News & Views in 2021

Although nonalcoholic fatty liver disease is the most prevalent liver disease worldwide, there is a paucity of good-quality data on its natural history and most studies to date have reported on retrospective data. Robust data are required to inform regulatory end points, trial design and models of care.

Secretory immunoglobulin A (SIgA) regulates the composition and function of the gut microbiota and modulates its interaction with the host, but how this regulation is achieved is poorly understood. Now, Rollenske and colleagues profile the consequences of SIgA binding to the gut microbiota. They suggest that parallel generic and unique epitope-specific effects of SIgA regulate the intestinal microbiota.

Dietary fibre supports gut health and microbial ecology. Thus, characterizing the effects of inadequate fibre and intake of specific fibre formulations on the gut microbiome provides necessary information to move us towards diet–microbiome target treatments to support health.

Gene editing to correct inherited liver disorders has promise for future therapeutic intervention, but lack of effective and safe delivery of the gene-editing machinery to hepatocytes complicates its clinical application. Two studies now report efficient delivery to the liver of non-human primates, providing proof of concept for novel treatment of inherited hypercholesterolaemia.

Colorectal cancer screening has a large potential to reduce incidence and mortality, and screening programmes have been implemented in many countries and regions. Emerging epidemiological trends and evidence on the effectiveness and cost-effectiveness of various screening options call for regular updates of screening recommendations.

Delineation of fibroblast heterogeneity has the potential to identify select mesenchymal populations involved in health and disease. A recent study integrated single-cell transcriptomic data to generate a fibroblast atlas of steady-state and perturbed tissues in mice and humans, showing baseline and context-specific fibroblast phenotypes between species and pathologies, including IBD.

Cholangiopathies account for a remarkable proportion of liver transplantation cases, reinforcing the need for novel therapeutic approaches. Organoids hold great promise as novel cell-based therapies, although their applicability has not been addressed in humans. Now, a new study has reported the therapeutic effectiveness of cholangiocyte organoids to repair the injured human biliary epithelium.

Studies of liver regeneration after injury have provided knowledge of the role of external signals and internal metabolic and regenerative pathways. However, less is understood about homeostatic maintenance of normal liver size in the absence of external injury. Three important new studies explore liver regeneration and homeostasis using novel lineage tagging of hepatic cells and single-cell RNA transcriptomics.

Intense research is ongoing to dissect the reciprocal interactions between microbiota and drugs. New work finds that a drug to dampen host inflammation can also have off-target effects on the microbiota at transcriptional, metabolic and compositional levels, with resultant expanded benefits to the host.

The prevalence of nonalcoholic fatty liver disease (NAFLD) has increased rapidly and is associated with obesity in epidemiology and pathogenesis. A new study reports that hepatic and extrahepatic complications can develop in lean individuals with NAFLD, highlighting the importance of metabolic phenotypes in NAFLD assessment instead of BMI-based approaches.

Necrotizing enterocolitis (NEC) is an acute intestinal emergency in preterm infants, which is often later complicated by cognitive delay and neurodevelopmental disability. A new study performed in mice suggests that CD4⁺ T cells can travel from the NEC-inflamed gut to the brain and cause IFNγ-mediated brain injury.

Inflammatory bowel disease (IBD) has emerged as a global disease, yet identifying those at higher risk of developing IBD remains challenging. A new study highlights the use of a multi-ethnic polygenic risk score to determine risk of inflammatory bowel disease in a large primary care population.

A new study elevates our understanding of how the immune system regulates the pathogenesis of biliary atresia through a powerful single-cell approach. Cell-specific transcriptome analyses indicate key roles for macrophages, T cells and B cells in hepatobiliary injury of affected infants.