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A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis
Shokouh Ahmadi, Shaohua Wang, Ravinder Nagpal, Bo Wang, Shalini Jain, Atefeh Razazan, Sidharth P. Mishra, Xuewei Zhu, Zhan Wang, Kylie Kavanagh, Hariom Yadav
Shokouh Ahmadi, Shaohua Wang, Ravinder Nagpal, Bo Wang, Shalini Jain, Atefeh Razazan, Sidharth P. Mishra, Xuewei Zhu, Zhan Wang, Kylie Kavanagh, Hariom Yadav
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Research Article Gastroenterology Microbiology

A human-origin probiotic cocktail ameliorates aging-related leaky gut and inflammation via modulating the microbiota/taurine/tight junction axis

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Abstract

Inflammation is a major risk factor of morbidity and mortality in older adults. Although its precise etiology is unknown, low-grade inflammation in older adults is commonly associated with increased intestinal epithelial permeability (leaky gut) and abnormal (dysbiotic) gut microbiota. The increasing older population and lack of treatments to reduce aging-related microbiota dysbiosis, leaky gut, and inflammation culminates in a rise in aging-related comorbidities, constituting a significant public health concern. Here, we demonstrate that a human-origin probiotic cocktail containing 5 Lactobacillus and 5 Enterococcus strains isolated from healthy infant gut prevented high-fat diet–induced (HFD-induced) microbiota dysbiosis, leaky gut, inflammation, metabolic dysfunctions, and physical function decline in older mice. Probiotic-modulated gut microbiota primarily reduced leaky gut by increasing tight junctions, which in turn reduced inflammation. Mechanistically, probiotics modulated microbiota in a way to increase bile salt hydrolase activity, which in turn increased taurine abundance in the gut that stimulated tight junctions and suppressed gut leakiness. Furthermore, in Caenorhabditis elegans, taurine increased life span, reduced adiposity and leaky gut, and enhanced physical function. The results suggest that such probiotic therapies could prevent or treat aging-related leaky gut and inflammation in the elderly.

Authors

Shokouh Ahmadi, Shaohua Wang, Ravinder Nagpal, Bo Wang, Shalini Jain, Atefeh Razazan, Sidharth P. Mishra, Xuewei Zhu, Zhan Wang, Kylie Kavanagh, Hariom Yadav

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Figure 6

Probiotic therapy modulates gut metabolome and increases taurine production by enhancing bile salt hydrolase (BSH) activity in the gut of older HFD-fed mice.

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Probiotic therapy modulates gut metabolome and increases taurine product...
(A–C) Untargeted-unbiased metabolomics analyses show that the production of distinct metabolites shown by principal component analysis (PCA) (A), group clustering (B), and fold change abundance enrichment (C) were significantly changed in probiotic-fed old mice (n = 5) compared with their controls (n = 5). (D) Similarly, metabolite heatmap shows differential clusters that are significantly changed in probiotic-fed older mice feces compared with controls. (E–I) Abundance of taurine (E) and total bile acids (F), glucose (G), butyrate (H) and propionate (I) was significantly increased in the feces of probiotic-fed older mice (n = 5) compared with their controls (n = 5). (H) Probiotics feeding significantly enhanced bile salt hydrolase (BSH) activity in the gut of older mice. Values are mean of n = 5 control and n = 5 probiotics group, and data are shown as mean ± SEM. **P < 0.01 and ***P < 0.001. PLS-tool box in MatLab (A and B) and Welch t-test (E–J) were used.

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