Reviews & Analysis

Live biotherapeutics have been used clinically both as defined probiotics and as undefined faecal microbiota transplants. Two new studies illustrate the risks of administering live microorganisms to highly compromised patients. These risks should be considered in the context of the potential therapeutic value of these treatments.

Key studies published in 2019 highlight novel concepts regarding the pathogenesis of inflammatory bowel disease: the emerging role of host–microorganism interactions and the regional microbiota as disease drivers, and the identification of new therapeutic targets. These findings suggest new avenues for research and define important hallmarks for clinical diagnosis and therapy.

Primary biliary cholangitis (PBC) is a chronic, inflammatory and cholestatic liver disease with a variable rate of progression towards biliary cirrhosis. Here, the authors discuss the current understanding of PBC pathogenesis and highlight implications for new therapies.

Key studies published in 2019 shed new light on how complex motor patterns emerge from the functional organization of circuits in the enteric nervous system and, in turn, how extrinsic afferent neurons and common commensal microorganisms interface with these circuits to modulate intestinal motility.

An area of research suggests a role for microbiota in the pathogenesis of pancreatic diseases, such as pancreatitis, pancreatic cancer and type 1 diabetes mellitus. In this Perspectives, the authors examine the literature implicating microorganisms in diseases of the pancreas as well as the evidence of an inherent pancreatic microbiota.

This Review discusses the molecular heterogeneity of hepatocellular carcinoma, the intrinsic and extrinsic factors that stimulate tumour evolution and how this information can be leveraged to improve the clinical management of patients with this disease.

In 2019, there have been substantial advances in our understanding of the gut microbiome. Key developments include an improved gut-on-a-chip system, a search for small proteins produced by the commensal gut microbiome and the publication of one of the most comprehensive multi-omic datasets for interrogating host–microorganism interactions in inflammatory bowel disease.

IBD treatment has an expanding repertoire of drugs targeting different aspects of the immune response. This Review focuses on unravelling the complexity of mucosal immune responses in IBD pathogenesis and how analytical assays might be harnessed to effectively stratify and individualise IBD therapy.

Advances have been made in the field of nonalcoholic fatty liver disease in 2019. One paper highlights the role of gut microbiota in hepatocellular carcinoma (HCC) pathogenesis, another presents a noninvasive algorithm for detecting advanced liver fibrosis and another suggests a potential novel approach to treating nonalcoholic steatohepatitis and suppressing HCC development.

In 2019, powerful single-cell analyses were applied to liver cancer biology at an unprecedented level. In parallel with this achievement was the identification of serum α-fetoprotein as a biomarker for patient selection in the use of ramucirumab for liver cancer and that β-catenin activation can distinguish between liver cancer immunotherapy responders and non-responders.

Functional constipation is common in children and adults worldwide. Here, the authors provide an overview of the differing management strategies for childhood and adult functional constipation, including insights into epidemiology, pathophysiology, diagnosis and therapy.

A new study demonstrates a novel role for an endocannabinoid in promoting hepatocyte steatosis. The study describes a mode of bidirectional communication between the alcohol-injured hepatocyte and the glutamate-activated hepatic stellate cell. This intercellular communication represents a novel targetable pathogenic mechanism that could lead to new strategies to prevent fatty liver disease progression to cirrhosis.

Primary liver cancers are frequently accompanied by rearrangements of metabolic pathways. This Review discusses the role of metabolic liver disruptions and the implications of these processes, emphasizing their clinical relevance and value in early diagnosis and prognosis and as putative therapeutic targets.

This Review discusses the genetics of nonalcoholic fatty liver disease (NAFLD), including evidence of shared genetic modifiers and possible pleiotropic effects between NAFLD and other liver diseases or metabolic disorders. The translational implications and future challenges are also discussed.

A new study reveals that a novel serotonin sensor in the spore-forming gut bacteria, Turicibacter sanguinis, might be important for host lipid and steroid metabolism. These findings support the emerging concept that bidirectional signalling pathways can influence bacterial community structure and exert effects on host physiology.

A new study is the first to investigate the relationship between liver-enriched antimicrobial peptide-2 (LEAP2) and different metabolic states, and highlights the reciprocal relationship between LEAP2 and ghrelin (known as the ‘hunger hormone’ for its role in stimulating appetite). These findings could have important implications given the worldwide increase in obesity since 1975.

Innate immune responses are currently seen as a key element driving hepatic inflammation in nonalcoholic steatohepatitis. However, this Review discusses the increasing evidence pointing to the role of adaptive immunity as an additional factor promoting liver inflammation and driving disease progression.

Screening and early diagnosis of pancreatic cancer are at the focal point of attention from researchers, physicians and patients. A new systematic review and recommendation statement by the USPSTF attempt to summarize the current state of affairs.

In this Viewpoint article, we asked a selection of scientists and clinicians in the gut microbiota field to provide their opinions on the major advances in and future directions for research, and the challenges and solutions for translating gut microbiome research to the clinic.

Colorectal cancer (CRC) is one of the most common cancers worldwide. This Review describes the role of microorganisms in colorectal carcinogenesis, and the potential clinical translation of the gut microbiota as a biomarker for CRC diagnosis and prognosis, and as an approach for disease prevention and to improve therapy.