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Mutations of the NOD2 gene are risk factors for Crohn’s disease. Many aspects of how they contribute to the condition are unknown. The discovery of cell populations that are involved suggests new therapeutic options. Cell populations shed light on how NOD2 mutations contribute to disease.

Some studies suggest that the community of microorganisms that live in the gut are associated with athleticism. Some studies suggest that the community of microorganisms that live in the gut are associated with athleticism.

Debilitating gut pain is common, but the underlying cause is often unclear. It emerges that gut infection triggers localized immune responses that cause normally innocuous foods to be perceived as harmful, leading to persistent pain. Defence against bacterial infection can drive pain when eating food.

Inflammatory bowel diseases, which include Crohn’s disease and ulcerative colitis, affect several million individuals worldwide. Crohn’s disease and ulcerative colitis are complex diseases that are heterogeneous at the clinical, immunological, molecular, genetic, and microbial levels. Individual contributing factors have been the focus of extensive research. As part of the Integrative Human Microbiome Project (HMP2 or iHMP), we followed 132 subjects for one year each to generate integrated longitudinal molecular profiles of host and microbial activity during disease (up to 24 time points each; in total 2,965 stool, biopsy, and blood specimens). Here we present the results, which provide a comprehensive view of functional dysbiosis in the gut microbiome during inflammatory bowel disease activity. We demonstrate a characteristic increase in facultative anaerobes at the expense of obligate anaerobes, as well as molecular disruptions in microbial transcription (for example, among clostridia), metabolite pools (acylcarnitines, bile acids, and short-chain fatty acids), and levels of antibodies in host serum. Periods of disease activity were also marked by increases in temporal variability, with characteristic taxonomic, functional, and biochemical shifts. Finally, integrative analysis identified microbial, biochemical, and host factors central to this dysregulation. The study’s infrastructure resources, results, and data, which are available through the Inflammatory Bowel Disease Multi’omics Database (http://ibdmdb.org), provide the most comprehensive description to date of host and microbial activities 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.

The World Health Organization is sending scientists to China this weekend to investigate the origins of the COVID-19 outbreak. The World Health Organization is sending scientists to China this weekend to investigate the origins of the COVID-19 outbreak.

Abandoned experiments have to be restarted — sometimes from scratch. Abandoned experiments have to be restarted — sometimes from scratch.

Up to 20% of people worldwide develop gastrointestinal symptoms following a meal(1), leading to decreased quality of life, substantial morbidity and high medical costs. Although the interest of both the scientific and lay communities in this issue has increased markedly in recent years, with the worldwide introduction of gluten-free and other diets, the underlying mechanisms of food-induced abdominal complaints remain largely unknown. Here we show that a bacterial infection and bacterial toxins can trigger an immune response that leads to the production of dietary-antigen-specific IgE antibodies in mice, which are limited to the intestine. Following subsequent oral ingestion of the respective dietary antigen, an IgE- and mast-cell-dependent mechanism induced increased visceral pain. This aberrant pain signalling resulted from histamine receptor H-1-mediated sensitization of visceral afferents. Moreover, injection of food antigens (gluten, wheat, soy and milk) into the rectosigmoid mucosa of patients with irritable bowel syndrome induced local oedema and mast cell activation. Our results identify and characterize a peripheral mechanism that underlies food-induced abdominal pain, thereby creating new possibilities for the treatment of irritable bowel syndrome and related abdominal pain disorders. 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.

Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia Use techniques honed during the SARS, H1N1 and Ebola epidemics to separate sick and well, keep workers safe and prepare for the next outbreak, says Nahid Bhadelia

Studies have pointed to a link between colon cancer and a gut bacterium that produces DNA-damaging molecules. The discovery of a mutational signature linked to these bacteria in human colon cancer supports this association. Specific DNA alterations in human cancer might be due to a gut microbe.

Transplants of faecal matter have done wonders for the treatment of certain gastrointestinal infections. Will they ever work for inflammatory bowel disease?

The digitisation of medical records in the United States has brought benefits, but not everyone is content with how they have been implemented. The digitisation of medical records in the United States has brought benefits, but not everyone is content with how they have been implemented.

Many long-term diseases of the liver lead to scarring, or fibrosis, that restricts the organ’s functions. Evidence that fibrosis can regress has spurred the search for therapies that suppress scar-tissue formation to restore liver health. Many long-term diseases of the liver lead to scarring, or fibrosis, that restricts the organ’s functions. Evidence that fibrosis can regress has spurred the search for therapies that suppress scar-tissue formation to restore liver health.

