scholarly journals Liver Steatosis, Gut-Liver Axis, Microbiome and Environmental Factors. A Never-Ending Bidirectional Cross-Talk

2020 ◽  
Vol 9 (8) ◽  
pp. 2648 ◽  
Author(s):  
Agostino Di Ciaula ◽  
Jacek Baj ◽  
Gabriella Garruti ◽  
Giuseppe Celano ◽  
Maria De Angelis ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiota ◽  
Intestinal Permeability ◽  
Immune Cells ◽  
Critical Role ◽  
Liver Steatosis ◽  
Food Contaminants ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver ◽  
Molecular Patterns

The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide and parallels comorbidities such as obesity, metabolic syndrome, dyslipidemia, and diabetes. Recent studies describe the presence of NAFLD in non-obese individuals, with mechanisms partially independent from excessive caloric intake. Increasing evidences, in particular, point towards a close interaction between dietary and environmental factors (including food contaminants), gut, blood flow, and liver metabolism, with pathways involving intestinal permeability, the composition of gut microbiota, bacterial products, immunity, local, and systemic inflammation. These factors play a critical role in the maintenance of intestinal, liver, and metabolic homeostasis. An anomalous or imbalanced gut microbial composition may favor an increased intestinal permeability, predisposing to portal translocation of microorganisms, microbial products, and cell wall components. These components form microbial-associated molecular patterns (MAMPs) or pathogen-associated molecular patterns (PAMPs), with potentials to interact in the intestine lamina propria enriched in immune cells, and in the liver at the level of the immune cells, i.e., Kupffer cells and stellate cells. The resulting inflammatory environment ultimately leads to liver fibrosis with potentials to progression towards necrotic and fibrotic changes, cirrhosis. and hepatocellular carcinoma. By contrast, measures able to modulate the composition of gut microbiota and to preserve gut vascular barrier might prevent or reverse NAFLD.

scholarly journals Insights into the Impact of Microbiota in the Treatment of NAFLD/NASH and Its Potential as a Biomarker for Prognosis and Diagnosis

Biomedicines ◽  
2021 ◽  
Vol 9 (2) ◽  
pp. 145
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solis-Urra ◽  
Jerónimo Aragón-Vela ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Fecal Microbiota Transplantation ◽  
Liver Steatosis ◽  
Intestinal Barrier ◽  
Fecal Microbiota ◽  
Current Treatment ◽  
Immune Defense ◽  
Alcoholic Fatty Liver ◽  
The Impact

Non-alcoholic fatty liver disease (NAFLD) is an increasing cause of chronic liver illness associated with obesity and metabolic disorders, such as hypertension, dyslipidemia, or type 2 diabetes mellitus. A more severe type of NAFLD, non-alcoholic steatohepatitis (NASH), is considered an ongoing global health threat and dramatically increases the risks of cirrhosis, liver failure, and hepatocellular carcinoma. Several reports have demonstrated that liver steatosis is associated with the elevation of certain clinical and biochemical markers but with low predictive potential. In addition, current imaging methods are inaccurate and inadequate for quantification of liver steatosis and do not distinguish clearly between the microvesicular and the macrovesicular types. On the other hand, an unhealthy status usually presents an altered gut microbiota, associated with the loss of its functions. Indeed, NAFLD pathophysiology has been linked to lower microbial diversity and a weakened intestinal barrier, exposing the host to bacterial components and stimulating pathways of immune defense and inflammation via toll-like receptor signaling. Moreover, this activation of inflammation in hepatocytes induces progression from simple steatosis to NASH. In the present review, we aim to: (a) summarize studies on both human and animals addressed to determine the impact of alterations in gut microbiota in NASH; (b) evaluate the potential role of such alterations as biomarkers for prognosis and diagnosis of this disorder; and (c) discuss the involvement of microbiota in the current treatment for NAFLD/NASH (i.e., bariatric surgery, physical exercise and lifestyle, diet, probiotics and prebiotics, and fecal microbiota transplantation).

scholarly journals The Combination of Berberine, Tocotrienols and Coffee Extracts Improves Metabolic Profile and Liver Steatosis by the Modulation of Gut Microbiota and Hepatic miR-122 and miR-34a Expression in Mice

