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

被引:140
作者
Wang, Shaohua [1 ]
Ahmadi, Shokouh [1 ]
Nagpal, Ravinder [1 ]
Jain, Shalini [3 ,4 ]
Mishra, Sidharth P. [1 ]
Kavanagh, Kylie [1 ,5 ,8 ]
Zhu, Xuewei [1 ,2 ]
Wang, Zhan [1 ]
McClain, Donald A. [3 ,4 ]
Kritchevsky, Stephen B. [6 ]
Kitzman, Dalane W. [6 ,7 ]
Yadav, Hariom [1 ,2 ]
机构
[1] Wake Forest Sch Med, Dept Internal Med Mol Med, Winston Salem, NC 27101 USA
[2] Wake Forest Sch Med, Dept Microbiol & Immunol, Winston Salem, NC 27101 USA
[3] Wake Forest Sch Med, Dept Endocrinol & Metab, Winston Salem, NC 27101 USA
[4] Wake Forest Sch Med, Mouse Metab Phenotyping Core, Winston Salem, NC 27101 USA
[5] Wake Forest Sch Med, Dept Pathol Comparat Med, Winston Salem, NC 27101 USA
[6] Wake Forest Sch Med, Dept Gerontol & Geriatr Med, Winston Salem, NC 27101 USA
[7] Wake Forest Sch Med, Dept Cardiol, Winston Salem, NC 27101 USA
[8] Univ Tasmania, Biomed Sci, Hobart, Tas, Australia
基金
美国国家卫生研究院;
关键词
Aging; Cell wall; Cognition; Goblet cell; Inflammation; Leaky gut; Lipoteichoic acid; Metabolism; Mucin; Probiotics; Physical function; AKKERMANSIA-MUCINIPHILA; INSULIN SENSITIVITY; PROBIOTICS; MICROBIOTA; MUCUS; RECOGNITION; ASSOCIATION; BACTERIA; DEFENSE; OBESITY;
D O I
10.1007/s11357-019-00137-4
中图分类号
R592 [老年病学]; C [社会科学总论];
学科分类号
03 ; 0303 ; 100203 ;
摘要
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.
引用
收藏
页码:333 / 352
页数:20
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