Gastrointestinal system

  • Article
    | Open Access

    Transition zones connect distinct epithelia, contain cells expressing stem cell markers, and contribute to cancer development. Here, the authors examine the mouse anorectal junction, identifying a population of Krt17-positive basal cells that contribute to squamous and glandular epithelia during homeostasis and repair.

    • Louciné Mitoyan
    • , Véronique Chevrier
    •  & Géraldine Guasch
  • Article
    | Open Access

    Gut microbiome alterations have been linked to inflammatory bowel disease (IBD) and obesity. Here, the authors characterize the metagenomes of four large human cohorts and perform co-abundance network analysis showing that dysbiosis in disease is marked by the altered co-abundance relationships, suggesting that pathway coabundance networks are more heterogeneous than species network.

    • Lianmin Chen
    • , Valerie Collij
    •  & Jingyuan Fu
  • Article
    | Open Access

    The common ABCG2 variant Q141K contributes to hyperuricemia and gout risk. Here, using a human interventional study and a new orthologous mouse model, the authors report a tissue specific pathobiology of the Q141K variant, and support a significant role for ABCG2 in urate excretion in both the kidney and intestine.

    • Kazi Mirajul Hoque
    • , Eryn E. Dixon
    •  & Owen M. Woodward
  • Article
    | Open Access

    Deriving functional pancreatic cell types from human stem cells may have important clinical applications. Building on previous work, here the authors generate stem cell-derived alpha cells via a polyhormonal intermediate, which have a gene expression pattern similar to human islet alpha cells and behave as such when transplanted into mice.

    • Quinn P. Peterson
    • , Adrian Veres
    •  & Douglas A. Melton
  • Article
    | Open Access

    Glucose metabolism is regulated by hypothalamic brain functions and factors produced by peripheral tissues. Here, the authors show that the regulator of food intake Brain-derived neurotrophic factor is also produced and secreted by muscle and stimulates pancreas insulin release.

    • Gianluca Fulgenzi
    • , Zhenyi Hong
    •  & Lino Tessarollo
  • Article
    | Open Access

    Intestinal aging is associated with declines in structure and absorption of nutrients. Here, the authors show that aging related intestinal decline is mediated by activation of the mTORC1-p38MAPK-p53 pathway in intestinal stem cells and can be ameliorated by abrogating mTORC1 or p38MAPK activity.

    • Dan He
    • , Hongguang Wu
    •  & Baojie Li
  • Article
    | Open Access

    Histone deacetylase 3 (HDAC3) is a regulator of lipid homeostasis in several tissues, however, its role in intestinal lipid metabolism was not yet known. Here the authors study intestine specific HDAC3 knock out mice and report that these animals have increased fatty acid oxidation and undergo remodeling of the intestinal epithelial cell lipidome.

    • Mercedes Dávalos-Salas
    • , Magdalene K. Montgomery
    •  & John M. Mariadason
  • Article
    | Open Access

    In a large prospective cohort of liver transplantation (LT) recipients, the authors identify associations between colonization by multidrug-resistant bacteria (MDRB) and microbiome dysbiosis pre- and post-LT, suggesting colonizing MDRB as an important target for microbiome-informed therapeutic approaches post-LT.

    • Medini K. Annavajhala
    • , Angela Gomez-Simmonds
    •  & Anne-Catrin Uhlemann
  • Article
    | Open Access

    Necrotizing enterocolitis (NEC) is associated with severe neonatal morbidity. Here the authors show, mirroring the NEC phenotype, that IL-23 overexpression in neonates causes malabsorption and decreased expression of intestinal and pancreatic genes mediating food digestion and uptake through IL-22, which directly suppresses pancreatic cell differentiation.

    • Lili Chen
    • , Valentina Strohmeier
    •  & Glaucia C. Furtado
  • 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

    Berberine has lipid-lowering effects and other metabolic benefits, but it presents with poor bioavailability. Here the authors conjugate berberine to liver-targeting nanoparticles, and show increased accumulation of berberine in the liver, improved metabolic profiles and reduced atherosclerotic plaques in mice.

