Gastroenterology articles within Nature Communications

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  • Article
    | Open Access

    BTLA is established as a negative regulator of natural killer T (NKT) cell function, and share its ligand HVEM with CD160. Here the authors show, by analyzing NKT activation in CD160-deficient mice or with BTLA blockade, that CD160 synergizes with BTLA to negatively regulate NKT cells during hepatic injury.

    • Tae-Jin Kim
    • , Gayoung Park
    •  & Kyung-Mi Lee

  • Article
    | Open Access

    The roles played by thrombin in the human intestinal mucosa are unclear. Here, the authors show that the commensal microbiota modulates epithelial production of active thrombin, which controls biofilm growth and contributes to protection of the mucosa from bacterial invasion.

    • Jean-Paul Motta
    • , Alexandre Denadai-Souza
    •  & Nathalie Vergnolle

  • Article
    | Open Access

    Alcoholic hepatitis, a common cause of liver failure, lacks effective treatment. Here, the authors show altered hepatic HNF4a isoform expression and hypermethylation of its target genes in patients. HNF4a dysregulation is improved in vitro by TGFb or PPARg modulation suggesting potential therapeutic avenues.

    • Josepmaria Argemi
    • , Maria U. Latasa
    •  & Ramon Bataller

  • Article
    | Open Access

    Trefoil factor 1 (TFF1) is a protein secreted by the gastric mucosa that protects against gastric tumourigenesis. Here, the authors show that TFF1 inhibits the oncogenic inflammatory response and IL-6-mediated STAT3 activation by interfering with the binding of IL6 to its receptor IL6Rα.

    • Mohammed Soutto
    • , Zheng Chen
    •  & Wael El-Rifai

  • Article
    | Open Access

    Clinical and molecular heterogeneity of ulcerative colitis presents unresolved challenges to identify predictive biomarkers of response to therapies. Here, the authors combine mouse colitis time course with patient biopsy transcriptomes, achieving unsupervised clustering of UC patients correlating with therapeutic outcomes in independent data sets.

    • Paulo Czarnewski
    • , Sara M. Parigi
    •  & Eduardo J. Villablanca

  • Article
    | Open Access

    Hyperspectral imaging (HSI) enables recording both morphological and biochemical information, but image acquisition time and geometric distortions limit its clinical applicability. Here the authors overcome these challenges with an endoscope combining HSI and white light to correct for image distortion during freehand operation.

    • Jonghee Yoon
    • , James Joseph
    •  & Sarah E. Bohndiek

  • Article
    | Open Access

    The histone variant, H2A.Z is known to regulate gene expression and cell proliferation. Here the authors show that H2A.Z has a central role in the control of intestinal epithelial homeostasis in mice, by preventing terminal differentiation of intestinal progenitors.

    • Jérémie Rispal
    • , Lucie Baron
    •  & Fabrice Escaffit

  • Article
    | Open Access

    Early life stress has been associated with the occurrence of gastrointestinal diseases later in life, but underlying mechanisms remain poorly understood. Here, Wong et al. show that early life stress leads to expansion of intestinal stem cells and their differentiation into serotonin-producing enterochromaffin cells through crosstalk between NGF and Wnt signalling pathways.

    • Hoi Leong Xavier Wong
    • , Hong-yan Qin
    •  & Zhao-xiang Bian

  • Article
    | Open Access

    Development of cirrhosis in individuals with non-alcoholic fatty liver disease can predict mortality. Here the authors used a unique twin and family cohort to identify a gut microbiome-derived 16sRNA signature that can detect cirrhosis in individuals with non-alcoholic fatty liver disease.

    • Cyrielle Caussy
    • , Anupriya Tripathi
    •  & Rohit Loomba

  • Article
    | Open Access

    Gluten triggers celiac disease in genetically predisposed individuals, but additional unknown mechanisms are required. Here, the authors show that proteases from Pseudomonas aeruginosa can modulate inflammatory pathways that are relevant to the development of food sensitivities, independently of the trigger antigen.

    • Alberto Caminero
    • , Justin L. McCarville
    •  & Elena F. Verdu

  • Article
    | Open Access

    Innate lymphoid cells (ILC), including natural killer (NK) cells, are important innate immune regulators. Here the authors show that, in human infant intestines, CD103+Eomes+ NK cells are the predominant ILC population, but are replaced gradually by Eomes+ T cells, while NKp44+ NK cells persist in adult intestines.

    • Adrian F. Sagebiel
    • , Fenja Steinert
    •  & Madeleine J. Bunders

  • Article
    | Open Access

    Endoplasmic reticulum (ER) stress has been proposed to play a role in metabolic diseases. Here, Sasako and colleagues identify stromal cell-derived factor 2 like 1 (Sdf2l1) as a regulator of the ER stress response to feeding in the liver, and suggest that its downregulation may promote diabetes and hepatic steatosis in humans.