The public’s view of artificial intelligence may not be accurate, but that doesn’t mean that those developing new technologies can afford to ignore it. The public’s view of artificial intelligence may not be accurate, but that doesn’t mean that those developing new technologies can afford to ignore it.

Harvey Alter, Michael Houghton and Charles Rice share the award for research on a virus that causes hundreds of thousands of deaths a year. Harvey Alter, Michael Houghton and Charles Rice share the award for research on a virus that causes hundreds of thousands of deaths a year.

Inflammatory bowel disease is a growing problem in Asia. But that increase presents a golden opportunity for research.

Cells compete for survival during development. It emerges that mammalian cells on a path to form a tumour express specific versions of the protein Flower when they vie for survival with surrounding normal cells. Which version of a protein called Flower that is made affects cell survival.

Biotechnology start-ups and pharmaceutical giants alike are charging ahead to develop therapies for the most serious form of non-alcoholic fatty liver disease. Biotechnology start-ups and pharmaceutical giants alike are charging ahead to develop therapies for the most serious form of non-alcoholic fatty liver disease

Since its discovery in 1989, efforts to grow clinical isolates of the hepatitis C virus (HCV) in cell culture have met with limited success. Only the JFH-1 isolate has the capacity to replicate efficiently in cultured hepatoma cells without cell culture-adaptive mutations. We hypothesized that cultured cells lack one or more factors required for the replication of clinical isolates. To identify the missing factors, we transduced Huh-7.5 human hepatoma cells with a pooled lentivirus-based human complementary DNA (cDNA) library, transfected the cells with HCV subgenomic replicons lacking adaptive mutations, and selected for stable replicon colonies. This led to the identification of a single cDNA, SEC14L2, that enabled RNA replication of diverse HCV genotypes in several hepatoma cell lines. This effect was dose-dependent, and required the continuous presence of SEC14L2. Full-length HCV genomes also replicated and produced low levels of infectious virus. Remarkably, SEC14L2-expressing Huh-7.5 cells also supported HCV replication following inoculation with patient sera. Mechanistic studies suggest that SEC14L2 promotes HCV infection by enhancing vitamin E-mediated protection against lipid peroxidation. This provides a foundation for development of in vitro replication systems for all HCV isolates, creating a useful platform to dissect the mechanisms by which cell culture-adaptive mutations act.

Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality. ispartof: NATURE vol:557 issue:7703 pages:50-+ ispartof: location:England status: published

Liver cirrhosis occurs as a consequence of many chronic liver diseases that are prevalent worldwide. Here we characterize the gut microbiome in liver cirrhosis by comparing 98 patients and 83 healthy control individuals. We build a reference gene set for the cohort containing 2.69 million genes, 36.1% of which are novel. Quantitative metagenomics reveals 75,245 genes that differ in abundance between the patients and healthy individuals (false discovery rate

People waiting for a liver transplant can die before an organ is found, or, if one is available but of poor quality, there is a risk of transplant failure. A machine that preserves livers might offer a way forward. People waiting for a liver transplant can die before an organ is found, or, if one is available but of poor quality, there is a risk of transplant failure. A machine that preserves livers might offer a way forward.

Modifying the population of bacteria in the gut might help to prevent and treat non-alcoholic fatty liver disease. Modifying the population of bacteria in the gut might help to prevent and treat non-alcoholic fatty liver disease.

Once thought to be irreversible, cirrhosis of the liver now seems treatable — and drug development is proceeding apace. Once thought to be irreversible, cirrhosis of the liver now seems treatable — and drug development is proceeding apace.

In this Article, the pCaMIN construct consisted of ‘mouse MYC and mouse NrasG12V’ instead of ‘mouse Myc and human NRASG12V; and the pCAMIA construct consisted of ‘mouse Myc and human AKT1’ instead of ‘mouse Myc and Akt1’ this has been corrected online.

Hepatocytes are replenished gradually during homeostasis and robustly after liver injury1, 2. In adults, new hepatocytes originate from the existing hepatocyte pool3-8, but the cellular source of renewing hepatocytes remains unclear. Telomerase is expressed in many stem cell populations, and mutations in telomerase pathway genes have been linked to liver diseases9-11. Here we identify a subset of hepatocytes that expresses high levels of telomerase and show that this hepatocyte subset repopulates the liver during homeostasis and injury. Using lineage tracing from the telomerase reverse transcriptase (Tert) locus in mice, we demonstrate that rare hepatocytes with high telomerase expression (TERTHigh hepatocytes) are distributed throughout the liver lobule. During homeostasis, these cells regenerate hepatocytes in all lobular zones, and both self-renew and differentiate to yield expanding hepatocyte clones that eventually dominate the liver. In response to injury, the repopulating activity of TERTHigh hepatocytes is accelerated and their progeny cross zonal boundaries. RNA sequencing shows that metabolic genes are downregulated in TERTHigh hepatocytes, indicating that metabolic activity and repopulating activity may be segregated within the hepatocyte lineage. Genetic ablation of TERTHigh hepatocytes combined with chemical injury causes a marked increase in stellate cell activation and fibrosis. These results provide support for a 'distributed model' of hepatocyte renewal in which a subset of hepatocytes dispersed throughout the lobule clonally expands to maintain liver mass.

