The gut microbiome has an undeniable role in mediating the health effects of the diet, given its ability to co-digest nutrients and influence nutrient signalling to multiple organ systems. As a suboptimal diet is a major...The gut microbiome has an undeniable role in mediating the health effects of the diet, given its ability to co-digest nutrients and influence nutrient signalling to multiple organ systems. As a suboptimal diet is a major risk factor for and contributor to disease, understanding the multidirectional interactions between the food we eat, the gut microbiome and the different body organ systems is crucial from a public health perspective. Indeed, this research area is leading to the refinement of nutritional concepts and strategies to optimize health through diet. In this Review, we provide an update on how dietary patterns and food intake shape gut microbiome features, the mode of action of diet-microorganism interactions on the immune, nervous and cardiometabolic systems and how this knowledge could explain the heterogeneity of dietary responses, and support food-based dietary guidelines and medical and precision nutrition. Finally, we discuss the knowledge gaps and research efforts needed to progress towards the integration of microbiome science with more precise dietary advice to leverage the role of nutrition in human health.
Alcohol-related liver disease (ALD) is a major cause of morbidity and premature mortality around the world, with a substantial cost to individuals and to health-care systems. The incidence of ALD is closely associated wi...Alcohol-related liver disease (ALD) is a major cause of morbidity and premature mortality around the world, with a substantial cost to individuals and to health-care systems. The incidence of ALD is closely associated with alcohol intake, and it is a preventable disease. There is clear evidence that public health measures to reduce alcohol consumption are effective, which in turn can have a positive effect on ALD. Effective policy includes controlling the price of alcohol, limiting or banning alcohol advertising and restricting the availability of alcohol. The strength of public health policy depends on the political willingness to develop robust strategies. However, effective lobbying of policy-makers by the alcohol industry and lack of political will are barriers to the implementation of these measures, resulting in suboptimal national alcohol control policies. Clinicians are well-placed to campaign for effective public health policy regarding alcohol to reduce the prevalence of ALD for the benefit of patients, their families and wider society. In this Perspective, we summarize the evidence for public health policies that affect alcohol consumption and the prevalence of ALD.
Menopause has far-reaching effects on human physiology, including the gastrointestinal tract, and can negatively influence the quality of life of women who are affected. Menopause can have multiple effects on gastrointes...Menopause has far-reaching effects on human physiology, including the gastrointestinal tract, and can negatively influence the quality of life of women who are affected. Menopause can have multiple effects on gastrointestinal function, including altering gut motility and changing the composition of the gut microbiota. As a result, some gastrointestinal and hepatic conditions are more common among individuals in peri- and postmenopause, and people with these conditions before menopause might also experience greater symptom severity and worse health-related quality of life during this time. The use of hormone replacement therapy to treat menopausal symptoms might also affect gastrointestinal health and well-being. Individuals in postmenopause are at risk for bone remodelling and osteoporosis due to ageing and loss of sex hormones. However, secondary osteoporosis can also occur due to medications used to treat gastrointestinal conditions (for example, glucocorticoids and other immunosuppressive medications) and the conditions themselves (for example, autoimmune disease or coeliac disease). Although all people who menstruate will eventually transition to menopause, there are relatively few studies evaluating the effect of menopause on gastrointestinal symptoms and quality of life. This Review aims to summarize available evidence and highlight areas where research is needed.
In the past decades, the pathogenic role of hepatic stellate cells (HSCs) in the development of liver fibrosis and its complications has been deeply characterized, rendering HSCs a primary target for antifibrotic therapi...In the past decades, the pathogenic role of hepatic stellate cells (HSCs) in the development of liver fibrosis and its complications has been deeply characterized, rendering HSCs a primary target for antifibrotic therapies. By contrast, the beneficial roles of HSCs in liver homeostasis and liver disease are only beginning to emerge, revealing critical regulatory and fibrosis-independent functions in hepatic zonation, metabolism, injury, regeneration and non-parenchymal cell identity. Here, we review how HSC mediators, such as R-spondin 3, hepatocyte growth factor and bone morphogenetic proteins, regulate critical and homeostatic liver functions in health and disease via cognate receptors in hepatocytes, Kupffer cells and endothelial cells. We highlight how the balance shifts from protective towards fibropathogenic HSC mediators during the progression of chronic liver disease (CLD) and the impact of this shifted balance on patient outcomes. Notably, the protective roles of HSCs are not accounted for in current therapeutic concepts for CLD. We discuss the concept that reverting the HSC balance from fibrogenesis towards hepatoprotection might represent a novel holistic treatment approach to inhibit fibrogenesis and restore epithelial health in CLD simultaneously.
