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. A human-origin probiotic cocktail improved metabolic dysfunction, gut microbiota, and taurine production, which increased tight junctions and reduced leaky gut and inflammation in older mice.

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Negative Effects of a High-Fat Diet on Intestinal Permeability: A Review

Michael Rohr, Chandrakala Narasimhulu, Trina Rudeski-Rohr … (2019)

The intestinal tract is the largest barrier between a person and the environment. In this role, the intestinal tract is responsible not only for absorbing essential dietary nutrients, but also for protecting the host from a variety of ingested toxins and microbes. The intestinal barrier system is composed of a mucus layer, intestinal epithelial cells (IECs), tight junctions (TJs), immune cells, and a gut microbiota, which are all susceptible to external factors such as dietary fats. When components of this barrier system are disrupted, intestinal permeability to luminal contents increases, which is implicated in intestinal pathologies such as inflammatory bowel disease, necrotizing enterocolitis, and celiac disease. Currently, there is mounting evidence that consumption of excess dietary fats can enhance intestinal permeability differentially. For example, dietary fat modulates the expression and distribution of TJs, stimulates a shift to barrier-disrupting hydrophobic bile acids, and even induces IEC oxidative stress and apoptosis. In addition, a high-fat diet (HFD) enhances intestinal permeability directly by stimulating proinflammatory signaling cascades and indirectly via increasing barrier-disrupting cytokines [TNFα, interleukin (IL) 1B, IL6, and interferon γ (IFNγ)] and decreasing barrier-forming cytokines (IL10, IL17, and IL22). Finally, an HFD negatively modulates the intestinal mucus composition and enriches the gut microflora with barrier-disrupting species. Although further research is necessary to understand the precise role HFDs play in intestinal permeability, current data suggest a stronger link between diet and intestinal disease than was first thought to exist. Therefore, this review seeks to highlight the various ways an HFD disrupts the gut barrier system and its many implications in human health.

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Review: Taurine: A “very essential” amino acid

Harris Ripps, Wen Shen (2012)

Taurine is an organic osmolyte involved in cell volume regulation, and provides a substrate for the formation of bile salts. It plays a role in the modulation of intracellular free calcium concentration, and although it is one of the few amino acids not incorporated into proteins, taurine is one of the most abundant amino acids in the brain, retina, muscle tissue, and organs throughout the body. Taurine serves a wide variety of functions in the central nervous system, from development to cytoprotection, and taurine deficiency is associated with cardiomyopathy, renal dysfunction, developmental abnormalities, and severe damage to retinal neurons. All ocular tissues contain taurine, and quantitative analysis of ocular tissue extracts of the rat eye revealed that taurine was the most abundant amino acid in the retina, vitreous, lens, cornea, iris, and ciliary body. In the retina, taurine is critical for photoreceptor development and acts as a cytoprotectant against stress-related neuronal damage and other pathological conditions. Despite its many functional properties, however, the cellular and biochemical mechanisms mediating the actions of taurine are not fully known. Nevertheless, considering its broad distribution, its many cytoprotective attributes, and its functional significance in cell development, nutrition, and survival, taurine is undoubtedly one of the most essential substances in the body. Interestingly, taurine satisfies many of the criteria considered essential for inclusion in the inventory of neurotransmitters, but evidence of a taurine-specific receptor has yet to be identified in the vertebrate nervous system. In this report, we present a broad overview of the functional properties of taurine, some of the consequences of taurine deficiency, and the results of studies in animal models suggesting that taurine may play a therapeutic role in the management of epilepsy and diabetes.

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Comparative Microbiome Signatures and Short-Chain Fatty Acids in Mouse, Rat, Non-human Primate, and Human Feces

Ravinder Nagpal, Shaohua WANG, Leah Solberg Woods … (2018)

Gut microbiome plays a fundamental role in several aspects of host health and diseases. There has been an exponential surge in the use of animal models that can mimic different phenotypes of the human intestinal ecosystem. However, data on host species-specific signatures of gut microbiome and its metabolites like short-chain fatty acids (SCFAs; i.e., acetate, propionate, and butyrate) and lactate in these models and their similarities/differences from humans remain limited, due to high variability in protocols and analyses. Here, we analyze the fecal microbiota composition and the fecal levels of SCFAs and lactate in three of the most-widely used animal models, i.e., mice, rats, and non-human primates (NHPs) and compare them with human subjects, using data generated on a single platform with same protocols. The data show several species-specific similarities and differences in the gut microbiota and fecal organic acids between these species groups. Based on β-diversity, the gut microbiota in humans seems to be closer to NHPs than to mice and rats; however, among rodents, mice microbiota appears to be closer to humans than rats. The phylum-level analyses demonstrate higher Firmicutes–Bacteroidetes ratio in humans and NHPs vs. mice and rats. Human microbiota is dominated by Bacteroides followed by Ruminococcaceae and Clostridiales. Mouse gut is predominated by members of the family S24-7 followed by those from the order Clostridiales, whereas rats and NHPs have higher abundance of Prevotella compared with mice and humans. Also, fecal levels of lactate are higher in mice and rats vs. NHPs and humans, while acetate is highest in human feces. These data of host species-specific gut microbiota signatures in some of the most widely used animal models in context to the human microbiota might reflect disparities in host factors, e.g., diets, genetic origin, gender and age, and hence call for prospective studies investigating the features of gut microbiome in such animal models by controlling for these host elements.