    • Hui-Hui Guo
    • , Chen-Lin Feng
    •  & Jian-Dong Jiang
  • 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

    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

    The human stomach is divided into seven anatomically distinct regions but their protein composition is largely unknown. Here, the authors present a region-resolved map of the healthy human stomach mucosa as well as mucosa proteomes of tumor and tumor nearby tissue from gastric cancer patients.

    • Xiaotian Ni
    • , Zhaoli Tan
    •  & Jun Qin
  • 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 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

    Coordinated proliferation and differentiation of diverse cell populations drive pancreatic epithelial and mesenchymal development. Here, the authors profile cell type dynamics in the developing mouse pancreas using single-cell RNA sequencing, identifying mesenchymal subtypes and undescribed endocrine progenitors.

    • Lauren E. Byrnes
    • , Daniel M. Wong
    •  & Julie B. Sneddon
  • Article
    | Open Access

    The role of the gut microbiota in hepatic lipid metabolism is controversial and incompletely understood. Here the authors perform multi-omics analyses of altered lipid metabolic processes in germ-free and specific pathogen-free mice, revealing how the gut microbiota affects hepatic fatty acid desaturation and elongation.

    • Alida Kindt
    • , Gerhard Liebisch
    •  & Josef Ecker
  • 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

    Gut microbial dysbiosis in infancy is associated with childhood atopy and the development of asthma. Here, the authors show that gut microbiota perturbation is evident in the very earliest stages of postnatal life, continues throughout infancy, and can be partially rescued by Lactobacillus supplementation in high-risk for asthma infants.

    • Juliana Durack
    • , Nikole E. Kimes
    •  & Susan V. Lynch
  • Article
    | Open Access

    Short-chain fatty acids (SCFA) are a main class of metabolites derived from fermentation of dietary fibre in the intestine. Here, the authors show that dietary administration of SCFA is associated with inhibition of osteoclast differentiation, increased bone mass, and reduced pathological bone loss in mice.

    • Sébastien Lucas
    • , Yasunori Omata
    •  & Mario M. Zaiss
  • Article
    | Open Access

    There is a need for humanised grafts to treat patients with intestinal failure. Here, the authors generate intestinal grafts by recellularizing native intestinal matrix with human induced pluripotent stem cell-derived epithelium and human endothelium, and show nutrient absorption after transplantation in rats.

    • Kentaro Kitano
    • , Dana M. Schwartz
    •  & Harald C. Ott
  • Article
    | Open Access

    Βeta-cells have recently been shown to be heterogeneous with regard to morphology and function. Here, the authors show that β-cells in zebrafish switch from proliferative to functional states with increasing time since β-cell birth, leading to functional and proliferative heterogeneity.

    • Sumeet Pal Singh
    • , Sharan Janjuha
    •  & Nikolay Ninov
  • Article
    | Open Access

    Human liver chimeric mice are increasingly used for drug testing in preclinical development, but express residual murine p450 cytochromes. Here the authors generate mice lacking the Por gene in the liver, and show that human cytochrome metabolism is used following repopulation with human hepatocytes.

    • Mercedes Barzi
    • , Francis P. Pankowicz
    •  & Karl-Dimiter Bissig
  • Article
    | Open Access

    M cells are intestinal epithelial cells that are specialized to transcytose antigens and bacteria from the intestinal lumen to antigen presenting cells on the other side. Here the authors show that the actin-binding protein Aif1 is highly expressed by intestinal M cells and regulates this transcytosis.

    • Sari Kishikawa
    • , Shintaro Sato
    •  & Hiroshi Kiyono
  • Article
    | Open Access

    Mice deficient in the pro-inflammatory cytokine IFNγ have improved glucose tolerance. Here, the authors show that this effect depends on the gut microbeAkkermansia muciniphila, whose abundance increases in the absence IFNγ, and which is known to have beneficial effects on host metabolism.

