As the global population ages, research on the biology of ageing and its role in chronic disease is expanding, alongside a growing clinical focus on the unique needs of older adults. In the past, the liver was not though...As the global population ages, research on the biology of ageing and its role in chronic disease is expanding, alongside a growing clinical focus on the unique needs of older adults. In the past, the liver was not thought to undergo substantial age-related changes, nor was there thought to be any liver disease characteristic of older adults. Current studies challenge this perspective, revealing that ageing substantially influences liver pathophysiology at the organ level and within each of the liver cell types. These observations have implications for understanding the pathogenesis of liver diseases common in older adults, including hepatocellular carcinoma, hypoxic hepatitis and metabolic dysfunction-associated steatotic liver disease. Previously, managing older patients with liver disease mostly addressed age-related changes in drug metabolism and liver function tests. However, current clinical practice increasingly emphasizes age-specific issues such as frailty, sarcopenia, multimorbidity and polypharmacy. Given the liver's pivotal role in systemic metabolism, immunity and detoxification, ageing of the liver can contribute to systemic diseases. In the future, interventions that target ageing biology might offer new treatment options for liver diseases. Here, we review those age-related changes in the liver that have substantial biological and clinical consequences for older adults.
Colorectal cancer (CRC) remains a substantial public health challenge globally and is the second leading cause of cancer-related death in the USA. Despite advances in screening and treatment, disparities in CRC outcomes...Colorectal cancer (CRC) remains a substantial public health challenge globally and is the second leading cause of cancer-related death in the USA. Despite advances in screening and treatment, disparities in CRC outcomes persist, especially among Black individuals in the USA, who face higher CRC incidence and mortality and lower survival compared with White individuals. Inequities are largely attributed to social determinants of health (SDOH), such as access to health care, socioeconomic conditions and systemic inequities. In this Review, we examine Black-White disparities in CRC outcomes across the CRC care continuum in the USA, highlighting contributing modifiable (non-biological) and non-modifiable (biological) risk factors. We also discuss successful interventions that have reduced or eliminated disparities. Existing evidence suggests that Black-White differences in CRC screening participation, CRC incidence and CRC mortality can be resolved. Future efforts must emphasize improving access to screening and guideline-concordant treatment to achieve progress in the near term while addressing the underlying and historical SDOH that drive inequities to eliminate disparities in the long term. The Review underscores the need for sustained investment in addressing both immediate and systemic barriers to CRC screening and care in Black communities to eliminate disparities in CRC outcomes and improve the overall health of the nation.
Inflammatory bowel disease (IBD) is a global condition that progresses through four epidemiologic stages: emergence, acceleration in incidence, compounding prevalence and prevalence equilibrium. Early industrialized coun...Inflammatory bowel disease (IBD) is a global condition that progresses through four epidemiologic stages: emergence, acceleration in incidence, compounding prevalence and prevalence equilibrium. Early industrialized countries are currently in the compounding prevalence stage before transitioning to the prevalence equilibrium stage, with >1% of their populations expected to live with IBD within the next decade. Prevalence equilibrium can be modelled using a health-illness-death compartment framework and partial differential equations to predict prevalence to 2045. Meanwhile, newly industrialized countries are projected to shift from accelerated incidence with low prevalence to compounding prevalence over the next two decades. This Perspective explores the global evolution of IBD through these epidemiologic stages, presenting a framework for disease prevention and innovative health-care strategies to address the critical challenges the global IBD community will face over the next 20 years.
Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, incl...Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most prevalent chronic liver disease worldwide, affecting billions of the global population. It can gradually progress to more severe diseases, including steatohepatitis, cirrhosis and hepatocellular carcinoma. Studies have highlighted the importance of the gut microbiome in the pathogenesis and progression of MASLD. On the other hand, increasing evidence has revealed the clinical potential of targeting the gut microbiome to treat MASLD. In this Review, we summarize gut microbial alterations in MASLD, metabolic dysfunction-associated steatohepatitis and hepatocellular carcinoma. The mechanisms by which a dysregulated gut-liver axis contributes to disease progression are also described, including intestinal barrier dysfunction, chronic inflammation, and altered metabolic pathways (for example, bile acids) and microbial-derived metabolites (for example, short-chain fatty acids, tryptophan derivatives and endogenous ethanol). In addition, we discuss the clinical implications of utilizing the gut microbiome as a diagnostic biomarker and the therapeutic approaches to treat MASLD and related diseases such as faecal microbiota transplantation, probiotics and engineered bacteria, prebiotics and postbiotics, microbial-derived metabolites, antimicrobials and bacteriophages. Finally, we discuss current challenges in basic and translational research on the microbiome in MASLD and propose future directions to drive progress in this field.
In the human gastrointestinal tract, pH is a key factor in shaping gut microbial composition and activity, while also being influenced by microbial metabolism. pH varies substantially along the gastrointestinal tract wit...In the human gastrointestinal tract, pH is a key factor in shaping gut microbial composition and activity, while also being influenced by microbial metabolism. pH varies substantially along the gastrointestinal tract within an individual and between different individuals due to a combination of host, diet, microbial and external factors. The importance of pH on microbiota composition and metabolic response has been widely explored over the past century. Here, we review the literature to explore the major physiological and dietary factors that influence pH along the gastrointestinal tract. From a microbial ecology perspective, we discuss how gastrointestinal pH affects microbiota composition and metabolism. We explore mechanisms by which pH can influence bacterial acid response systems, gene expression and the production of microbial metabolites important for health. Finally, we review the literature regarding the potential role of gastrointestinal pH in human diseases. We propose that we can advance our understanding of the gut microbiota in health and disease by considering gastrointestinal pH. We argue that pH-mediated gut microbial metabolic variation is highly important for predicting and manipulating metabolic output relevant to human health.
Rochman M, Kellerman K, Jankowski MP
… +1 more, Rothenberg ME
Nat Rev Gastroenterol Hepatol
· 2025 Sep · PMID 40533621
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The oesophagus has traditionally been viewed as a simple conduit for food transport. In performing this delivery function, it confronts a continuous influx of foreign antigens, including food particles with variable micr...The oesophagus has traditionally been viewed as a simple conduit for food transport. In performing this delivery function, it confronts a continuous influx of foreign antigens, including food particles with variable microbial content, and encounters many biophysical stimuli triggered by food textures and temperature. To meet these challenges, the oesophagus comprises a robust barrier featuring a thick, multilayered epithelium coated by mucins and mechanically held together by strong adhesion complexes, including desmosomal junctions. Sentinel immune cells, including a notable presence of CD8 resident memory T cells, mast cells and dendritic cells, are abundant alongside IL-1 family cytokines released and activated under tight homeostatic regulation through a balance of proteases and antiproteases. Pattern recognition receptors, such as Toll-like receptors on epithelial cells, identify foreign antigens and can trigger cytokine release. Disruptions, whether acquired or genetically inherited, in these innate immune functions contribute to disease onset. Here, we present evidence that the oesophagus is an immune organ with extensive sensing properties designed to tolerate and mount defences against antigenic and biophysical challenges.