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.

Pollutants, microbiota and immune system: frenemies within the gut.

Pollution is a critical concern of modern society for its heterogeneous effects on human health, despite a widespread lack of awareness. Environmental pollutants promote several pathologies through different molecular mechanisms. Pollutants can affect the immune system and related pathways, perturbing its regulation and triggering pro-inflammatory responses. The exposure to several pollutants also leads to alterations in gut microbiota with a decreasing abundance of beneficial microbes, such as short-chain fatty acid-producing bacteria, and an overgrowth of pro-inflammatory species. The subsequent intestinal barrier dysfunction, together with oxidative stress and increased inflammatory responses, plays a role in the pathogenesis of gastrointestinal inflammatory diseases. Moreover, pollutants encourage the inflammation-dysplasia-carcinoma sequence through various mechanisms, such as oxidative stress, dysregulation of cellular signalling pathways, cell cycle impairment and genomic instability. In this narrative review, we will describe the interplay between pollutants, gut microbiota, and the immune system, focusing on their relationship with inflammatory bowel diseases and colorectal cancer. Understanding the biological mechanisms underlying the health-to-disease transition may allow the design of public health policies aimed at reducing the burden of disease related to pollutants.

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.

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.

Gut Microbiota, Inflammatory Bowel Disease, and Cancer: The Role of Guardians of Innate Immunity.

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.

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.

Effect of COVID-19 Vaccination on the In-Hospital Prognosis of Patients Admitted during Delta and Omicron Waves in Italy.

All-cause mortality related to the SARS-CoV-2 infection has declined from the first wave to subsequent waves, probably through vaccination programs and the availability of effective antiviral therapies. Our study aimed to evaluate the impact of the SARS-CoV-2 vaccination on the prognosis of infected patients. Overall, we enrolled 545 subjects during the Delta variant wave and 276 ones during the Omicron variant wave. Data were collected concerning vaccination status, clinical parameters, comorbidities, lung involvement, laboratory parameters, and pharmacological treatment. Outcomes were admission to the intensive care unit (ICU) and 30-day all-cause mortality. Overall, the final sample included 821 patients with a mean age of 62 ± 18 years [range 18-100], and 59% were men. Vaccinated patients during the Delta wave were 37% (over ¾ with two doses), while during the Omicron wave they were 57%. Vaccinated patients were older (68 vs. 57 years), and 62% had at least one comorbidity Admission to the ICU was 20%, and the mortality rate at 30 days was 14%. ICU admissions were significantly higher during the Delta wave than during Omicron (OR 1.9, 95% CI 1.2-3.1), while all-cause mortality did not differ. Unvaccinated patients had a higher risk of ICU admission (OR 2.0, 95% CI 1.3-3.1) and 30-day all-cause mortality (OR 1.7, 95% CI 1.3-2.7). Results were consistent for both Delta and Omicron variants. Overall, vaccination with at least two doses was associated with a reduced need for ICU admission. Even one shot of the vaccine was associated with a significantly reduced 30-day mortality.

Vaccines, Microbiota and Immunonutrition: Food for Thought.

Vaccines are among the most effective health measures and have contributed to eradicating some diseases. Despite being very effective, response rates are low in some individuals. Different factors have been proposed to explain why some people are not as responsive as others, but what appears to be of critical importance is the presence of a healthy functioning immune system. In this respect, a key factor in modulating the immune system, both in its adaptive and innate components, is the microbiota. While microbiota can be modulated in different ways (i.e., antibiotics, probiotics, prebiotics), an effective and somewhat obvious mechanism is via nutrition. The science of nutrients and their therapeutic application is called immunonutrition, and it is increasingly being considered in several conditions. Our review will focus on the importance of nutrition and microbiota modulation in promoting a healthy immune system while also discussing the overall impact on vaccination response.