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Background: The gut barrier is a sophisticated and dynamic system that forms the frontline defense between the external environment and the body's internal milieu and includes various structural and functional components engaged not only in digestion and nutrient absorption but also in immune regulation and overall health maintenance., Summary: When one or more components of the intestinal barrier lose their structure and escape their function, this may result in a leaky gut. Mounting evidence emphasizes the crucial role of the gut microbiome in preserving the integrity of the gut barrier and provides insights into the pathophysiological implications of conditions related to leaky gut in humans. Assessment of intestinal permeability has evolved from invasive techniques to noninvasive biomarkers, but challenges remain in achieving consensus about the best testing methods and their accuracy. Research on the modulation of gut permeability is just starting, and although no medical guidelines for the treatment of leaky gut syndrome are available, several treatment strategies are under investigation with promising results., Key Messages: This review discusses the composition of the intestinal barrier, the pathophysiology of the leaky gut and its implications on human health, the measurement of intestinal permeability, and the therapeutic strategies to restore gut barrier integrity., (© 2024 S. Karger AG, Basel.)

Background: Multiple lines of evidence now support the notion that gut microbiota can contribute to digestive and extra-digestive diseases. The emergence of these observations enabled to postulate a bacteria-centric paradigm to rethink the treatment of many diseases. The goal of therapy should not be to eradicate the flora but to modify it in a way that leads to symptomatic improvement; thus, the interest in the use of probiotics to modulate microbiota composition has increased worldwide in both community and healthcare settings., Summary: The results of published studies are conflicting for most probiotic strains and formulations, and clinicians and consumers need a better understanding of probiotic risks and benefits. Currently, clear guidelines on when to use probiotics and the most effective probiotic for different gastrointestinal conditions are still lacking. Here, we reviewed the studies on the use of probiotics in some diseases of relevant interest to gastroenterologists, such as Helicobacter pylori infection, irritable bowel syndrome, and inflammatory bowel disease. Key Message: Although the evidence is relevant and promising for probiotics in general, and for specific strains and combinations of strains, it is not yet sufficient to draw unequivocal conclusions and clear recommendations., (© 2021 S. Karger AG, Basel.)

It is now well established that a healthy gut flora is largely responsible for the overall health of the host, while a perturbation in gut microbial communities can contribute to disease susceptibility. Obesity is a complex process involving genetic and environmental factors with an epidemiological burden that makes it a major public health issue. Studies of germ-free or gnotobiotic mice provided evidence that the diversity, as well as the presence and relative proportion of different microbes in the gut play active roles in energy homeostasis. