Gut Akkermansia muciniphila ameliorates metabolic dysfunction-associated fatty liver disease by regulating the metabolism of L-aspartate via gut-liver axis.
TL;DR: Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-association as discussed by the authors.
Abstract: The gut bacterium Akkermansia muciniphila has been increasingly recognized for its therapeutic potential in treating metabolic disorders, including obesity, diabetes, and metabolicdysfunction-assoc...
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TL;DR: The up-to-date information of gut microbiome dysbiosis and metabolomic changes along the stages of steatosis, NASH, fibrosis, and NAFLD-HCC is summarized.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is considered as one of the most prevalent chronic liver diseases worldwide due to the rapidly rising prevalence of obesity and metabolic syndrome. As a hepatic manifestation of metabolic disease, NAFLD begins with hepatic fat accumulation and progresses to hepatic inflammation, termed as non-alcoholic steatohepatitis (NASH), hepatic fibrosis/cirrhosis, and finally leading to NAFLD-related hepatocellular carcinoma (NAFLD-HCC). Accumulating evidence showed that the gut microbiome plays a vital role in the initiation and progression of NAFLD through the gut–liver axis. The gut–liver axis is the mutual communication between gut and liver comprising the portal circulation, bile duct, and systematic circulation. The gut microbiome dysbiosis contributes to NAFLD development by dysregulating the gut–liver axis, leading to increased intestinal permeability and unrestrained transfer of microbial metabolites into the liver. In this review, we systematically summarized the up-to-date information of gut microbiome dysbiosis and metabolomic changes along the stages of steatosis, NASH, fibrosis, and NAFLD-HCC. The components and functions of the gut–liver axis and its association with NAFLD were then discussed. In addition, we highlighted current knowledge of gut microbiome-based treatment strategies targeting the gut–liver axis for preventing NAFLD and its associated HCC.
25 citations
TL;DR: In this paper , the authors discuss the potential mechanisms by which the gut microbiota reduces cholesterol levels and sketch the application of probiotics from the genera Lactobacillus and Bifidobacterium in reducing cholesterol levels in clinical studies.
20 citations
TL;DR: The molecular, mechanistic effects of A. muciniphila in host health are evaluated and some of the missing links to be connected are suggested before the organism should be considered as a next-generation biotherapeutic agent.
Abstract: ABSTRACT Despite a short history since its first isolation, Akkermansia muciniphila has been extensively studied in relation to its effects on human metabolism. A recent human intervention study also demonstrated that the bacterium is safe to use for therapeutic purposes. The best-known effects of A. muciniphila in human health and disease relate to its ability to strengthen gut integrity, modulate insulin resistance, and protect the host from metabolic inflammation. A further molecular mechanism, induction of GLP-1 secretion through ICAM-2 receptor, was recently discovered with the identification of a new bacterial protein produced by A. muciniphila. However, other studies have suggested a detrimental role for A. muciniphila in specific host immune settings. Here, we evaluate the molecular, mechanistic effects of A. muciniphila in host health and suggest some of the missing links to be connected before the organism should be considered as a next-generation biotherapeutic agent.
16 citations
TL;DR: These findings provide the first data revealing that an MFD drives neonate gut microbiota development and ameliorates the colonic inflammation by regulating the gut microbiota.
Abstract: ABSTRACT The neonatal intestinal tract is immature and can be easily infected by pathogens causing inflammation. Maternal diet manipulation is a promising nutritional strategy to enhance the gut health of offspring. A fermented diet is a gut microbiota targeting diet containing live probiotics and their metabolites, which benefit the gut and overall health host. However, it remains unclear how a maternal fermented diet (MFD) affects neonatal intestinal inflammation. Here, in vivo and in vitro models together with multi-omics analysis were applied to investigate the impacts and the underlying mechanism through which an MFD prevents from gut inflammation in neonates. An MFD remarkably improved the performance of both sows and piglets and significantly altered the gut microbiome and milk metabolome of sows. In addition, the MFD significantly accelerated the maturation of the gut microbiota of neonates and increased the abundance of gut Lactobacillus and the microbial functions of amino acid-related enzymes and glucose metabolism on the weaning day. Notably, the MFD reduced susceptibility to colonic inflammation in offspring. The fecal microbiota of sows was then transplanted into mouse dams and it was found that the mouse dams and pups in the MFD group alleviated the LPS-induced decrease in gut Lactobacillus abundance and barrier injury. Milk L-glutamine (GLN) and gut Lactobacillus reuteri (LR) were found as two of the main MFD-induced sow effectors that contributed to the gut health of piglets. The properties of LR and GLN in modulating gut microbiota and alleviating colonic inflammation by inhibiting the phosphorylation of p38 and JNK activation of Caspase 3 were further verified. These findings provide the first data revealing that an MFD drives neonate gut microbiota development and ameliorates the colonic inflammation by regulating the gut microbiota. This fundamental evidence might provide references for modulating maternal nutrition to enhance early-life gut health and prevent gut inflammation. Graphical abstract
14 citations
TL;DR: The aims of this review are to summarize the roles of potential native and engineered probiotics in oncology, inflammatory bowel disease, and obesity, discussing the therapeutic applications of these probiotics.