    • Takayoshi Sasako
    • , Mitsuru Ohsugi
    •  & Kohjiro Ueki

  • Article
    | Open Access

    Urolithins are microbial metabolites derived from food polyphenols. Here, Singh et al. show that urolithin A and a synthetic analogue enhance gut barrier function via Nrf2-dependent pathways and mitigate inflammation and colitis in mice, highlighting a potential application for inflammatory bowel diseases.

    • Rajbir Singh
    • , Sandeep Chandrashekharappa
    •  & Venkatakrishna R. Jala

  • Article
    | Open Access

    Tr1 cells are considered an immunosuppressive CD4 T cell population producing IL-10. Here the authors show that IL-10 is insufficient for Tr1 immunosuppression, define surface markers and transcriptional program of the immunosuppressive subset within Tr1, and reveal its deficiency in patients with IBD.

    • Leonie Brockmann
    • , Shiwa Soukou
    •  & Samuel Huber

  • Article
    | Open Access

    Cubilin and the transmembrane protein amnionless (AMN) form the endocytic receptor cubam that is essential for intestinal vitamin B12 uptake. Here the authors present the 2.3 Å crystal structure of AMN in complex with the amino-terminal region of cubilin and discuss cubam architecture and disease causing mutations.

    • Casper Larsen
    • , Anders Etzerodt
    •  & Christian Brix Folsted Andersen

  • Article
    | Open Access

    Obesity increases the risk of hepatocellular carcinoma (HCC) especially in men. Here the authors find a potential mechanistic explanation by showing that, in mice, obesity-induced STAT3 cooperates with the androgen receptor to activate the mTORC pathway through up regulation of CCRK, resulting in hepatic steatosis worsening and HCC development via metabolic and immune reprogramming.

    • Hanyong Sun
    • , Weiqin Yang
    •  & Alfred S. L. Cheng

  • Article
    | Open Access

    Faecal microbiota transplantation (FMT) is becoming a therapeutic option in several gastrointestinal disorders. Here, Burrello et al. study the immunological mechanisms by which FMT reduces colonic inflammation and initiates the restoration of intestinal homeostasis in a mouse model of colitis.

    • Claudia Burrello
    • , Federica Garavaglia
    •  & Federica Facciotti

  • Article
    | Open Access

    Genome-wide association studies have so far identified eight risk loci for gallstone disease. Here, the authors perform meta-analysis in cohorts from Iceland and the UK which reveals further 21 common and low-frequency risk variants that highlight the role of bile acid homeostasis in gallstone disease.

    • Egil Ferkingstad
    • , Asmundur Oddsson
    •  & Kari Stefansson

  • Article
    | Open Access

    SLIT-ROBO alterations arise in pancreatic ductal adenocarcinoma (PDAC), but their role in the pancreas is unclear. Here, the authors use mouse models to show that loss of epithelial Robo2 activates the neighbouring stroma via TGF-β signalling; findings  are relevant to PDAC patients, where ROBO expression correlates with survival outcomes.

    • Andreia V. Pinho
    • , Mathias Van Bulck
    •  & Ilse Rooman

  • Article
    | Open Access

    Inflammatory diseases of the pancreas are currently untreatable and lack a pre-clinical model that recapitulates the hallmarks of the human pathology. Here, the authors generate a knock-in mouse strain with increased tripsinogen autoactivation and show that it develops spontaneous pancreatic pathology with some key features of human pancreatitis.

    • Andrea Geisz
    •  & Miklós Sahin-Tóth

  • Article
    | Open Access

    Neonatal rotavirus infections are associated with gastrointestinal symptoms in some settings, but the role of host factors in clinical presentation is unclear. Here, Ramani et al. show that human milk oligosaccharides and microbiome are associated with symptomatic infection with neonatal strain G10P[11].

    • Sasirekha Ramani
    • , Christopher J. Stewart
    •  & Mary K. Estes

  • Article
    | Open Access

    No effective pharmacological treatments exist for nonalcoholic fatty liver disease (NAFLD). Here, the authors show that serotonin concentration in the portal blood is increased in nine human subjects and in mice fed a high-fat diet, and that local serotonin signaling ablation, either genetically or with an antagonist, prevents hepatic steatosis in mice.

    • Wonsuk Choi
    • , Jun Namkung
    •  & Hail Kim

  • Article
    | Open Access

    CD8 T cells can protect the liver from viral infection, but can also result in severe liver damage and organ failure. Here, the authors develop a mouse model reflecting fulminant CD8 T cell mediated viral hepatitis, which occurs in a perforin-dependent manner that is protected by the use of perforin inhibitors.

