Suppression of gut dysbiosis by Bifidobacterium longum alleviates cognitive decline in 5XFAD transgenic and aged mice
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Abstract 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-κB 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 × 109 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-κB activation and TNF-α 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-β, β/γ-secretases, and caspase-3 expression and amyloid-β accumulation in the hippocampus of 5XFAD-Tg mice. NK46 treatment also reduced Iba1+, LPS+/CD11b+, and caspase-3+/NeuN+ cell populations and suppressed NF-κB 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-κB activation.
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Oral Bifidobacterium longum NK46 in 5xFAD mice suppressed Aβ accumulation in the hippocampus.
“The human isolate Bifidobacterium longum (NK46) was orally administered in 5xFAD mice and induced anti-inflammatory effects (decrease in lipopolysaccharide (LPS) levels, NF-κB activation, and TNF-α expression), changes in the intestinal microbiota composition of the recipients (increase in Bacteroides and reduction in Firmicutes and Proteobacteria phyla), and suppression of Aβ accumulation in the”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [170]
Oral Bifidobacterium longum NK46 in 5xFAD mice changed intestinal microbiota composition, increasing Bacteroides and reducing Firmicutes and Proteobacteria phyla.
“The human isolate Bifidobacterium longum (NK46) was orally administered in 5xFAD mice and induced anti-inflammatory effects (decrease in lipopolysaccharide (LPS) levels, NF-κB activation, and TNF-α expression), changes in the intestinal microbiota composition of the recipients (increase in Bacteroides and reduction in Firmicutes and Proteobacteria phyla), and suppression of Aβ accumulation in the”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [170]
Oral Bifidobacterium longum NK46 in 5xFAD mice induced anti-inflammatory effects, including decreased LPS levels, NF-κB activation, and TNF-α expression.
“The human isolate Bifidobacterium longum (NK46) was orally administered in 5xFAD mice and induced anti-inflammatory effects (decrease in lipopolysaccharide (LPS) levels, NF-κB activation, and TNF-α expression), changes in the intestinal microbiota composition of the recipients (increase in Bacteroides and reduction in Firmicutes and Proteobacteria phyla), and suppression of Aβ accumulation in the”
From The gut-brain axis: how microbiota and host inflammasome influence brain physiology and pathology (2020) · cites this paper as [170]
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- Authors
- Lee, H.-J., Lee, K.-E., Kim, J.-K., & Kim, D.-H.
- Affiliations
- Kyung Hee University (KR)
- Corresponding author
- Kim, Dong-Hyun
- Venue
- Scientific Reports
- Published
- 2019-08-14
- Volume
- 9
- Issue
- 1
- Pages
- 11814-11814
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC6694197
- OpenAlex
- W2967026120
- Cited by
- 164
- References
- 50
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 29 · 2023: 23 · 2022: 28 · 2021: 27 · 2020: 14 · 2019: 1
- FWCI
- 5.87
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Scientific Reports (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Research Foundation of Korea (2017R1A5A2014768)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Gut microbiota and health
- Health Sciences › Medicine › Physiology › Alzheimer's disease research and treatments
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- Bifidobacterium longum, gut dysbiosis, cognitive decline, Alzheimer's disease, 5xFAD mice, aged mice, microbiota-gut-brain axis, lipopolysaccharide, NF-κB activation, endotoxin production, tight junction proteins, amyloid-beta, caspase-3, brain-derived neurotrophic factor, neuroinflammation, hippocampus
- MeSH terms
- Gastrointestinal Microbiome, Bifidobacterium longum, Aging, Animals, Feces, Humans, Lipopolysaccharides, Mice, Transgenic, Probiotics, Mice, Cognitive Dysfunction, Dysbiosis
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