit elevated levels of blood- and brain-resident Foxp3 + T-regulatory cells and display an alteration in the inflammatory milieu of the serum and cerebrospinal fluid. Finally, we confirm that plaque-localised microglia and astrocytes are reduced in ABX-exposed mice. These findings suggest that ABX-induced microbial diversity perturbations during post-natal stages of development coincide with altered host immunity mechanisms and amyloidosis in a murine model of AD.