Nutrients ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 1281
Author(s):  
Valentina Cossiga ◽  
Vincenzo Lembo ◽  
Cecilia Nigro ◽  
Paola Mirra ◽  
Claudia Miele ◽  
...  
Keyword(s):  
Hepatic Steatosis ◽  
Plant Extracts ◽  
Elaeis Guineensis ◽  
Low Density Lipoprotein ◽  
Liver Steatosis ◽  
Density Lipoprotein ◽  
Coffea Canephora ◽  
Standard Diet ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver

Non-alcoholic-fatty liver disease (NAFLD) is spreading worldwide. Specific drugs for NAFLD are not yet available, even if some plant extracts show beneficial properties. We evaluated the effects of a combination, composed by Berberis Aristata, Elaeis Guineensis and Coffea Canephora, on the development of obesity, hepatic steatosis, insulin-resistance and on the modulation of hepatic microRNAs (miRNA) levels and microbiota composition in a mouse model of liver damage. C57BL/6 mice were fed with standard diet (SD, n = 8), high fat diet (HFD, n = 8) or HFD plus plant extracts (HFD+E, n = 8) for 24 weeks. Liver expression of miR-122 and miR-34a was evaluated by quantitativePCR. Microbiome analysis was performed on cecal content by 16S rRNA sequencing. HFD+E-mice showed lower body weight (p < 0.01), amelioration of insulin-sensitivity (p = 0.021), total cholesterol (p = 0.014), low-density-lipoprotein-cholesterol (p < 0.001), alanine-aminotransferase (p = 0.038) and hepatic steatosis compared to HFD-mice. While a decrease of hepatic miR-122 and increase of miR-34a were observed in HFD-mice compared to SD-mice, both these miRNAs had similar levels to SD-mice in HFD+E-mice. Moreover, a different microbial composition was found between SD- and HFD-mice, with a partial rescue of dysbiosis in HFD+E-mice. This combination of plant extracts had a beneficial effect on HFD-induced NAFLD by the modulation of miR-122, miR-34a and gut microbiome.

Interplay between early-life malnutrition, epigenetic modulation of the immune function and liver diseases

2019 ◽  
Vol 32 (1) ◽  
pp. 128-145 ◽  
Author(s):  
Sabrina Campisano ◽  
Anabela La Colla ◽  
Stella M. Echarte ◽  
Andrea N. Chisari
Keyword(s):  
Metabolic Syndrome ◽  
Immune System ◽  
Environmental Factors ◽  
Early Life ◽  
Critical Role ◽  
Later Life ◽  
Covalent Modification ◽  
Alcoholic Fatty Liver ◽  
The Metabolic Syndrome ◽  
Epigenetic Modulation

AbstractEarly-life nutrition plays a critical role in fetal growth and development. Food intake absence and excess are the two main types of energy malnutrition that predispose to the appearance of diseases in adulthood, according to the hypothesis of ‘developmental origins of health and disease’. Epidemiological data have shown an association between early-life malnutrition and the metabolic syndrome in later life. Evidence has also demonstrated that nutrition during this period of life can affect the development of the immune system through epigenetic mechanisms. Thus, epigenetics has an essential role in the complex interplay between environmental factors and genetics. Altogether, this leads to the inflammatory response that is commonly seen in non-alcoholic fatty liver disease (NAFLD), the hepatic manifestation of the metabolic syndrome. In conjunction, DNA methylation, covalent modification of histones and the expression of non-coding RNA are the epigenetic phenomena that affect inflammatory processes in the context of NAFLD. Here, we highlight current understanding of the mechanisms underlying developmental programming of NAFLD linked to epigenetic modulation of the immune system and environmental factors, such as malnutrition.

scholarly journals Molecular and Pathophysiological Links between Metabolic Disorders and Inflammatory Bowel Diseases

2021 ◽  
Vol 22 (17) ◽  
pp. 9139
Author(s):  
Chang-Kee Hyun
Keyword(s):  
Gut Microbiota ◽  
Inflammatory Bowel Diseases ◽  
Metabolic Disorders ◽  
Molecular Mechanisms ◽  
Pathological Feature ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver ◽  
Intestinal Immune System ◽  
Bowel Diseases ◽  
Inflammatory Bowel

