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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 7

Taurine significantly decreases epithelial permeability, increases tight junction proteins, reduces fat accumulation, and reduces gut leakiness in C. elegans.

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Taurine significantly decreases epithelial permeability, increases tight...
(A–C) Taurine supplementation in cecal conditioned media (CCM) in control significantly reduced changes in TEER of Caco-2 cells monolayer (A) and significantly increased expression of tight junction protein Zo1 (B) and Ocln (C) expression. Values are mean of 2–3 repeated experiments done in triplicate. (D) Taurine treatment increased the life span of C. elegans. Kaplan-Meier curves were generated using survival data in days for each worm (n = 150–195 worms in each group), and statistical significance was calculated using the log-rank test. (E) Composite image of multiple worms. (F and G) Taurine treatment also increased physical activity (F) and intestinal permeability (leaky gut) using Smurf assay (G) in n = 120-150 worms in each group. Values are mean of 2–3 trials of cell culture experiments done in triplicate (A–C) and n = 120-195 worms (D–G). Data are shown as mean ± SEM. *P < 0.05, **P < 0.01 by 2-way ANOVA with Bonferroni’s corrections (A), Student’s t test (B, C, F, G), and log-rank (D).

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