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| Open AccessMatrix viscoelasticity promotes liver cancer progression in the pre-cirrhotic liver
Structural changes mediated by advanced glycation end-products enhance extracellular matrix viscoelasticity, and that viscoelasticity can promote cancer progression in vivo, independent of stiffness.
- Weiguo Fan
- , Kolade Adebowale
- & Natalie J. Török
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Article
| Open AccessReverse metabolomics for the discovery of chemical structures from humans
A new discovery strategy, ‘reverse metabolomics’, facilitates high-throughput matching of mass spectrometry spectra in public untargeted metabolomics datasets, and a proof-of-concept experiment identified an association between microbial bile amidates and inflammatory bowel disease.
- Emily C. Gentry
- , Stephanie L. Collins
- & Pieter C. Dorrestein
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Article |
Clonal haematopoiesis and risk of chronic liver disease
A study shows that clonal haematopoiesis of indeterminate potential is associated with an increased risk of chronic liver disease specifically through the promotion of liver inflammation and injury.
- Waihay J. Wong
- , Connor Emdin
- & Pradeep Natarajan
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Article |
Neuropeptide regulation of non-redundant ILC2 responses at barrier surfaces
The development of a new genetic tool to selectively deplete or modify group 2 innate lymphoid cells (ILC2s) addresses the debate regarding the non-redundant functions of this immune cell type.
- Amy M. Tsou
- , Hiroshi Yano
- & David Artis
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Article |
Identification of environmental factors that promote intestinal inflammation
The herbicide propyzamide increases inflammation in the small and large intestine, and the AHR–NF-κB–C/EBPβ signalling axis—which operates in T cells and dendritic cells to promote intestinal inflammation—is targeted by propyzamide.
- Liliana M. Sanmarco
- , Chun-Cheih Chao
- & Francisco J. Quintana
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Article |
Gut bacteria alleviate smoking-related NASH by degrading gut nicotine
Nicotine accumulates in the intestine during tobacco smoking and accelerates the progression of non-alcoholic fatty liver disease to non-alcoholic steatohepatitis (NASH), but it can be degraded effectively by the human symbiont Bacteroides xylanisolvens.
- Bo Chen
- , Lulu Sun
- & Changtao Jiang
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Article |
Discovery of bioactive microbial gene products in inflammatory bowel disease
A computational system termed MetaWIBELE (workflow to identify novel bioactive elements in the microbiome) is used to identify microbial gene products that are potentially bioactive and have a functional role in the pathogenesis of inflammatory bowel disease.
- Yancong Zhang
- , Amrisha Bhosle
- & Eric A. Franzosa
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Article |
Immune regulation by fungal strain diversity in inflammatory bowel disease
Genetically diverse Candida albicans strains in patients with inflammatory bowel disease secrete a toxin and aggravate IL-1β-dependent intestinal inflammation.
- Xin V. Li
- , Irina Leonardi
- & Iliyan D. Iliev
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Article |
Convergent somatic mutations in metabolism genes in chronic liver disease
Whole-genome sequencing analysis of somatic mutations in liver samples from patients with chronic liver disease identifies driver mutations in metabolism-related genes such as FOXO1, and shows that these variants frequently exhibit convergent evolution.
- Stanley W. K. Ng
- , Foad J. Rouhani
- & Peter J. Campbell
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Article
| Open AccessCells of the human intestinal tract mapped across space and time
Cells from embryonic, fetal, paediatric and adult human intestinal tissue are analysed at different locations along the intestinal tract to construct a single-cell atlas of the developing and adult human intestinal tract, encompassing all cell lineages.
- Rasa Elmentaite
- , Natsuhiko Kumasaka
- & Sarah A. Teichmann
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Article |
An organoid-based organ-repurposing approach to treat short bowel syndrome
In a rat model of short bowel syndrome, transplantation of small intestinal organoids into the colon partially restores intestinal function and improves survival—a proof of principle that organoid transplantation might have therapeutic benefit.
- Shinya Sugimoto
- , Eiji Kobayashi
- & Toshiro Sato
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Article |
Local immune response to food antigens drives meal-induced abdominal pain
In mice, oral tolerance to food antigens can break down after enteric infection, and this leads to food-induced pain resembling irritable bowel syndrome in humans.
- Javier Aguilera-Lizarraga
- , Morgane V. Florens
- & Guy E. Boeckxstaens
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Article |
Frequent mutations that converge on the NFKBIZ pathway in ulcerative colitis
In patients with ulcerative colitis, chronic inflammation can lead to remodelling of the colorectal epithelium through positive selection of clones with mutations in genes related to IL-17 signalling, which, however, might be negatively selected during colitis-associated carcinogenesis.
- Nobuyuki Kakiuchi
- , Kenichi Yoshida
- & Seishi Ogawa
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Article |
Bacteriophage targeting of gut bacterium attenuates alcoholic liver disease
In patients with alcoholic hepatitis, cytolysin-positive Enterococcus faecalis strains are correlated with liver disease severity and increased mortality, and in mouse models these strains can be specifically targeted by bacteriophages.