    • M. Welz
    • , S. Eickhoff
    •  & W. Kastenmüller

  • Article
    | Open Access

    Gluten-free diets are increasingly common in the general population. Here, the authors report the results of a randomised cross-over trial involving middle-aged, healthy Danish adults, showing evidence that a low-gluten diet leads to gut microbiome changes, possibly due to variations in dietary fibres.

    • Lea B. S. Hansen
    • , Henrik M. Roager
    •  & Oluf Pedersen

  • Article
    | Open Access

    The development of single cell RNA sequencing technologies has been instrumental in advancing our understanding of tissue biology. Here, MacParland et al. performed single cell RNA sequencing of human liver samples, and identify distinct populations of intrahepatic macrophages that may play specific roles in liver disease.

    • Sonya A. MacParland
    • , Jeff C. Liu
    •  & Ian D. McGilvray

  • Article
    | Open Access

    Inflammatory bowel disease is characterised by epithelial dysfunction. Here the authors show that loss of the nuclear receptor LRH-1 leads to epithelial disruption by altering Notch signaling in mouse intestinal organoids, and that LRH-1 overexpression ameliorates immune-mediated colitis in a mouse model.

    • James R. Bayrer
    • , Hongtao Wang
    •  & Holly A. Ingraham

  • Article
    | Open Access

    Studies on the effects of breastfeeding on the infant gut microbiota have provided inconsistent results. Here, Ho et al. perform a meta-analysis of seven studies across different populations, supporting that exclusive breastfeeding is associated with short-term and long-term alterations in the infant gut microbiota.

    • Nhan T. Ho
    • , Fan Li
    •  & Louise Kuhn

  • Article
    | Open Access

    Spatial mapping of genomic programs in tissue cells is an important step in the understanding of organ function and disease. Here, the authors provide a spatially resolved epigenomic and transcriptomic map of human liver and show porto-central gradients in metabolic and morphogen networks and transcription factor binding sites as a basis to better understand liver regeneration and function.

    • Mario Brosch
    • , Kathrin Kattler
    •  & Jochen Hampe

  • Article
    | Open Access

    Fecal microbiota transplantation (FMT) is effective in treating recurrent Clostridium difficile infection (CDI). Here, the authors show that the composition of the gut fungal microbiota of donors and recipients, and especially the abundance of Candida, correlates with FMT outcome in CDI patients.

    • Tao Zuo
    • , Sunny H. Wong
    •  & Siew C. Ng

  • Review Article
    | Open Access

    Gut microbial metabolites are known to impact many physiological processes of the host and play a critical role in immune-homeostasis. Here the authors review our current understanding and appreciation of the importance of microbially derived tryptophan catabolites during both health and disease.

    • Henrik M. Roager
    •  & Tine R. Licht

  • Article
    | Open Access

    In intestinal adenomas carrying active β-catenin, Jagged1 (Jag1) ligand is responsible for Notch1 activation. Here, the authors show the reliance of Notch on Jag1 in cancer, and investigate how Jag1–Notch1 signaling interference may provide therapeutic benefits in some colorectal cancer patients

    • Erika López-Arribillaga
    • , Verónica Rodilla
    •  & LLuís Espinosa

  • Article
    | Open Access

    The LXR-SREBP1c pathway promotes hepatic lipogenesis that is deregualted in fatty liver disease. Here the authors show that the long noncoding RNA Blnc1 contributes to the development of obesity-driven steatosis by enabling SREBP1c trascriptional activity in response to LXR activation.

    • Xu-Yun Zhao
    • , Xuelian Xiong
    •  & Jiandie D. Lin

  • Article
    | Open Access

    Gut microbial dysbiosis has been implicated in the pathogenesis of inflammatory bowel disease. Here, the authors examine host-microbiota protein interactions that occur in inflammatory bowel disease; they show an upregulation in proteins related to antimicrobial activities, and alterations in intestinal extracellular vesicles that are associated with aberrant microbiota-interactions.

    • Xu Zhang
    • , Shelley A. Deeke
    •  & Daniel Figeys

  • Article
    | Open Access

    Insulin promotes lipogenesis but, on the other hand, insulin resistance is associated with increased lipogenesis in the liver. Here the authors show that Snail1 is upregulated by insulin and inhibits lipogenesis by repressing Fasn expression but insulin-mediated Snail1 upregulation is impaired during obesity and insulin resistance.

    • Yan Liu
    • , Lin Jiang
    •  & Liangyou Rui

  • Article
    | Open Access

    FXR plays an important role in bile acid homeostasis by transcriptionally modulating several enterohepatic genes, including intestinal FGF19, that repress hepatic bile acid synthesis. Here the authors show that postprandial FGF19 regulates FXR transcriptional activity via its action on the tyrosine kinase Src, which phosphorylates FXR.

    • Sangwon Byun
    • , Dong-Hyun Kim
    •  & Jongsook Kim Kemper

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