| First Author | Lee HJ | Year | 2019 |
| Journal | Sci Rep | Volume | 9 |
| Issue | 1 | Pages | 11814 |
| PubMed ID | 31413350 | Mgi Jnum | J:284803 |
| Mgi Id | MGI:6387649 | Doi | 10.1038/s41598-019-48342-7 |
| Citation | Lee HJ, et al. (2019) Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice. Sci Rep 9(1):11814 |
| abstractText | To understand the role of commensal gut bacteria on the progression of cognitive decline in Alzheimer's disease via the microbiota-gut-brain axis, we isolated anti-inflammatory Bifidobacterium longum (NK46) from human gut microbiota, which potently inhibited gut microbiota endotoxin production and suppressed NF-kappaB activation in lipopolysaccharide (LPS)-stimulated BV-2 cells, and examined whether NK46 could simultaneously alleviate gut dysbiosis and cognitive decline in male 5xFAD-transgenic (5XFAD-Tg, 6 months-old) and aged (18 months-old) mice. Oral administration of NK46 (1 x 10(9) CFU/mouse/day for 1 and 2 months in aged and Tg mice, respectively) shifted gut microbiota composition, particularly Proteobacteria, reduced fecal and blood LPS levels, suppressed NF-kappaB activation and TNF-alpha expression, and increased tight junction protein expression in the colon of 5XFAD-Tg and aged mice. NK46 treatment also alleviated cognitive decline in 5XFAD-Tg and aged mice. Furthermore, NK46 treatment suppressed amyloid-beta, beta/gamma-secretases, and caspase-3 expression and amyloid-beta accumulation in the hippocampus of 5XFAD-Tg mice. NK46 treatment also reduced Iba1(+), LPS(+)/CD11b(+), and caspase-3(+)/NeuN(+) cell populations and suppressed NF-kappaB activation in the hippocampus of 5XFAD-Tg and aged mice, while BDNF expression was increased. These findings suggest that the suppression of gut dysbiosis and LPS production by NK46 can mitigate cognitive decline through the regulation of microbiota LPS-mediated NF-kappaB activation. |