- Yi Duan
- , Cristina Llorente
- & Bernd Schnabl
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Article |
Resolving the fibrotic niche of human liver cirrhosis at single-cell level
Single-cell RNA sequencing is used to characterize and compare the functional diversity of cells from liver biopsies of human scarred and normal liver, and identifies markers for scar-associated macrophages and endothelial cells.
- P. Ramachandran
- , R. Dobie
- & N. C. Henderson
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Article |
Dynamics and genomic landscape of CD8+ T cells undergoing hepatic priming
CD8+ T cells that are primed by hepatocytes differentiate into dysfunctional T cells, which can be rescued by treatment with IL-2.
- Alexandre P. Bénéchet
- , Giorgia De Simone
- & Matteo Iannacone
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Article
| Open AccessMulti-omics of the gut microbial ecosystem in inflammatory bowel diseases
The Inflammatory Bowel Disease Multi’omics Database includes longitudinal data encompassing a multitude of analyses of stool, blood and biopsies of more than 100 individuals, and provides a comprehensive description of host and microbial activities in inflammatory bowel diseases.
- Jason Lloyd-Price
- , Cesar Arze
- & Curtis Huttenhower
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Article |
Colonic epithelial cell diversity in health and inflammatory bowel disease
Profiling of single epithelial cells in healthy and inflamed colons identifies specialized cellular subpopulations, including a type of goblet cell that secretes the antibacterial protein WFDC2, which preserves the integrity of the epithelial barrier layer.
- Kaushal Parikh
- , Agne Antanaviciute
- & Alison Simmons
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Letter |
Genomic insights into the 2016–2017 cholera epidemic in Yemen
Isolates of the Vibrio cholerae O1 serotype Ogawa from Yemen are from a single sublineage of the seventh pandemic El Tor (7PET) lineage and are susceptible to several commonly used antibiotics as well as to polymyxins.
- François-Xavier Weill
- , Daryl Domman
- & Marie-Laure Quilici
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Letter |
Moving beyond microbiome-wide associations to causal microbe identification
Triangulation of microbe–phenotype relationships is an effective method for reducing the noise inherent in microbiota studies and enabling identification of causal microbes of disease, which may be applicable to human microbiome studies.
- Neeraj K. Surana
- & Dennis L. Kasper
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Outline |
Fighting the fatty liver
Increased levels of obesity are driving an epidemic of non-alcoholic fatty liver disease. Understanding, diagnosing and treating this progressive condition are now priorities.
- Liam Drew
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Outline |
Fatty liver disease: turning the tide
A progressive and potentially life-threatening condition previously associated with alcoholism is becoming more common — even in non-drinkers.
- Liam Drew
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Letter |
Stromal R-spondin orchestrates gastric epithelial stem cells and gland homeostasis
Myofibroblast-derived R-spondin 3 orchestrates regeneration of antral stomach epithelium via Wnt signalling in Axin2+ stem cells.
- Michael Sigal
- , Catriona Y. Logan
- & Thomas F. Meyer
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Letter |
NAFLD causes selective CD4+ T lymphocyte loss and promotes hepatocarcinogenesis
Non-alcoholic fatty liver disease (NAFLD) is shown to promote hepatocellular carcinoma through the generation of linoleic acid, disruption of mitochondrial function and selective loss of CD4+ T cells, leading to impaired anti-tumour immunity.
- Chi Ma
- , Aparna H. Kesarwala
- & Tim F. Greten
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Article |
High-fat diet enhances stemness and tumorigenicity of intestinal progenitors
A high-fat diet increases the number of intestinal stem cells in mammals, both in vivo and in intestinal organoids; a pathway that involves PPAR-δ confers organoid-initiating capacity to non-stem cells and induces them to form in vivo tumours after loss of the Apc tumour suppressor.
- Semir Beyaz
- , Miyeko D. Mana
- & Ömer H. Yilmaz
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Letter |
Intestinal epithelial tuft cells initiate type 2 mucosal immunity to helminth parasites
Epithelial tuft cells secretion of IL-25 is shown to regulate type 2 epithelial responses to helminth parasite infection via an IL-13/IL-4Rα-dependent feedback loop.
- François Gerbe
- , Emmanuelle Sidot
- & Philippe Jay
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Letter |
Modelling human development and disease in pluripotent stem-cell-derived gastric organoids
The in vitro generation, from pluripotent stem cells, of three-dimensional human gastric organoids (hGOs) that contain a physiological gastric epithelium comprising both progenitor and differentiated cell types, and have expected functional characteristics is described, as is modelling the pathophysiological response of the human stomach to Helicobacter pylori using these hGOs.
- Kyle W. McCracken
- , Emily M. Catá
- & James M. Wells
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Outlook |
Public health: Society at large
The increasing prevalence of obesity is a worldwide phenomenon, affecting peoples from diverse cultural and economic backgrounds. By Tony Scully.
- Tony Scully
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Outlook |
Perspective: Tricks of the trade
Processed foods that dilute protein content subvert our appetite control systems, say Stephen J. Simpson and David Raubenheimer.
