Body Composition and Alzheimer's Disease: A Holistic Review.

Alzheimer's disease (AD) represents a significant global health challenge and affects approximately 50 million people worldwide. This overview of published reviews provides a comprehensive understanding of the intricate correlations between AD and body composition, focusing particularly on obesity. We used a systematic approach to collect and analyze relevant reviews on the topic of obesity and Alzheimer's disease. A comprehensive search of electronic databases, including PubMed, MEDLINE, and Google Scholar, was conducted. We searched keywords such as "Alzheimer's disease", "body composition", "lean mass", "bone mass", and "fat mass". We considered only reviews written within the past 5 years and in English. Fifty-six relevant reviews were identified that shed light on the multiple connections between AD and body composition. The review involves several aspects, including the impact of lean mass, bone mass, and endocrinological factors related to obesity, as well as inflammation, neuroinflammation, and molecular/genetic factors. The findings highlight the complex interplay of these elements in the development of AD, underscoring the need for holistic approaches to reduce the risk of AD and to explore innovative strategies for diagnosis, prevention, and treatment.

Sex Differences in Cardiovascular Diseases: Exploring the Role of Microbiota and Immunity.

Cardiovascular diseases (CVDs) are the most common cause of mortality and morbidity in Western countries, thus representing a global health concern. CVDs show different patterns in terms of the prevalence and presentation in men and women. The role of sex hormones has been extensively implicated in these sex-specific differences, due to the presence of the menstrual cycle and menopause in women. Moreover, the gut microbiota (GM) has been implicated in cardiovascular health, considering the growing evidence that it is involved in determining the development of specific diseases. In particular, gut-derived metabolites have been linked to CVDs and kidney disorders, which can in turn promote the progression of CVDs. Considering the differences in the composition of GM between men and women, it is possible that gut microbiota act as a mediator in regard to the sex disparities in CVDs. This narrative review aims to comprehensively review the interplay between sex, GM, and CVDs, discussing potential mechanisms and therapeutic options.

Inflammaging: The Next Challenge-Exploring the Role of Gut Microbiota, Environmental Factors, and Sex Differences.

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.

Exploring the Exposome Spectrum: Unveiling Endogenous and Exogenous Factors in Non-Communicable Chronic Diseases.

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.

The Impact of Climate Change on Immunity and Gut Microbiota in the Development of Disease.

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.

Gut-Brain Axis: Focus on Sex Differences in Neuroinflammation.

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.

Immune Cells, Gut Microbiota, and Vaccines: A Gender Perspective.

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.

Gut-Kidney-Heart: A Novel Trilogy.

The microbiota represents a key factor in determining health and disease. Its role in inflammation and immunological disorders is well known, but it is also involved in several complex conditions, ranging from neurological to psychiatric, from gastrointestinal to cardiovascular diseases. It has recently been hypothesized that the gut microbiota may act as an intermediary in the close interaction between kidneys and the cardiovascular system, leading to the conceptualization of the "gut-kidney-heart" axis. In this narrative review, we will discuss the impact of the gut microbiota on each system while also reviewing the available data regarding the axis itself. We will also describe the role of gut metabolites in this complex interplay, as well as potential therapeutical perspectives.

Factors Influencing Microbiota in Modulating Vaccine Immune Response: A Long Way to Go.

Vaccine immunogenicity still represents an unmet need in specific populations, such as people from developing countries and "edge populations". Both intrinsic and extrinsic factors, such as the environment, age, and dietary habits, influence cellular and humoral immune responses. The human microbiota represents a potential key to understanding how these factors impact the immune response to vaccination, with its modulation being a potential step to address vaccine immunogenicity. The aim of this narrative review is to explore the intricate interactions between the microbiota and the immune system in response to vaccines, highlighting the state of the art in gut microbiota modulation as a novel therapeutic approach to enhancing vaccine immunogenicity and laying the foundation for future, more solid data for its translation to the clinical practice.

Current Evidence on Vaccinations in Pediatric and Adult Patients with Systemic Autoinflammatory Diseases.

Systemic autoinflammatory diseases (SAIDs) are defined by recurrent febrile attacks associated with protean manifestations involving joints, the gastrointestinal tract, skin, and the central nervous system, combined with elevated inflammatory markers, and are caused by a dysregulation of the innate immune system. From a clinical standpoint, the most known SAIDs are familial Mediterranean fever (FMF); cryopyrin-associated periodic syndrome (CAPS); mevalonate kinase deficiency (MKD); and periodic fever, aphthosis, pharyngitis, and adenitis (PFAPA) syndrome. Current guidelines recommend the regular sequential administration of vaccines for all individuals with SAIDs. However, these patients have a much lower vaccination coverage rates in 'real-world' epidemiological studies than the general population. The main purpose of this review was to evaluate the scientific evidence available on both the efficacy and safety of vaccines in patients with SAIDs. From this analysis, neither serious adverse effects nor poorer antibody responses have been observed after vaccination in patients with SAIDs on treatment with biologic agents. More specifically, no new-onset immune-mediated complications have been observed following immunizations. Post-vaccination acute flares were significantly less frequent in FMF patients treated with colchicine alone than in those treated with both colchicine and canakinumab. Conversely, a decreased risk of SARS-CoV-2 infection has been proved for patients with FMF after vaccination with the mRNA-based BNT162b2 vaccine. Canakinumab did not appear to affect the ability to produce antibodies against non-live vaccines in patients with CAPS, especially if administered with a time lag from the vaccination. On the other hand, our analysis has shown that immunization against Streptococcus pneumoniae, specifically with the pneumococcal polysaccharide vaccine, was associated with a higher incidence of adverse reactions in CAPS patients. In addition, disease flares might be elicited by vaccinations in children with MKD, though no adverse events have been noted despite concurrent treatment with either anakinra or canakinumab. PFAPA patients seem to be less responsive to measles, mumps, and rubella-vaccine, but have shown higher antibody response than healthy controls following vaccination against hepatitis A. In consideration of the clinical frailty of both children and adults with SAIDs, all vaccinations remain 'highly' recommended in this category of patients despite the paucity of data available.

Hematological Complications in a COVID-19 Patient: A Case Report.

Hemophilia A is a hemorrhagic disorder caused by insufficient or inadequate coagulation factor VIII activity. Two different forms are described: congenital, hereditary X-linked, and acquired. Acquired hemophilia A (AHA) is a rare condition and it is defined by the production of autoantibodies neutralizing factor VIII, known as inhibitors. We report the case of a 72-year-old man with a clinical diagnosis of AHA after SARS-CoV-2 infection, which has been described in association with several hematological complications. SARS-CoV-2 infection could represent the immunological trigger for the development of autoantibodies. In our patient, SARS-CoV-2 infection preceded the hemorrhagic complications by 15 days. This lag time is in line with the other cases reported and compatible with the development of an intense immune response with autoantibody production. It is possible that since our patient was affected by type 1 diabetes mellitus, he was more prone to an immune system pathological response against self-antigens. A prompt, appropriate therapeutic intervention with activated recombinant factor VII administration and cyclophosphamide has led to rapid remission of clinical and laboratory findings.