Year in Review

2023 was the most memorable year on record for obesity. The American Academy of Pediatrics recognized the complex, multifactorial nature of obesity and the broad range of treatments necessary to care for pediatric patients. The first-ever triple agonist and high-potency oral GLP1 agonist was introduced with unprecedented results.

In 2023, there were significant advancements in trials of interventions to reduce mortality and morbidity from alcohol-related liver disease, spanning the entire spectrum of disease: primary prevention to reduce overall alcohol-related harm, secondary prevention to attenuate fibrosis progression and tertiary prevention using antibiotics for severe alcohol-associated hepatitis.

Metastatic colorectal cancer is a heterogeneous disease associated with poor patient outcomes. Although the past decade has seen few first-line treatment advances, key studies published in 2023 established new options for late-line therapy of the disease with and without oncogenic drivers, thus expanding the continuum of care in metastatic colorectal cancer.

Important studies published in 2023 outlined new agents and strategies for the management of inflammatory bowel disease. Therapeutic ambitions for the management of inflammatory bowel disease were raised by the success of combinations of biologic agents in ulcerative colitis and early surgical resection in Crohn’s disease.

New light is being shed on the interactions between the gut microbiome, cancer cell signalling and the host immune response. With this knowledge, microbiota-based approaches for improving cancer prevention, prognostication and therapy have started to materialize and will contribute to reducing the global cancer burden.

In 2023, we witnessed advances in allocation policies and marginal donors, including living donors. Key improvements included the uncapped Model for End-stage Liver Disease 3.0 score, unveiled machine perfusion trials to standard deceased donors and lessons from the aborted living donor liver transplantations.

Enteric nervous system function is essential for survival. Studies published in 2023 have provided important novel insights into the mechanisms that regulate its development and maintenance, and demonstrate how it can be restored when these mechanisms fail.

Key studies published in 2022 highlight the emergence of several novel drugs for inflammatory bowel disease. Head-to-head trials and network meta-analyses have also been conducted to identify the sequencing of these treatments, but we still have a long way to go to achieve personalized medicine.

The gut microbiome field is shifting from association to modulation. Microbiota-based treatments come in many shapes and sizes, ranging from dietary intervention to live bacterial products. Recent methodological advances are instrumental to developing innovative new treatment strategies in microbiome-linked pathologies.

The year 2022 was notable for substantial research progress related to pancreatic ductal adenocarcinoma (PDAC). The first single-cell and spatial transcriptomic atlases of PDAC were reported, a mechanism for how Schwann cells promote perineural invasion was explored, and, finally, the role of exercise in abrogating immunosuppression was shown.

Various pathways enable communication between the gut and brain, and this communication influences physiology and behaviour. Studies published in 2022 demonstrate how our understanding of several of these pathways is advancing rapidly.

In 2022, we witnessed advances in the field of alcohol-related liver disease. Key developments included the discovery of novel proteomics-based biomarkers and potential therapeutic targets that regulate the recognition of molecules derived from gut microbiota to modulate liver injury. Additionally, there have been significant advances in refining selection for liver transplantation in severe alcohol-associated hepatitis.

2022 was a proficuous year in both the nonalcoholic fatty liver disease (NAFLD) and obesity fields. Pharmacological treatment for obesity and NAFLD is moving forward, with the possibility of replacing bariatric surgery, artificial intelligence might help us access the histological effects of new drugs, and there were advances in personalized hepatocellular carcinoma screening in patients with NAFLD.

Key studies published in 2022 further established the importance of alterations in the gut microenvironment and interactions with the enteric and central nervous systems in symptom generation in irritable bowel syndrome and suggested novel and clinically accessible therapeutic approaches for this large group of patients.

Vaccination is a key intervention for the elimination of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections to fulfil the WHO’s 2030 global elimination goal. Innovations in 2021 promise to curb HBV transmission by reducing mother-to-child transmission and enhancing vaccine immunogenicity in at-risk adult groups. Additionally, an HCV vaccination trial was conducted, and there were also advances in our understanding of the immunology underpinning the lack of protection against HCV reinfection.

Important colorectal cancer (CRC) studies in 2021, including a new standard of care for first-line treatment of MSI-H–dMMR metastatic CRC, single-cell and spatial analysis of primary tumours and investigations of diet in preclinical models of cancer initiation, have provided novel insights into the CRC immune microenvironment.

Important studies in 2021 demonstrated sophisticated developments in the study of liver fibrosis through omics. Cell-specific mapping, single-cell sequencing and deep-learning systems revealed complex intra-hepatic mechanisms and new computational platforms facilitating the research towards drug discovery in liver disease and in fibrosis.

2021 has been a productive year for fungal research. Key studies focused on intestinal inflammation and inflammatory bowel disease highlight antibody-mediated immunity in control of fungal commensalism, commensal and dietary fungi in intestinal inflammation and wound healing, and the therapeutic potential of transgenic yeast engineered to sense and target factors during intestinal inflammation.

Key studies published in 2021 demonstrated mechanisms that drive macrophage–fibroblast pathogenicity in Crohn’s disease, developed multi-omics profiles to predict response to biological therapy, and suggested potential complementary treatments and new therapeutic agents in inflammatory bowel disease (IBD) therapy. These results represent important progress towards precision medicine for patients with IBD.

In 2021, transcriptome analysis of the mouse and human gut advanced our understanding of the cellular composition, development and surrounding non-neural context of the enteric nervous system (ENS). A role for the ENS in tuning regulatory T cell proportions contributed insights into the dependency between the ENS, immune system and microbiota.