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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 4

Probiotics treatment increases expression of tight junctions in the intestine of older obese mice.

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Probiotics treatment increases expression of tight junctions in the inte...
(A and B) The mRNA expression of tight junction proteins like Zonulin-1 (Zo1) (A) and Occludin (Ocln) (B) were significantly increased in colon of probiotics fed older mice (n = 8) compared with their controls (n = 6). (C and D) Western blot analysis shows that Zo1 protein expression was significantly increased, while Ocln showed marginal increase in the colon tissues of probiotic-treated older mice (n = 7) compared with their controls (n = 6). (E and F) Global gene expression using RNAseq analysis revealed that probiotic feeding significantly increased around 856 genes while it decreased 1053 genes that were distinctly clustered in the probiotic-treated (n = 7) group versus controls (n = 6). (G) Pathway analysis of deferentially expressed genes (DEGs) shows that cell adhesion and cytokine (immune) pathways were more affected by probiotics treatment compared with their controls. Values are mean of n = 6–7 each group, and data are shown as mean ± SEM. **P < 0.01 and ***P < 0.001. Student t test (A, B, D) and random forest analysis (E) were used, as well as hierarchical clustering between samples using hclust, with diagrams drawn with ggplot2 (F) and differential expression of genes (DEGs) (G) were completed using R programs.

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