There is a long list of unknowns about the causes and symptomatology of irritable bowel syndrome (IBS). But the research challenges can be distilled into four key areas.

The latest iteration of the Rome criteria should improve diagnosis of irritable bowel syndrome, says Brian E. Lacy.

Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and the leading cause of chronic liver disease in the Western world. Twenty per cent of NAFLD individuals develop chronic hepatic inflammation (non-alcoholic steatohepatitis, NASH) associated with cirrhosis, portal hypertension and hepatocellular carcinoma, yet the causes of progression from NAFLD to NASH remain obscure. Here, we show that the NLRP6 and NLRP3 inflammasomes and the effector protein IL-18 negatively regulate NAFLD/NASH progression, as well as multiple aspects of metabolic syndrome via modulation of the gut microbiota. Different mouse models reveal that inflammasome-deficiency-associated changes in the configuration of the gut microbiota are associated with exacerbated hepatic steatosis and inflammation through influx of TLR4 and TLR9 agonists into the portal circulation, leading to enhanced hepatic tumour-necrosis factor (TNF)-α expression that drives NASH progression. Furthermore, co-housing of inflammasome-deficient mice with wild-type mice results in exacerbation of hepatic steatosis and obesity. Thus, altered interactions between the gut microbiota and the host, produced by defective NLRP3 and NLRP6 inflammasome sensing, may govern the rate of progression of multiple metabolic syndrome-associated abnormalities, highlighting the central role of the microbiota in the pathogenesis of heretofore seemingly unrelated systemic auto-inflammatory and metabolic disorders. 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. Using a mouse model, Richard Flavell and co-workers study the inflammatory processes associated with progression from non-alcoholic fatty liver disease — the leading cause of chronic liver disease in developed countries — to the more severe non-alcoholic steatohepatitis, which often leads to cirrhosis and hepatocellular carcinoma. They find that alterations of the intestinal microbiota associated with the NLRP6 and NLRP3 inflammasomes enhance disease in mice with diet-induced non-alcoholic fatty liver syndrome. These findings highlight the pivotal role of the microbiota in the development of autoinflammatory and metabolic disorders, and point to the manipulation of host–microflora interactions as a focus for new therapies.

A protocol has been developed to grow structures that resemble the main part of the stomach in vitro from human embryonic stem cells — an advance that provides insights into stomach development. See Article p.182 Using a mouse model for stomach development, James Wells and colleagues have delineated the requirement of Wnt signalling for specification of the fundus region of the stomach in mammals—the upper part of the stomach close to the cardial notch and oesophagus. On the basis of this finding, the authors develop human gastric organoids derived from fundic pluripotent stem cells, which should provide a powerful model for the study of gastric physiology and pathophysiology, as well as for drug discovery.

Gene exploration is providing unexpected insights into inflammatory bowel disease, and getting scientists closer to finding treatments that target the biological mechanisms.

Nature 547, 350–354 (2017); doi:10.1038/nature23015 In Extended Data Fig. 10b of this Letter, the axes of the single-cell gating (middle panel) FACS plots were mislabelled. Single cells were gated using forward scatter area (FSC-A) against height (FSC-H) on a linear scale, instead of side scatter area (SSC-A) against height (SSC-H) on a log scale.

A progressive and potentially life-threatening condition previously associated with alcoholism is becoming more common — even in non-drinkers.