Abstract: Intestinal homeostasis is a dynamic balance involving the interaction between the host intestinal mucosa, immune barrier, intestinal microecology, nutrients, and metabolites. Once homeostasis is out of balance, it will increase the risk of intestinal diseases and is also closely associated with some systemic diseases. Probiotics (Escherichia coli Nissle 1917, Akkermansia muciniphila, Clostridium butyricum, lactic acid bacteria and Bifidobacterium spp.), maintaining the gut homeostasis through direct interaction with the intestine, can also exist as a specific agent to prevent, alleviate, or cure intestinal-related diseases. With genetic engineering technology advancing, probiotics can also show targeted therapeutic properties. The aims of this review are to summarize the roles of potential native and engineered probiotics in oncology, inflammatory bowel disease, and obesity, discussing the therapeutic applications of these probiotics.
14 citations
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TL;DR: Timmomatic is developed as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data and is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested.
Abstract: Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data.
Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested.
Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic
Contact: ed.nehcaa-htwr.1oib@ledasu
Supplementary information: Supplementary data are available at Bioinformatics online.
39,291 citations
TL;DR: Substantial insight is provided into the intricate mechanisms of bacterial regulation of the cross-talk between the host and gut microbiota and provides a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
Abstract: Obesity and type 2 diabetes are characterized by altered gut microbiota, inflammation, and gut barrier disruption. Microbial composition and the mechanisms of interaction with the host that affect gut barrier function during obesity and type 2 diabetes have not been elucidated. We recently isolated Akkermansia muciniphila, which is a mucin-degrading bacterium that resides in the mucus layer. The presence of this bacterium inversely correlates with body weight in rodents and humans. However, the precise physiological roles played by this bacterium during obesity and metabolic disorders are unknown. This study demonstrated that the abundance of A. muciniphila decreased in obese and type 2 diabetic mice. We also observed that prebiotic feeding normalized A. muciniphila abundance, which correlated with an improved metabolic profile. In addition, we demonstrated that A. muciniphila treatment reversed high-fat diet-induced metabolic disorders, including fat-mass gain, metabolic endotoxemia, adipose tissue inflammation, and insulin resistance. A. muciniphila administration increased the intestinal levels of endocannabinoids that control inflammation, the gut barrier, and gut peptide secretion. Finally, we demonstrated that all these effects required viable A. muciniphila because treatment with heat-killed cells did not improve the metabolic profile or the mucus layer thickness. In summary, this study provides substantial insight into the intricate mechanisms of bacterial (i.e., A. muciniphila) regulation of the cross-talk between the host and gut microbiota. These results also provide a rationale for the development of a treatment that uses this human mucus colonizer for the prevention or treatment of obesity and its associated metabolic disorders.
3,263 citations
TL;DR: Understanding of pathogenic mechanisms and clinical features of NAFLD is driving progress in therapeutic strategies now in clinical trials and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression are discussed.
Abstract: There has been a rise in the prevalence of nonalcoholic fatty liver disease (NAFLD), paralleling a worldwide increase in diabetes and metabolic syndrome. NAFLD, a continuum of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), has a variable course but can lead to cirrhosis and liver cancer. Here we review the pathogenic and clinical features of NAFLD, its major comorbidities, clinical progression and risk of complications and in vitro and animal models of NAFLD enabling refinement of therapeutic targets that can accelerate drug development. We also discuss evolving principles of clinical trial design to evaluate drug efficacy and the emerging targets for drug development that involve either single agents or combination therapies intended to arrest or reverse disease progression.
2,004 citations
TL;DR: The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al.
Abstract: The following guidelines are excerpted (as permitted under the Creative Commons Attribution License (CCAL), with the knowledge and approval of PLoS Biology and the authors) from Kilkenny et al (2010).
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1,916 citations
TL;DR: A narrative review focuses on the rapidly expanding body of clinical evidence that supports the concept of NAFLD as a multisystem disease and the factors linkingNAFLD with other extra-hepatic chronic diseases, such as T2DM, CVD, cardiac diseases and CKD.
1,897 citations