Despite considerable epidemiological evidence indicating comorbidity between metabolic disorders, such as obesity, type 2 diabetes, and non-alcoholic fatty liver disease, and inflammatory bowel diseases (IBD), such as Crohn’s disease and ulcerative colitis, as well as common pathophysiological features shared by these two categories of diseases, the relationship between their pathogenesis at molecular levels are not well described. Intestinal barrier dysfunction is a characteristic pathological feature of IBD, which also plays causal roles in the pathogenesis of chronic inflammatory metabolic disorders. Increased intestinal permeability is associated with a pro-inflammatory response of the intestinal immune system, possibly leading to the development of both diseases. In addition, dysregulated interactions between the gut microbiota and the host immunity have been found to contribute to immune-mediated disorders including the two diseases. In connection with disrupted gut microbial composition, alterations in gut microbiota-derived metabolites have also been shown to be closely related to the pathogeneses of both diseases. Focusing on these prominent pathophysiological features observed in both metabolic disorders and IBD, this review highlights and summarizes the molecular risk factors that may link between the pathogeneses of the two diseases, which is aimed at providing a comprehensive understanding of molecular mechanisms underlying their comorbidity.

scholarly journals The Effects of Gelatinized Wheat Starch and High Salt Diet on Gut Microbiota and Metabolic Disorder

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 301 ◽  
Author(s):  
Moon Ho Do ◽  
Hye-Bin Lee ◽  
Eunjung Lee ◽  
Ho-Young Park
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Normal Diet ◽  
Wheat Starch ◽  
Microbial Composition ◽  
Alcoholic Fatty Liver ◽  
Gelatinized Starch ◽  
The Difference ◽  
Related Proteins ◽  
Starch Diet

Diets high in gelatinized starch and high in gelatinized starch supplemented with salt-induced metabolic disorders and changes in gut microbiota have scarcely been studied. In this study, mice on wheat starch diets (WD) exhibited significantly higher body weight, white adipose tissue (WAT), and gut permeability compared to those on normal diet (ND). However, gelatinized wheat starch diet (GWD) and NaCl-supplemented gelatinized wheat starch diet (SGW) mice did not increase body and WAT weights or dyslipidemia, and maintained consistent colon pH at ND levels. WD mice showed higher levels of Desulfovibrio, Faecalibaculum, and Lactobacillus and lower levels of Muribaculum compared to ND mice. However, GWD and SGW mice showed a significantly different gut microbial composition, such as a lower proportion of Lactobacillus and Desulfovibrio, and higher proportion of Faecalibaculum and Muribaculum compared to WD mice. High starch diet-induced dysbiosis caused increase of lipid accumulation and inflammation-related proteins’ expression, thereby leading to non-alcoholic fatty liver disease. However, GWD and SGW showed lower levels than that, and it might be due to the difference in the gut microbial composition compared to WD. Taken together, diets high in gelatinized starch and high in gelatinized starch supplemented with salt induced mild metabolic disorders compared to native starch.

scholarly journals Gut Microbiota: A Key Regulator in the Effects of Environmental Hazards on Modulates Insulin Resistance

2022 ◽  
Vol 11 ◽  
Author(s):  
Ruixue Huang
Keyword(s):  
Insulin Resistance ◽  
Environmental Factors ◽  
Gut Microbiota ◽  
Health Effect ◽  
Critical Role ◽  
Environmental Hazards ◽  
Baseline Drift ◽  
Short Period ◽  
Drift Theory

Insulin resistance is a hallmark of Alzheimer’s disease (AD), type II diabetes (T2D), and Parkinson’s disease (PD). Emerging evidence indicates that these disorders are typically characterized by alterations in the gut microbiota composition, diversity, and their metabolites. Currently, it is understood that environmental hazards including ionizing radiation, toxic heavy metals, pesticides, particle matter, and polycyclic aromatic hydrocarbons are capable of interacting with gut microbiota and have a non-beneficial health effect. Based on the current study, we propose the hypothesis of “gut microenvironment baseline drift”. According to this “baseline drift” theory, gut microbiota is a temporarily combined cluster of species sharing the same environmental stresses for a short period, which would change quickly under the influence of different environmental factors. This indicates that the microbial species in the gut do not have a long-term relationship; any split, division, or recombination may occur in different environments. Nonetheless, the “baseline drift” theory considers the critical role of the response of the whole gut microbiome. Undoubtedly, this hypothesis implies that the gut microbiota response is not merely a “cross junction” switch; in contrast, the human health or disease is a result of a rich palette of gut-microbiota-driven multiple-pathway responses. In summary, environmental factors, including hazardous and normal factors, are critical to the biological impact of the gut microbiota responses and the dual effect of the gut microbiota on the regulation of biological functions. Novel appreciation of the role of gut microbiota and environmental hazards in the insulin resistance would shed new light on insulin resistance and also promote the development of new research direction and new overcoming strategies for patients.