    • Renee L. Greer
    • , Xiaoxi Dong
    •  & Natalia Shulzhenko
  • Article
    | Open Access

    Diabetes is associated with the de-differentiation of β-cells into a more progenitor-like cell type. Here, the authors identify Aldh3 as a marker of de-differentiating β-cell in animal models of diabetes, and show Aldh3+cells have impaired insulin secretion and mitochondrial dysfunction.

    • Ja Young Kim-Muller
    • , Jason Fan
    •  & Domenico Accili
  • Article
    | Open Access

    The accessory olfactory system (AOS) processes social chemosensory information and guides behaviors that are important for survival and reproduction in mammals. Here the authors report that mouse feces are a source of AOS neuronal activity and identify unconjugated bile acids in feces as a class of natural AOS ligands.

    • Wayne I. Doyle
    • , Jordan A. Dinser
    •  & Julian P. Meeks
  • Article
    | Open Access

    The interactions between gut bacteria and enteric pathogens are poorly understood. Here, Yoon et al. show that subinhibitory antibiotic treatment in a mouse model leads to overgrowth of an E. coli strain carrying a catalase-encoding gene that enhances infection with the human pathogen Vibrio cholerae.

    • Mi Young Yoon
    • , Kyung Bae Min
    •  & Sang Sun Yoon
  • Article
    | Open Access

    The molecular basis of the basal tone generated by internal anal sphincters (IAS) is largely unknown. Here, the authors show that the tone arises from a global rise in intracellular Ca2+ in smooth muscle cells via a Ryanodine receptor-TMEM16A-L-type Ca2+channel-MLC kinase pathway, suggesting a potential therapy for IAS motility disorders.

    • Cheng-Hai Zhang
    • , Pei Wang
    •  & Min-Sheng Zhu
  • Article
    | Open Access

    Commensal microbes are necessary for proper development of the immune system. Here Zanvit et al. show that neonatal antibiotics treatment causes long-term changes in the gut and skin microbiomes, and exacerbates immune-mediated skin pathology at adult age in mouse experimental models of psoriasis.

    • Peter Zanvit
    • , Joanne E. Konkel
    •  & WanJun Chen
  • Article
    | Open Access

    The inner layer of the mucus that covers our intestine is nearly sterile. Here, the authors show in mice that the outer mucus layer constitutes a unique microbial niche hosting bacterial communities with distinct proliferation rates and resource utilization activities.

    • Hai Li
    • , Julien P. Limenitakis
    •  & Andrew J. Macpherson
  • Article
    | Open Access

    The potential recovery of the human gut microbiota after an antibiotic treatment, and its effects on our health, are poorly understood. Here, the authors use a mouse model mimicking paediatric antibiotic use to shed new light into these processes.

    • Yael R. Nobel
    • , Laura M. Cox
    •  & Martin J. Blaser
  • Article
    | Open Access

    The human gut microbiota helps us to degrade complex dietary carbohydrates such as xylan and, in turn, the carbohydrate breakdown products control the structure of the microbiota. Here the authors characterize the xylan-degrading apparatus of a key member of the gut microbiota, Bacteroides ovatus.

    • Artur Rogowski
    • , Jonathon A. Briggs
    •  & David N. Bolam
  • Article
    | Open Access

    Ganoderma lucidumis a medicinal mushroom used in Traditional Chinese Medicine with putative anti-diabetic properties. Here, the authors show that polysaccharides from a water extract of this mushroom exert beneficial metabolic effects by modulating the composition of the gut microbiota in mice.

    • Chih-Jung Chang
    • , Chuan-Sheng Lin
    •  & Hsin-Chih Lai
  • Article
    | Open Access

    Bile acids are important for the absorption of nutrients. Here the authors provide a molecular explanation for the oscillatory release of bile acids, showing that diurnal expression of the transcription factor KLF15 regulates FGF15 secretion from enterocytes, which then inhibits bile acid synthesis in the liver.

    • Shuxin Han
    • , Rongli Zhang
    •  & Mukesh K. Jain