Inflammatory bowel diseases (IBDs) are characterized by a persistent low-grade inflammation that leads to an increased risk of colorectal cancer (CRC) development. Several factors are implicated in this pathogenetic pathway, such as innate and adaptive immunity, gut microbiota, environment, and xenobiotics. At the gut mucosa level, a complex interplay between the immune system and gut microbiota occurs; a disequilibrium between these two factors leads to an alteration in the gut permeability, called ‘leaky gut’. Subsequently, an activation of several inflammatory pathways and an alteration of gut microbiota composition with a proliferation of pro-inflammatory bacteria, known as ‘pathobionts’, take place, leading to a further increase in inflammation. This narrative review provides an overview on the principal Pattern Recognition Receptors (PRRs), including Toll-like receptors (TLRs) and NOD-like receptors (NLRs), focusing on their recognition mechanisms, signaling pathways, and contributions to immune responses. We also report the genetic polymorphisms of TLRs and dysregulation of NLR signaling pathways that can influence immune regulation and contribute to the development and progression of inflammatory disease and cancer.

By 2030, 30% of the European population will be aged 60 or over and those aged 80 and above will be the fastest growing cohort. An increasing number of people will die at an advanced age with multiple chronic diseases. In Europe at present, between 12 and 38% of the oldest people die in a long-term care facility. The lack of nationally representative empirical data, either demographic or clinical, about people who die in long-term care facilities makes appropriate policy responses more difficult. Additionally, there is a lack of comparable cross-country data; the opportunity to compare and contrast data internationally would allow for a better understanding of both common issues and country-specific challenges and could help generate hypotheses about different options regarding policy, health care organization and provision. The objectives of this study are to describe the demographic, facility stay and clinical characteristics of residents dying in long-term care facilities and the differences between countries. Epidemiological study (2015) in a proportionally stratified random sample of 322 facilities in Belgium, Finland, Italy, the Netherlands, Poland and England. The final sample included 1384 deceased residents. The sampled facilities received a letter introducing the project and asking for voluntary participation. Facility manager, nursing staff member and treating physician completed structured questionnaires for all deaths in the preceding 3 months. Of 1384 residents the average age at death ranged from 81 (Poland) to 87 (Belgium, England) (p < 0.001) and length of stay from 6 months (Poland, Italy) to 2 years (Belgium) (p < 0.05); 47% (the Netherlands) to 74% (Italy) had more than two morbidities and 60% (England) to 83% (Finland) dementia, with a significant difference between countries (p < 0.001). Italy and Poland had the highest percentages with poor functional and cognitive status 1 month before death (BANS-S score of 21.8 and 21.9 respectively). Clinical complications occurred often during the final month (51.9% England, 66.4% Finland and Poland). The population dying in long-term care facilities is complex, displaying multiple diseases with cognitive and functional impairment and high levels of dementia. We recommend future policy should include integration of high-quality palliative and dementia care.

The gut microbiota is central to the pathogenesis of several inflammatory and autoimmune diseases. While multiple mechanisms are involved, the immune system clearly plays a special role. Indeed, the breakdown of the physiological balance in gut microbial composition leads to dysbiosis, which is then able to enhance inflammation and to influence gene expression. At the same time, there is an intense cross-talk between the microbiota and the immunological niche in the intestinal mucosa. These interactions may pave the way to the development, growth and spreading of cancer, especially in the gastro-intestinal system. Here, we review the changes in microbiota composition, how they relate to the immunological imbalance, influencing the onset of different types of cancer and the impact of these mechanisms on the efficacy of traditional and upcoming cancer treatments.

Diabetes and frailty are highly prevalent conditions that impact the health status of older adults. Perturbations in protein/amino acid metabolism are associated with both functional impairment and type 2 diabetes mellitus (T2DM). In the present study, we compared the concentrations of a panel of circulating 37 amino acids and derivatives between frail/pre-frail older adults with T2DM and robust non-diabetic controls. Sixty-six functionally impaired older persons aged 70+ with T2DM and 30 age and sex-matched controls were included in the analysis. We applied a partial least squares-discriminant analysis (PLS-DA)-based analytical strategy to characterize the metabotype of study participants. The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 94.1 ± 1.9% for frail/pre-frail persons with T2DM and 100% for control participants. Functionally impaired older persons with T2DM showed higher levels of 3-methyl histidine, alanine, arginine, glutamic acid, ethanolamine sarcosine, and tryptophan. Control participants had higher levels of ornithine and taurine. These findings indicate that a specific profile of amino acids and derivatives characterizes pre-frail/frail older persons with T2DM. The dissection of these pathways may provide novel insights into the metabolic perturbations involved in the disabling cascade in older persons with T2DM.

The development of preventive and therapeutic vaccines has played a crucial role in preventing infections and treating chronic and non-communicable diseases, respectively. For a long time, the influence of sex differences on modifying health and disease has not been addressed in clinical and preclinical studies. The interaction of genetic, epigenetic, and hormonal factors plays a role in the sex-related differences in the epidemiology of diseases, clinical manifestations, and the response to treatment. Moreover, sex is one of the leading factors influencing the gut microbiota composition, which could further explain the different predisposition to diseases in men and women. In the same way, differences between sexes occur also in the immune response to vaccines. This narrative review aims to highlight these differences, focusing on the immune response to vaccines. Comparative data about immune responses, vaccine effectiveness, and side effects are reviewed. Hence, the intricate interplay between sex, immunity, and the gut microbiota will be discussed for its potential role in the response to vaccination. Embracing a sex-oriented perspective in research may improve the efficacy of the immune response and allow the design of tailored vaccine schedules.