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Geroscience. 2019 Dec 8. doi: 10.1007/s11357-019-00137-4. [Epub ahead of print]

Lipoteichoic acid from the cell wall of a heat killed Lactobacillus paracasei D3-5 ameliorates aging-related leaky gut, inflammation and improves physical and cognitive functions: from C. elegans to mice.

Author information

1
Department of Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
2
Department of Endocrinology and Metabolism, Wake Forest School of Medicine, Winston-Salem, NC, USA.
3
Mouse Metabolic Phenotyping Core, Wake Forest School of Medicine, Winston-Salem, NC, USA.
4
Department of Pathology-Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
5
Biomedical Sciences, University of Tasmania, Hobart, Australia.
6
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
7
Department of Gerontology and Geriatric Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA.
8
Department of Cardiology, Wake Forest School of Medicine, Winston-Salem, NC, USA.
9
Department of Internal Medicine-Molecular Medicine, Wake Forest School of Medicine, Winston-Salem, NC, USA. hyadav@wakehealth.edu.
10
Department of Microbiology and Immunology, Wake Forest School of Medicine, Winston-Salem, NC, USA. hyadav@wakehealth.edu.

Abstract

Increased inflammation associated with leaky gut is a major risk factor for morbidity and mortality in older adults; however, successful preventive and therapeutic strategies against these conditions are not available. In this study, we demonstrate that a human-origin Lactobacillus paracasei D3-5 strain (D3-5), even in the non-viable form, extends life span of Caenorhabditis elegans. In addition, feeding of heat-killed D3-5 to old mice (> 79 weeks) prevents high- fat diet-induced metabolic dysfunctions, decreases leaky gut and inflammation, and improves physical and cognitive functions. D3-5 feeding significantly increases mucin production, and proportionately, the abundance of mucin-degrading bacteria Akkermansia muciniphila also increases. Mechanistically, we show that the lipoteichoic acid (LTA), a cell wall component of D3-5, enhances mucin (Muc2) expression by modulating TLR-2/p38-MAPK/NF-kB pathway, which in turn reduces age-related leaky gut and inflammation. The findings indicate that the D3-5 and its LTA can prevent/treat age-related leaky gut and inflammation.

KEYWORDS:

Aging; Cell wall; Cognition; Goblet cell; Inflammation; Leaky gut; Lipoteichoic acid; Metabolism; Mucin; Physical function; Probiotics

PMID:
31814084
DOI:
10.1007/s11357-019-00137-4

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