- Stephen J. Simpson
- & David Raubenheimer
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Outlook |
Perspective: Obesity is not a disease
The misguided urge to pathologize this condition reflects society's failure to come to terms with the need for prevention, says D. L. Katz.
- D. L. Katz
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Outlook |
Cell physiology: The changing colour of fat
The different functions of white, brown and beige fat might yield new targets in the fight against obesity and metabolic disease.
- Brian Owens
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Outlook |
Neuroscience: Dissecting appetite
A slew of new technologies are helping to map the neural circuits that control when, and how much, we eat.
- Bijal P. Trivedi
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Outlook |
Microbiome: A complicated relationship status
Nothing is simple about the links between the bacteria living in our guts and obesity.
- Sarah Deweerdt
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Outlook |
Heritability: The family roots of obesity
Scores of genes are implicated in obesity, but they cannot account for a family's predisposition to obesity. Are there other ways parents can influence their children?
- Cassandra Willyard
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Outlook |
Treatment: Marginal gains
Behavioural interventions work, but not for everyone, and weight regain is common. Are there better ways to treat obesity?
- Emily Anthes
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Letter |
Diet rapidly and reproducibly alters the human gut microbiome
Consuming diets rich in plant versus animal products changes the microbes found in the human gut within days, with important implications for our health and evolution.
- Lawrence A. David
- , Corinne F. Maurice
- & Peter J. Turnbaugh
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Letter |
Paneth cells as a site of origin for intestinal inflammation
Variation in ATG16L1, a protein involved in autophagy, confers risk for Crohn’s disease, but mice with hypomorphic ATG16L1 activity do not develop spontaneous intestinal inflammation; this study shows that autophagy compensates for endoplasmic reticulum stress — common in inflammatory bowel disease epithelium — specifically in Paneth cells, with Crohn’s-disease-like inflammation of the ileum originating from this cell type when both pathways are compromised.
- Timon E. Adolph
- , Michal F. Tomczak
- & Richard S. Blumberg
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Letter |
Adenoma-linked barrier defects and microbial products drive IL-23/IL-17-mediated tumour growth
In a mouse model of colorectal cancer, barrier deterioration results in adenoma invasion by microbial products that trigger tumour-elicited inflammation, which in turn drives IL-23-dependent tumour growth.
- Sergei I. Grivennikov
- , Kepeng Wang
- & Michael Karin
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Research Highlights |
Infection breaks truce
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Research Highlights |
Inflamed guts boost bad bacteria
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Letter |
ACE2 links amino acid malnutrition to microbial ecology and intestinal inflammation
Mutations in angiotensin-converting enzyme 2 are shown to predispose mice to colitis as a consequence of neutral amino acid malabsorption and a change in the resident microbiota; these results could explain how protein malnutrition — affecting up to one billion people — leads to intestinal inflammation.
- Tatsuo Hashimoto
- , Thomas Perlot
- & Josef M. Penninger
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News & Views |
Pinprick diagnostics
Rare tumour cells with mutations that confer drug resistance can go undetected by standard testing procedures, according to two studies, which show that such mutations can be detected in patients' blood. See Letters p.532 and p.537
- Eduardo Vilar
- & Josep Tabernero
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Letter |
Dietary-fat-induced taurocholic acid promotes pathobiont expansion and colitis in Il10−/− mice
Consumption of a diet high in milk-derived fat is shown to increase the abundance of sulphite-reducing bacteria by altering bile composition, leading to inflammation and colitis in genetically susceptible mice.
- Suzanne Devkota
- , Yunwei Wang
- & Eugene B. Chang
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News & Views |
One step closer to gut repair
The use of adult-tissue stem cells to treat gastrointestinal diseases holds much promise. A method for in vitro growth of gut stem cells and their use in repairing damaged intestines in mice has been described.
- Anisa Shaker
- & Deborah C. Rubin
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Letter |
The deubiquitinase USP9X suppresses pancreatic ductal adenocarcinoma
An in vivo transposon screen in a pancreatic cancer model identifies frequent inactivation of Usp9x; deletion of Usp9x cooperates with KrasG12D to accelerate rapidly pancreatic tumorigenesis in mice, validating their genetic interaction.
- Pedro A. Pérez-Mancera
- , Alistair G. Rust
- & David A. Tuveson
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Research Highlights |
Cell transplants repair colon
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Letter |
Goblet cells deliver luminal antigen to CD103+ dendritic cells in the small intestine
Goblet cells in the small intestine act as passages delivering small antigens to tolerance-inducing dendritic cells in the lamina propria.
- Jeremiah R. McDole
- , Leroy W. Wheeler
- & Mark J. Miller
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Article |
Inflammasome-mediated dysbiosis regulates progression of NAFLD and obesity
An expansion of Porphyromonadaceae in the gut is linked to the pathogenesis and progression of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis in the mouse.
- Jorge Henao-Mejia
- , Eran Elinav
- & Richard A. Flavell
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