Gastric intestinal metaplasia (IM) is a precancerous lesion that increases the risk of subsequent gastric cancer (GC) development. Therefore, the mechanism of IM has been the focus of basic and clinical research. Helicobacter pylori (H. pylori) infection has been recognized as the main pathogenesis of gastric IM. However, more and more studies have shown that chronic inflammation of gastric mucosa caused by bile reflux is the key pathogenic factor of gastric IM. Bile reflux activates the expression of IM biomarkers via the bile acid receptor. In addition, microRNAs, exosomes, and epigenetics are also involved in the occurrence and development of bile acid-induced gastric IM. Currently, the relevant research is still very few. The molecular mechanism of the phenotypic transformation of gastrointestinal epithelial cells induced by bile acids has not been fully understood. This article mainly reviews the physiology and pathology of bile acid, mechanism of gastric IM induced by bile acid, bile acid receptors, and so on, in order to provide reference for further research. 

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Roles and action mechanisms of bile acid-induced gastric intestinal metaplasia: a review

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The global obesity epidemic particularly affects women of reproductive age. Offspring of obese mothers suffer from an increased risk of liver disease but the molecular mechanisms involved remain unknown. We performed an integrative genomic analysis of datasets that investigated the impact of maternal obesity on the hepatic gene expression profile of the offspring in mice. Furthermore, we developed a murine model of maternal obesity and studied the development of liver disease and the gene expression profile of the top dysregulated genes by quantitative real-time polymerase chain reaction (qPCR). Our data are available for interactive exploration on our companion webpage. We identified five publicly available datasets relevant to our research question. Pathways involved in metabolism, the innate immune system, the clotting cascade, and the cell cycle were consistently dysregulated in the offspring of obese mothers. Concerning genes involved in the development of liver disease, Egfr, Vegfb, Wnt2, Pparg and six other genes were dysregulated in multiple independent datasets. In our own model, we observed a higher tendency towards the development of non-alcoholic liver disease (60 vs. 20%) and higher levels of alanine aminotransferase (41.0 vs. 12.5 IU/l, p = 0.008) in female offspring of obese mothers. Male offspring presented higher levels of liver fibrosis (2.4 vs. 0.6% relative surface area, p = 0.045). In a qPCR gene expression analysis of our own samples, we found Fgf21, Pparg, Ppard, and Casp6 to be dysregulated by maternal obesity. Maternal obesity represents a looming threat to the liver health of future generations. Our comprehensive transcriptomic analysis will help to better understand the mechanisms of the development of liver disease in the offspring of obese mothers and can give rise to further explorations.

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Impact of Maternal Obesity on Liver Disease in the Offspring: A Comprehensive Transcriptomic Analysis and Confirmation of Results in a Murine Model

We investigated the alteration of gut microbiota and the associated metabolic risks in hypertensive patients with obstructive sleep apnea (OSA) comorbidity. Fecal and blood samples were collected from 52 hypertensive patients, who were divided into three groups: A (controls, apnea‐hypopnea index[AHI] < 5, n = 15), B (mild OSA, 5 < AHI < 20, n = 17), and C (moderate‐to‐severe OSA, AHI > 20, n = 20). The composition of the gut microbiota was studied through 16s RNA sequencing of variable regions 3–4. Analysis of the results revealed that group C had a significant higher concentration of total cholesterol, low‐density lipoprotein, and IL‐1β compared with group A. The Shannon index showed that bacterial biodiversity was lower in OSA patients. At the phylum level, the ratio of Firmicutes to Bacteroidetes (F/B) was significantly higher in group C than in groups A and B. At the genus level, the relative abundance of short‐chain fatty acids (SCFA)‐producing bacteria (e.g., Bacteroides and Prevotella) was lower while the number of inflammation‐related bacteria (e.g., Lactobacillus) was increased in patients with OSA. We found that the IL‐1β level was negatively correlated with Bacteroidetes. The area under the receiver operating characteristic curve was .672 for F/B ratio in determining hypertensive patients with OSA. In patients with hypertension, OSA was associated with worse gut dysbiosis, as evidenced by decreased levels of short‐chain fatty acids‐producing bacteria and increased number of inflammation‐related bacteria. The differences in gut microbiota discriminate hypertensive patients with OSA from those without and may result in an enhanced inflammatory response and increase the risk of metabolic diseases.

https://onlinelibrary.wiley.com/doi/pdfdirect/10.1111/jch.14598

Gut microbiota in hypertensive patients with versus without obstructive sleep apnea

Gut microbiota regulates essential processes of host metabolism and physiology: synthesis of vitamins, digestion of foods non-digestible by the host (such as fibers), and—most important—protects the digestive tract from pathogens. In this study, we focus on the CRISPR/Cas9 technology, which is extensively used to correct multiple diseases, including liver diseases. Then, we discuss the non-alcoholic fatty liver disease (NAFLD), affecting more than 25% of the global population; colorectal cancer (CRC) is second in mortality. We give space to rarely discussed topics, such as pathobionts and multiple mutations. Pathobionts help to understand the origin and complexity of the microbiota. Since several types of cancers have as target the gut, it is vital extending the research of multiple mutations to the type of cancers affecting the gut–liver axis.

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Microbiota–Liver Diseases Interactions

Obesity is becoming an increasing problem worldwide and is often, but not invariably, associated with dyslipidemia. The gut microbiota is increasingly linked to cardiovascular disease, nonalcoholic fatty liver disease, and type 2 diabetes mellitus. However, relatively little focus has been attributed to the role of gut-microbiota-derived metabolites in the development of dyslipidemia and alterations in lipid metabolism. In this review, we discuss current data involved in these processes and point out the therapeutic potentials. We cover the ability of gut microbiota metabolites to alter lipoprotein lipase action, VLDL secretion, and plasma triglyceride levels, and its effects on reverse cholesterol transport, adipocyte dysfunction, and adipose tissue inflammation. Finally, the current intervention strategies for treatment of obesity and dyslipidemia is addressed with emphasis on the role of gut microbiota metabolites and its ability to predict treatment efficacies.

Max S. Z. Zwartjes

Papers

The Role of Gut Microbiota and Its Produced Metabolites in Obesity, Dyslipidemia, Adipocyte Dysfunction, and Its Interventions.