scholarly journals Reduced obesity, diabetes, and steatosis upon cinnamon and grape pomace are associated with changes in gut microbiota and markers of gut barrier

2018 ◽  
Vol 314 (4) ◽  
pp. E334-E352 ◽  
Author(s):  
Matthias Van Hul ◽  
Lucie Geurts ◽  
Hubert Plovier ◽  
Céline Druart ◽  
Amandine Everard ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
High Fat Diet ◽  
Metabolic Profile ◽  
Liver Steatosis ◽  
Grape Pomace ◽  
Metabolic Effects ◽  
High Fat ◽  
Gut Barrier ◽  
Microbial Composition ◽  
Gut Barrier Function

Increasing evidence suggests that polyphenols have a significant potential in the prevention and treatment of risk factors associated with metabolic syndrome. The objective of this study was to assess the metabolic outcomes of two polyphenol-containing extracts from cinnamon bark (CBE) and grape pomace (GPE) on C57BL/6J mice fed a high-fat diet (HFD) for 8 wk. Both CBE and GPE were able to decrease fat mass gain and adipose tissue inflammation in mice fed a HFD without reducing food intake. This was associated with reduced liver steatosis and lower plasma nonesterified fatty acid levels. We also observed a beneficial effect on glucose homeostasis, as evidenced by an improved glucose tolerance and a lower insulin resistance index. These ameliorations of the overall metabolic profile were associated with a significant impact on the microbial composition, which was more profound for the GPE than for the CBE. At the genus level, Peptococcus were decreased in the CBE group. In the GPE-treated group, several key genera that have been previously found to be linked with HFD, metabolic effects, and gut barrier integrity were affected: we observed a decrease of Desulfovibrio, Lactococcus, whereas Allobaculum and Roseburia were increased. In addition, the expression of several antimicrobial peptides and tight junction proteins was increased in response to both CBE and GPE supplementation, indicating an improvement of the gut barrier function. Collectively, these data suggest that CBE and GPE can ameliorate the overall metabolic profile of mice on a high-fat diet, partly by acting on the gut microbiota.

scholarly journals Critical Role of Gut Microbiota and Epigenetic Factors in the Pathogenesis of Behçet’s Disease

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaomin Ma ◽  
Xin Wang ◽  
Guangbing Zheng ◽  
Guiqin Tan ◽  
Fangyu Zhou ◽  
...  
Keyword(s):  
Environmental Factors ◽  
Gut Microbiota ◽  
Behçet’S Disease ◽  
Behcet’S Disease ◽  
Behçet's Disease ◽  
Epigenetic Modification ◽  
Critical Role ◽  
The Body ◽  
Epigenetic Factors ◽  
Behcet's Disease

Behçet’s disease (BD) is a chronic refractory multisystem autoinflammatory disease, characterized by typical clinical features of non-specific vasculitis, oral and genital ulcers, uveitis, as well as skin lesions. The exact etiopathogenesis of BD remains unknown, existing studies have indicated that genetics and environmental factors contribute to the increased development of BD. Recently, several studies have shown that external environmental factors can affect the process of epigenetic modification, and abnormalities of epigenetic factors have been confirmed to be involved in the occurrence of BD. At the same time, abnormalities of gut microbiota (GM) in the body, have also been confirmed to participate in the pathogenesis of BD by regulating the balance of Th17/Tregs. This article reviews the pathogenesis of BD and summarizes numerous clinical studies, focusing on the mechanism of GM and epigenetic factors impacting on BD, and providing new ideas for further elucidating the pathogenesis of BD.

scholarly journals Bifidobacterium adolescentis Alleviates Liver Steatosis and Steatohepatitis by Increasing Fibroblast Growth Factor 21 Sensitivity