Costa DVS, Thomasi B, Brito GAC
… +2 more, Gulbransen BD, Warren CA
Nat Rev Gastroenterol Hepatol
· 2025 Aug · PMID 40404838
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Clostridioides difficile is the leading cause of antibiotic-associated diarrhoea worldwide. In the USA, C. difficile infection (CDI) is the eighth leading cause for hospital readmission and seventh for mortality among al...Clostridioides difficile is the leading cause of antibiotic-associated diarrhoea worldwide. In the USA, C. difficile infection (CDI) is the eighth leading cause for hospital readmission and seventh for mortality among all gastrointestinal disorders. Gastrointestinal dysmotility and/or diarrhoea occurs after the acute phase of CDI, but persistent gastrointestinal dysfunction post-infection supports contributions of neuroplasticity in the enteric nervous system (ENS), which has a key role in regulating intestinal motility and secretion, in the natural course of CDI. Here, our goal is to provide an up-to-date summary of how the ENS and extrinsic innervation of the gut are affected by CDI and how ENS responses contribute to CDI pathogenesis and outcomes. Enteric neurons and glia are targets of C. difficile toxins in humans and in preclinical model, and changes to the ENS and extrinsic innervation contribute to intestinal inflammation, damage and secretory diarrhoea. These findings suggest possible bidirectional interaction between CDI and the ENS. More studies focusing on understanding how various neurotransmitters and mediators released by the ENS and extrinsic neurons modulate immune responses to CDI could provide insight into novel pharmacological approaches to balance the host response, improve the management of CDI and prevent gastrointestinal dysfunction post-infection.
Despite an increase in our understanding of the pathophysiology of irritable bowel syndrome (IBS), in the context of abnormal gut-brain axis communication, and advances in both pharmacological and non-pharmacological tre...Despite an increase in our understanding of the pathophysiology of irritable bowel syndrome (IBS), in the context of abnormal gut-brain axis communication, and advances in both pharmacological and non-pharmacological treatment of the disorder, there remain areas in which there are misconceptions and controversies in the clinical management of IBS. This Perspective aims to highlight some of the most common misconceptions and controversies in IBS management, including those that the scientific literature has resolved, but for which further education of clinicians dealing with patients with IBS might be required to implement the findings from medical research. Areas of remaining contention are also discussed, as are suggestions as to how these issues could be addressed, both by advances in clinical practice and by further research.
Inflammatory bowel disease (IBD) is a growing global health challenge affecting more than 7 million people worldwide. With increasing prevalence across all age groups, including children and adolescents, IBD places subst...Inflammatory bowel disease (IBD) is a growing global health challenge affecting more than 7 million people worldwide. With increasing prevalence across all age groups, including children and adolescents, IBD places substantial strain on health-care systems and society, resulting in high direct medical costs, lost productivity and reduced quality of life. Despite therapeutic advances, suboptimal disease control and delays in timely diagnosis and adequate treatment persist. Regional disparities in health-care access contribute to these challenges, especially in low-income countries. Addressing these inequities is crucial for improving global IBD outcomes. Using a Delphi methodology, experts from clinical care, research, public health and advocacy (including patient representation) identified priorities across six domains (37 statements in total): epidemiology, care models, treatment strategies, education and awareness, patient and community engagement, and leadership to promote health equity. These priorities emphasize quantifying the burden of IBD, addressing health-care disparities, validating care models, exploring novel treatments, advancing education, engaging patients and advocating for health equity policies. The comprehensive approach seeks to optimize care models, promote patient engagement and ensure equitable access to health care. The identified priorities serve as a guide for both clinical and non-clinical researchers, and funders dedicated to IBD-related initiatives, fostering international collaboration to improve IBD management and reduce its impact globally.
Despite multimodal treatment options, most gastrointestinal cancers are still associated with high mortality rates and poor responsiveness to immunotherapy. The unprecedented efficacy of chimeric antigen receptor (CAR)-e...Despite multimodal treatment options, most gastrointestinal cancers are still associated with high mortality rates and poor responsiveness to immunotherapy. The unprecedented efficacy of chimeric antigen receptor (CAR)-engineered T cells in the treatment of haematological malignancies raised interest in translating CAR T cell therapies to the treatment of gastrointestinal cancers. Treatment of solid cancers with canonical CAR T cells faces substantial challenges, including the dense architecture of the tumour tissue, the tolerogenic environment with low tumour-intrinsic immunogenicity, the rareness of targetable tumour-selective antigens, the antigenic heterogeneity of cancer cells, and the profound metabolic and immune cell disbalances. This Review provides an overview of CAR T cell trials in the treatment of gastrointestinal cancers, discussing considerations relating to safety, efficacy, potential reasons for failure and options for improving CAR T cells for the future. In addition, lessons regarding how to improve efficacy are drawn from CAR T cells armed with adjuvants that sustain their activation within the hostile environment and activate resident immune cells. As the field is rapidly evolving, current treatment modalities and editing CAR T cell functionalities are being refined towards a potentially more successful CAR T cell therapy for gastrointestinal cancers.