Review, News & Views, Perspectives, Hypotheses and Analyses in 2018

Innovative solutions are needed to overcome the global disparity in patients awaiting kidney transplantation versus donor organs available. A new study reports a promising new strategy of transplanting kidneys from HCV-infected donors into HCV-uninfected recipients and treating their HCV with direct-acting antivirals post-transplant — recipients achieved HCV cure with excellent one-year kidney allograft function.

New findings show that a gut microbiome signature derived from metagenomic and phenomic data can accurately predict nonalcoholic fatty liver disease (NAFLD) in obese women. The data highlight a role for phenylacetic acid, a microbial product of aromatic amino acid metabolism, in the cross-talk between the gut microbiome and the host hepatic phenotype.

Pancreatic cancer is a disease with high tumour heterogeneity and dismal prognosis. There are few therapeutic options and many promising drugs have failed in patients, which makes better models to predict drug efficacy a key research priority. Now, a new study shows that patient-derived organoids can be used for molecular and therapeutic profiling and might be useful to predict clinical responses.

A new report in Science by Ma and colleagues uncovers the interplay of microbiota-controlled bile acid metabolism and immune responses in the context of primary and metastatic liver tumours in mice. Their findings shed light on the gut–liver axis in hepatic malignancies.

IBD is associated with disruptions to resident microbial populations and inflammatory immune responses; however, little is known about how bacteria influence pathogenic immunity. New research identifies microbially produced ascorbate as a potential drug target to ameliorate disease by inhibiting inflammatory T cell function through altered cellular metabolism.

New findings show that disease-specific T cells that target gluten in patients with coeliac disease persist for decades. The data highlight a central role for a highly select and stable population of T cells in disease persistence and support the feasibility of diagnostics and therapies targeting these cells.

Serrated polyps contribute substantially to the development of colorectal cancer. Unfortunately, our knowledge of the molecular events that drive these lesions is limited. Now, a new study describes an organoid-based mouse model that might accelerate our understanding of the serrated neoplasia pathway.

Recurrence of hepatocellular carcinoma after resection or ablation with curative intent is common and not prevented by direct-acting antiviral agent (DAA) therapy for hepatitis C. Owing to multiple methodological inconsistencies, available studies fail to answer whether DAA therapy anticipated risk of severe tumour recurrence: a prospective randomized study might serve the purpose.

In a new study, Maier et al. reveal that non-antibiotic drugs intended to target human cells have off-target effects on the growth of human gut bacteria at clinically relevant concentrations. These results emphasize the need for a new field of metagenomic toxicology aimed at a more comprehensive understanding of the toxicity of compounds for humans and their associated microbial communities.

Colorectal cancer screening can save lives but there is a need for targeted, personalized screening. A new study examines an individual risk assessment based on family history, lifestyle, environmental and genetic factors, but faecal haemoglobin levels and their change over time can also help to further identify patients at high risk.

The efficacy of Helicobacter pylori eradication therapy for the prevention of preneoplastic lesions in gastric cancer remains controversial. A new placebo-controlled trial and a large-scale observational study tackle this problem and show the positive effects of eradication therapy.

Mechanical forces are important for normal gastrointestinal development and function. Now, He et al. have discovered a population of Drosophila midgut epithelial enteroendocrine cell (EEC) precursors that express the mechanosensitive ion channel Piezo, which generates a calcium influx that drives EEC differentiation and proliferation in response to physiological mechanical stimuli.

Rapid urbanization in the developing world has been associated with an increasing incidence of several autoimmune diseases. This Perspective discusses the effect of urbanization and its surrogates on the gut microbiome in both human health and IBD and how such changes might be associated with the development of IBD.

Exome sequencing of patients with Crohn’s disease (CD) of Ashkenazi Jewish descent and genotyping of large case–control cohorts has identified new CD risk and protective variants of LRRK2, the most common genetic determinant of Parkinson disease. These findings provide new insights into the pathophysiology of these two seemingly unrelated disorders.

Psychosocial risk factors (often linked to the gut–brain axis) are prevalent across different gastrointestinal disorders. Here, Keefer discusses the emerging field of psychogastroenterology and how behavioural medicine and the promise of positive psychology (resilience, optimism and self-regulation) could improve patient management.

In a prospective study of adults with Crohn’s disease or ulcerative colitis, Gracie and colleagues have found evidence for the bi-directional relationship between inflammatory bowel disease (IBD) activity and symptoms of psychological disorders. This study represents an important milestone in our understanding of how the brain and gut interact in IBD.

Although metagenomic sequencing has provided unprecedented characterization of the gut microbiome, it gives only indirect evidence of the genes and pathways that might be active. Now, investigators have combined longitudinal sampling with metatranscriptomics and metagenomics in IBD to provide a high-resolution picture of the microbiome's functional dynamics.

RNA interference (RNAi) is a novel concept to target transcripts derived from HBV covalently closed circular DNA. The study by Wooddell et al. investigates the RNAi-based therapy ARC-520 in patients and chimpanzees with chronic HBV infection and uncovers HBV DNA integration as a crucial source of hepatitis B surface antigen, which has not been considered in current strategies to accomplish HBV cure.

Increased relative abundance of Fusobacterium species contributes to the difference in intestinal bacterial composition between healthy individuals and patients with colorectal cancer (CRC). A new study now reveals that live Fusobacterium originating from primary CRC associate with liver metastasis, suggesting a potentially important function for this bacterial genus in metastatic tumour growth.

Predicting clinical outcomes in cancer using neoantigen burden is imperfect because current algorithms use only the binding affinity of putative neoantigens to HLA. A new study models pancreatic tumour response through a deeper understanding of tumour immunology, providing new tools for identifying neoantigens and characteristics that define their quality.