2021 ◽  
Vol 12 ◽  
Author(s):  
Xiaoxue Long ◽  
Dan Liu ◽  
Qiongmei Gao ◽  
Jiacheng Ni ◽  
Lingling Qian ◽  
...  
Keyword(s):  
Growth Factor ◽  
Gut Microbiota ◽  
Fibroblast Growth Factor ◽  
Liver Steatosis ◽  
Fibroblast Growth Factor 21 ◽  
Dependent Manner ◽  
Fibroblast Growth ◽  
Bifidobacterium Adolescentis ◽  
Alcoholic Fatty Liver ◽  
Response Test

The gut microbiota is a newly identified contributor to the development of non-alcoholic fatty liver disease (NAFLD). Previous studies of Bifidobacterium adolescentis (B. adolescentis), a species of Bifidobacterium that is common in the human intestinal tract, have demonstrated that it can alleviate liver steatosis and steatohepatitis. Fibroblast growth factor 21 (FGF21) has long been considered as a biomarker of NAFLD, and recent studies have shown the protective effect of FGF21 analogs on NAFLD. We wondered whether B. adolescentis treatment would alleviate NAFLD via the interaction with FGF21. To this end, male C57BL/6J mice on a choline-deficient high-fat diet (CDHFD) were treated with drinking water supplemented with B. adolescentis for 8 weeks, followed by the acute administration of recombinant mouse FGF21 protein (rmFGF21) to conduct the FGF21 response test. Consistent with previous studies, B. adolescentis supplementation reversed the CDHFD-induced liver steatosis and steatohepatitis. This was evaluated on the NAFLD activity score (NAS), reduced liver enzymes, and lipid accumulation. Further studies demonstrated that B. adolescentis supplementation preserved the gut barrier, reduced the gut microbiota-derived lipopolysaccharide (LPS), and inhibited the hepatic TLR4/NF-κB pathway. This was accompanied by the elevated expressions of the receptors of FGF21, fibroblast growth factor receptor 1 (FGFR1) and β-klotho (KLB), in the liver and the decreased expression of FGF21. The results of FGF21 response test showed that B. adolescentis supplementation alleviated the CDHFD-induced FGF21 resistance. In vivo experiments suggested that LPS could suppress the expression of FGF21 and KLB in a dose-dependent manner. Collectively, this study showed that B. adolescentis supplementation could alleviate NAFLD by increasing FGF21 sensitivity.

scholarly journals Gut Microbiota and Immune System Interactions

2020 ◽  
Vol 8 (10) ◽  
pp. 1587 ◽  
Author(s):  
Ji Yoo ◽  
Maureen Groer ◽  
Samia Dutra ◽  
Anujit Sarkar ◽  
Daniel McSkimming
Keyword(s):  
Immune System ◽  
Gut Microbiota ◽  
Immune Cells ◽  
Defense Mechanism ◽  
Short Chain Fatty Acids ◽  
Gut Bacteria ◽  
Mucosal Barrier ◽  
Microbial Composition ◽  
Dynamic Interactions ◽  
Metabolic Products

Dynamic interactions between gut microbiota and a host’s innate and adaptive immune systems are essential in maintaining intestinal homeostasis and inhibiting inflammation. Gut microbiota metabolizes proteins and complex carbohydrates, synthesizes vitamins, and produces an enormous number of metabolic products that can mediate cross-talk between gut epithelium and immune cells. As a defense mechanism, gut epithelial cells produce a mucosal barrier to segregate microbiota from host immune cells and reduce intestinal permeability. An impaired interaction between gut bacteria and the mucosal immune system can lead to an increased abundance of potentially pathogenic gram-negative bacteria and their associated metabolic changes, disrupting the epithelial barrier and increasing susceptibility to infections. Gut dysbiosis, or negative alterations in gut microbial composition, can also dysregulate immune responses, causing inflammation, oxidative stress, and insulin resistance. Over time, chronic dysbiosis and the leakage of microbiota and their metabolic products across the mucosal barrier may increase prevalence of type 2 diabetes, cardiovascular disease, autoimmune disease, inflammatory bowel disease, and a variety of cancers. In this paper, we highlight the pivotal role gut bacteria and their metabolic products (short-chain fatty acids (SCFAs)) which play in mucosal immunity.

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