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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 1

Probiotics feeding prevents HFD-induced metabolic dysfunctions in older mice.

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Probiotics feeding prevents HFD-induced metabolic dysfunctions in older ...
(A and B) Ten weeks of probiotics improved glucose tolerance and enhanced insulin sensitivity in older obese mice, measured by oral glucose tolerance test (A) and insulin tolerance test (B) (n = 6 in control and n = 8 in probiotics groups; *P < 0.05, 2-way ANOVA). (C) Representative images of H&E staining of liver (upper panels) showing reduced fat accumulation and white adipose tissue (WAT; lower panels) showing reduced adipocyte size, along with reduced inflammation (indicated by crown-like structures; red arrows) in probiotics fed mice (n = 8) compared with their controls (n = 6). (D) Crown-like structures are graphed. (E) Probiotic-fed older obese mice (n = 8) exhibited higher physical function presented as walking speed compared with their age- and sex-matched HFD-fed controls (n = 6). Values are mean of n = 6–8 mice in each group, and data are shown as mean ± SEM. *P < 0.05, and ***P < 0.001 by 2-way ANOVA with Bonferroni’s correction (A and B) and Student’s t test (D and E).

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