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Oxidative stress has been described as one of the main drivers of intracellular damage and metabolic disorders leading to metabolic syndrome, a major health problem worldwide. In particular, free radicals alter lipid metabolism and promote lipid accumulation in the liver, existing in the hepatic facet of metabolic syndrome, the metabolic dysfunction-associated steatotic liver disease (MASLD). Recent literature has highlighted how nicotine, especially if associated with a high-fat diet, exerts a negative effect on the induction and progression of MASLD by upregulating inflammation and increasing oxidative stress, abdominal fat lipolysis, and hepatic lipogenesis. Moreover, considerable evidence shows the central role of intestinal dysbiosis in the pathogenesis of MASLD and the impact of nicotine-induced oxidative stress on the gut microbiome. This results in an intricate network in which oxidative stress stands at the intersection point between gut microbiome, nicotine, and MASLD. The aim of this review is to delve into the molecular mechanisms linking tobacco smoking and MASLD, focusing on nicotine-induced microbiota modifications and their impact on MASLD development.

Inflammatory bowel diseases (IBDs) are intricate systemic conditions that can extend beyond the gastrointestinal tract through both direct and indirect mechanisms. Sarcopenia, characterized by a reduction in muscle mass and strength, often emerges as a consequence of the clinical course of IBDs. Indeed, sarcopenia exhibits a high prevalence in Crohn’s disease (52%) and ulcerative colitis (37%). While computed tomography and magnetic resonance imaging remain gold-standard methods for assessing muscle mass, ultrasound is gaining traction as a reliable, cost-effective, and widely available diagnostic method. Muscle strength serves as a key indicator of muscle function, with grip strength test emerging nowadays as the most reliable assessment method. In IBDs, sarcopenia may arise from factors such as inflammation, malnutrition, and gut dysbiosis, leading to the formulation of the ‘gut–muscle axis’ hypothesis. This condition determines an increased need for surgery with poorer post-surgical outcomes and a reduced response to biological treatments. Sarcopenia and its consequences lead to reduced quality of life (QoL), in addition to the already impaired QoL. Of emerging concern is sarcopenic obesity in IBDs, a challenging condition whose pathogenesis and management are still poorly understood. Resistance exercise and nutritional interventions, particularly those aimed at augmenting protein intake, have demonstrated efficacy in addressing sarcopenia in IBDs. Furthermore, anti-TNF biological therapies showed interesting outcomes in managing this condition. This review seeks to furnish a comprehensive overview of sarcopenia in IBDs, elucidating diagnostic methodologies, pathophysiological mechanisms, and clinical implications and management. Attention will also be paid to sarcopenic obesity, exploring the pathophysiology and possible treatment modalities of this condition.

As our comprehension of the pathogenic mechanisms of inflammatory bowel disease (IBD) increases, the therapeutic armamentarium for its treatment can expand, and novel target therapies join the treatment pipeline. Interleukin (IL)-12 and IL23 are two key cytokines responsible for promoting and perpetuating bowel inflammation in IBD. Ustekinumab is a monoclonal antibody directed against the shared p40 subunit of both cytokines, and it was recently approved for the treatment of ulcerative colitis (UC). In the pivotal phase III UNIFI trial, ustekinumab showed a superiority over placebo in both clinical and endoscopic outcomes; furthermore, it was characterized by a favorable safety profile, with a similar rate of adverse events as compared with placebo. Recent evidence from real-life experiences have started accumulating, generally confirming the effectiveness and safety figures emerged from the registration studies. However, most of these observational studies enrolled multirefractory patients; moreover, comparative data with other target therapies are lacking, leaving physicians without clear indications about the appropriate positioning of ustekinumab in the therapeutic pipeline for UC. This review examines the basis of targeting IL12-23 in UC therapy and summarizes the data from both clinical trials and real-life studies, to highlight the main evidence already available and the research gaps that need to be filled for the optimal usage of ustekinumab in UC.