Hepatitis C virus (HCV) infection is the most common blood borne infection in the U.S. with estimates of 4 million HCV-infected individuals in the U.S. and 170 million worldwide1. The majority (70%–80%) of HCV infections persist and about 30% of individuals with persistent infection develop chronic liver disease, including cirrhosis and hepatocellular carcinoma2. Epidemiological, viral, and host factors have been associated with the differences in HCV clearance or persistence and studies have demonstrated that a strong host immune response against HCV favors viral clearance3,4. Thus, variation in genes involved in the immune response may contribute to the ability to clear the virus. In a recent genome-wide association study, a single nucleotide polymorphism (rs12979860) 3kb upstream of the IL28B gene, which encodes the type III interferon IFN-λ3, was shown to associate strongly with more than a 2-fold difference in response to HCV drug treatment5. To determine the potential effect of rs12979860 variation on outcome to HCV infection in a natural history setting, we genotyped this variant in HCV cohorts comprised of individuals who spontaneously cleared the virus (N = 388) or had persistent infection (N = 620). We show that the C/C genotype strongly enhances resolution of HCV infection amongst individuals of both European and African ancestry (European: OR = 0.38, p = 10−7; African: OR = 0.32, p = 10−4; combined: OR = 0.33, p

Many people with irritable bowel syndrome feel that they benefit from dietary interventions, but researchers still lack a full understanding of how food can inflame this disorder.

Peter Whorwell is Director of the South Manchester Neurogastroenterology Service and a gastroenterologist at the University Hospital of South Manchester, UK. He has been researching and treating patients with irritable bowel syndrome (IBS) for more than 35 years, and has seen the depths of despair that this condition can cause.

For years, researchers have tried to find biomarkers that could aid the diagnosis of irritable bowel syndrome, and point to its underlying causes. But will one test ever be enough?

Mishandling of patient information shows how governments and companies must become more worthy of trust, says Hetan Shah.

For cars to be safe, full control must be allocated to the driver — be it human or computer, argues John Baruch.

International audience; Crohn's disease (CD) and ulcerative colitis are the major forms of chronic inflammatory bowel diseases in the western world, and occur in young adults with an estimated prevalence of more than one per thousand inhabitants. The causes of inflammatory bowel diseases remain unknown, but genetic epidemiology studies suggest that inherited factors may contribute in part to variation in individual susceptibility to Crohn's disease. A genome-wide search performed on two consecutive and independent panels of families with multiple affected members, using a non-parametric two-point sibling-pair linkage method, identified a putative CD-susceptibility locus on chromosome 16 (P less than 0.01 for each panel). The localization was centered around loci D16S409 and D16S419 by using multipoint sibpair analysis (P less than 1.5x10(-5)). This region of the genome contains candidate genes which may be relevant to the pathogenic mechanism of inflammatory bowel diseases.

International audience; DNA recombinant technology has radically changed hepatitis B virus (HBV) virology. The genetic organization, transcription and replication of the virus are basically understood, structures of integrated HBV sequences in hepatocellular carcinoma have been characterized, and new vaccines produced by recombinant DNA technique are being developed.

THE bile pigment, giving the van den Bergh reaction with the diazo reagent in the absence of organic solvents, displays highly polar properties. Conjugated deoxycholic acid has been erroneously supposed to be a component which imparts to this pigment these properties (water-solubility, chloroform-insolubility, electrophoretic mobility, etc.)1. This statement was made on the basis of experiments with a preparation from bile containing a large excess of bile salts.

IN their recently published papers1,2, Heathcote and Mooney have expressed the belief that the concept of intrinsic factor is incorrect and that the absorption of vitamin B12 is dependent on gastric proteolysis. According to them, vitamin B12 is absorbed as either small peptide or amino-acid units. In addition, they reported excellent results of oral treatment of pernicious anaemia with a vitamin B12–glutamic acid mixture3.

No convincing evidence exists which demonstrates that mammalian thymus cells can directly express their immunological activity. It has been assumed, therefore, that the immunological role of the thymus is an indirect one, that is, that it supplies the ‘executive’ part of the immune machinery of the body with cells the replication of which may well be required to establish normal immune function. Nevertheless, the relationship of thymus cells to the plasma cells as well as to the population of small lymphocytes (which has been considered to be linked with several immune manifestations including tolerance1,2) is still obscure. A similar concept could be applied to the immunological function of the thymus in birds. However, some observations made in chickens have suggested that cells derived from the thymus might be properly qualified to induce directly an immune response or at least to participate in it3–7. This report provides some evidence to show that the thymus is capable of inducing a state of tolerance to skin homograft in the chicken.

THE authors of the preceding communication state that “According to them [Heathcote and Mooney], vitamin B12 is absorbed as either small peptide or amino-acid units”. We trust that this misinterpretation of our actual beliefs is due to lingual difficulty and does not imply that we believe in the peptide or amino-acid nature of vitamin B12 itself.

DAILY administration to rabbits of a desiccated whole bile preparation rapidly gives rise to cirrhosis of the liver1. Later findings suggested that the effect was linked to the activity of bile acids2 although several of the first tested and more common variants of them showed only a feeble liver damaging effect when used according to the present method2.