In recent years, gender medicine has emerged as a field of research analyzing sex-related differences in health and disease. Biological sex, depending on sex chromosome complement, sex steroid hormones, and reproductive organs, has been demonstrated to influence human susceptibility to infections, immune responses against pathogens, the clinical severity of infectious diseases, and responses to the available treatments. Men and women differ in their chromosome set, with men having one X chromosome (XY) and women two (XX). This different genetic composition results in a sex-dimorphic expression of genes and pathways involved in immune regulation, as well as in shaping immune responses to infectious agents. Moreover, estrogen, progesterone, and testosterone, impacting cells and pathways involved in both innate and adaptive immunity, have been shown to drive sex dimorphism in infectious diseases. This narrative review aims to explore the sex-related differences in responses to infections, specifically focusing on the underlying genetic and hormonal mechanisms. Hence, aging-related changes in the immune system and their potential impact on immune responses against pathogens will be discussed. Understanding sex differences and stratifying the population according to them will open the door to precision medicine and personalized patient care.

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.

The term ‘inflammaging’ has been coined to describe the chronic state of inflammation derived from ongoing cycles of tissue damage and the subsequent immune responses. This inflammatory status contributes to the decline of organs and physiological functions, accelerates the aging process, and increases the risk of age-related illnesses and death. During aging, the gut microbiota (GM) undergoes significant changes, including a decreased diversity of species, a decline in beneficial bacteria, and a rise in proinflammatory ones, resulting in persistent low-grade inflammation. Moreover, environmental factors, such as diet and medications, contribute to age-related changes in GM and immune function, preventing or promoting inflammaging. This narrative review aims to clarify the underlying mechanisms of inflammaging and to specifically investigate the influence of GM and several environmental factors on these mechanisms, while also exploring potential differences related to sex. Moreover, lifestyle and pharmacological interventions will be suggested to promote healthy aging.

In recent years, there has been a growing interest in the concept of the “gut–brain axis”. In addition to well-studied diseases associated with an imbalance in gut microbiota, such as cancer, chronic inflammation, and cardiovascular diseases, research is now exploring the potential role of gut microbial dysbiosis in the onset and development of brain-related diseases. When the function of the intestinal barrier is altered by dysbiosis, the aberrant immune system response interacts with the nervous system, leading to a state of “neuroinflammation”. The gut microbiota–brain axis is mediated by inflammatory and immunological mechanisms, neurotransmitters, and neuroendocrine pathways. This narrative review aims to illustrate the molecular basis of neuroinflammation and elaborate on the concept of the gut–brain axis by virtue of analyzing the various metabolites produced by the gut microbiome and how they might impact the nervous system. Additionally, the current review will highlight how sex influences these molecular mechanisms. In fact, sex hormones impact the brain–gut microbiota axis at different levels, such as the central nervous system, the enteric nervous one, and enteroendocrine cells. A deeper understanding of the gut–brain axis in human health and disease is crucial to guide diagnoses, treatments, and preventive interventions.

According to the definition provided by the United Nations, “climate change” describes the persistent alterations in temperatures and weather trends. These alterations may arise naturally, such as fluctuations in the solar cycle. Nonetheless, since the 19th century, human activities have emerged as the primary agent for climate change, primarily attributed to the combustion of fossil fuels such as coal, oil, and gas. Climate change can potentially influence the well-being, agricultural production, housing, safety, and employment opportunities for all individuals. The immune system is an important interface through which global climate change affects human health. Extreme heat, weather events and environmental pollutants could impair both innate and adaptive immune responses, promoting inflammation and genomic instability, and increasing the risk of autoimmune and chronic inflammatory diseases. Moreover, climate change has an impact on both soil and gut microbiome composition, which can further explain changes in human health outcomes. This narrative review aims to explore the influence of climate change on human health and disease, focusing specifically on its effects on the immune system and gut microbiota. Understanding how these factors contribute to the development of physical and mental illness may allow for the design of strategies aimed at reducing the negative impact of climate and pollution on human health.

The exposome encompasses all endogenous and exogenous exposure individuals encounter throughout their lives, including biological, chemical, physical, psychological, relational, and socioeconomic factors. It examines the duration and intensity of these types of exposure and their complex interactions over time. This interdisciplinary approach involves various scientific disciplines, particularly toxicology, to understand the long-term effects of toxic exposure on health. Factors like air pollution, racial background, and socioeconomic status significantly contribute to diseases such as metabolic, cardiovascular, neurodegenerative diseases, infertility, and cancer. Advanced analytical methods measure contaminants in biofluids, food, air, water, and soil, but often overlook the cumulative risk of multiple chemicals. An exposome analysis necessitates sophisticated tools and methodologies to understand health interactions and integrate findings into precision medicine for better disease diagnosis and treatment. Chronic exposure to environmental and biological stimuli can lead to persistent low-grade inflammation, which is a key factor in chronic non-communicable diseases (NCDs), such as obesity, cardiometabolic disorders, cancer, respiratory diseases, autoimmune conditions, and depression. These NCDs are influenced by smoking, unhealthy diets, physical inactivity, and alcohol abuse, all shaped by genetic, environmental, and social factors. Dietary patterns, especially ultra-processed foods, can exacerbate inflammation and alter gut microbiota. This study investigates the exposome’s role in the prevention, development, and progression of NCDs, focusing on endogenous and exogenous factors.