Tumour-draining lymph nodes (TDLNs) serve as the closest immunological hubs to the primary tumour site in colorectal cancer (CRC). Owing to their unique and irreplaceable anatomical advantage and dynamic immune cell repertoire, TDLNs represent an intensively studied immunological niche and are a potential therapeutic target.

Mismatch repair-deficient (MMRd) colorectal cancers (CRCs) are highly mutated and immunogenic yet frequently escape immune elimination.

Cancer stem cells (CSCs) drive tumour initiation, metastasis and therapeutic resistance through metabolic and microenvironmental adaptability. The microbiota critically modulates cancer development and treatment response, with increasing evidence linking commensal microbes and their metabolites to aberrant CSC function. In this review, we summarise the mechanistic roles of microbiota and metabolites (eg, short-chain fatty acids, bile acids) in CSC regulation, including their effects on the CSC niche via stromal cell modulation, extracellular matrix remodelling and soluble factor networks. Given the central roles of CSCs in chemoresistance, we further discuss how microbes and metabolites influence CSC-associated chemotherapy resistance and highlight microbiota-targeting and metabolite-targeting strategies including probiotics, metabolite formulations, antibiotics and nanomedicine to disrupt CSCs and enhance chemosensitivity. In summary, deeper insights into CSC-microbiota-metabolites crosstalk promise novel therapeutic targets to overcome resistance and improve patient outcomes.

Pragmatic colorectal cancer (CRC) screening trials compare colonoscopy with faecal immunochemical testing (FIT), but differences in adherence complicate interpretation of comparative outcomes.

The prevalence of chronic kidney disease (CKD), defined as a glomerular filtration rate (GFR) of <60 mL/min/1.73 m2 for >3 months, is rising in the global population.

A resemblance of pancreatic tumours to their native tissue architecture remains largely unexplored, while it may reveal novel insights into healthy and diseased tissue.

Severe acute pancreatitis (SAP) is a life-threatening inflammatory disorder characterised by progressive multiorgan dysfunction. Direct investigation of human pancreatic tissue in SAP has been extremely limited, and effective targeted therapies are currently lacking.

At around 10 years ago, at the time of the first publication by the Gut Microbiota for Health Expert Panel of the British Society of Gastroenterology, recognition of the gut microbiome's importance in health and disease was transitioning from fringe interest towards major global pursuit. A decade on, we appraise the considerable progress made in the field, while acknowledging ongoing challenges. Earlier human work characterising the 16S rRNA gene amplicon signature of particular conditions in small cohorts has been superseded by larger, multicentre studies with extensive metadata. Studies increasingly employ shotgun metagenomics and other 'omic' techniques-coupled with refined bioinformatic tools and disease models-to better characterise perturbation in gut microbiome functionality. The arrival of 'gold standard' pipelines for microbiome analysis and increased mechanistic validation of signals are key developments towards more clinically-translatable outcomes. Novel clinical areas where the gut microbiome has relevance have emerged, including early life and the efficacy of certain treatments (including immune checkpoint inhibitors and vaccination). Enthusiasm for 'microbiome diagnostics and treatments' has grown, but barriers to widespread adoption remain. Faecal microbiota transplant (FMT) is established for treating recurrent Clostridioides difficile infection, with donor-derived 'next generation' FMT products licensed for this condition in certain countries. Beyond FMT, other microbial therapeutic techniques-including nutritional, bacteriophage and probiotic therapies-show promise, but have not fulfilled their high expectations yet. Gut microbiome research is now well-established and shows significant translational potential; the future focus will be translational work to drive its utility in clinical diagnostics, prognostics and therapeutics.

The human microbiota comprises a diverse and extensive community of microorganisms that participate in intricate interactions with the host, several of which are increasingly acknowledged as key modulators of health and disease. Among these, Fusobacterium nucleatum (Fn), an oral commensal bacterium, has emerged as a significant oncobacterium implicated in tumour progression. The Fn genus comprises distinct subspecies, clades and strains, exhibiting marked phylogenetic and physiological heterogeneity. Consequently, pinpointing the true functional modulators within this complex community and elucidating their mechanisms in various physio-pathological states remains a critical yet challenging endeavour. Moreover, the complete mechanism underlying Fn's function across different spatial locations and physiological states remains to be fully elucidated. This review details the genetic and phenotypic heterogeneity among Fn subspecies, which underlies their differential characteristics and niche adaptation. We further delineate key effectors of Fn, such as adhesins, metabolites and exoproteins, which collectively facilitate host cell invasion, immune evasion and chemoresistance induction. We explore the translational potential of Fn, underscoring its utility as a diagnostic biomarker and a promising target for novel therapeutic strategies.

Short bowel syndrome (SBS) is defined by a remaining small bowel length of less than 200 cm after surgical resection and is a condition with significant clinical implications and a high risk of developing chronic intestinal failure. However, our understanding of intestinal adaptation, a natural process to enhance absorption of nutrients and fluids after resection, remains limited. Intestinal adaptation occurs at both structural (eg, mucosal hyperplasia) and functional (eg, altered transit and enhanced epithelial transporter expression) levels, although most insights stem from animal research and the molecular mechanisms driving these processes are not yet fully understood. This review integrates current evidence on intestinal adaptation in patients with SBS and highlights the critical role of animal models in understanding the underlying mechanisms but also underlines the need for longitudinal studies in human patients. While the diversity of available animal models provides opportunities to investigate key pathways, the variability in residual intestinal length complicates our understanding of the molecular pathways. Based on existing data, we propose that intestinal adaptation is a time-dependent process, with the most pronounced changes occurring early after resection and is affected by the remaining anatomy of the GI tract. Advancing knowledge in these areas is essential for identifying novel therapeutic targets and improving outcomes for patients with SBS.

Chronic pancreatitis (CP) is a progressive fibroinflammatory disorder with persistent immune activation and limited therapeutic options. While physical activity (PA) benefits many chronic diseases, it is often presumed neutral or potentially harmful in CP.

Pancreatic ductal adenocarcinoma (PDAC) frequently invades adjacent peripancreatic adipose tissue, yet the role of tumour-infiltrating adipocytes (TIAs) in shaping antitumour immunity remains unclear.

Crohn's disease (CD) is a chronic inflammatory disorder of the gastrointestinal tract with high risk of surgery. Despite advances in medical treatment, of those patients who undergo ileocolonic resections, up to 70% of patients experience postoperative recurrence (POR) within 1 year of surgery. This underscores the need for a better understanding of the pathogenesis of POR. We hypothesise that the transient 'disease-free' state following surgical resection biologically mirrors the earliest preclinical stages of new-onset CD and that shared biomarkers across preclinical and postoperative settings reflect common pathogenic pathways. Identifying these shared signatures may offer a unique opportunity to elucidate mechanisms underlying both disease initiation and recurrence and to inform strategies aimed at prevention of new onset CD as well as POR. In this review, we synthesise insights from recent biomarker and multiomics studies spanning preclinical and postoperative CD cohorts. We highlight predictive biomarkers shared across CD onset and POR, including genetic variants, immune mediators such as CXCL9 and interleukin 6, microbial signatures involving Faecalibacterium and Ruminococcus and markers of gut barrier dysfunction and systemic inflammation. We also discuss emerging omics approaches including glycomics, urine metabolomics and high-dimensional immunophenotyping that may further refine risk stratification, capture pathogenic heterogeneity and provide mechanistic insight into host-microbe-immune interactions. Finally, we outline potential intervention strategies targeting these shared pathways and propose that the postoperative setting could be a pragmatic human model to test biomarker-guided preventive approaches applicable across the CD spectrum.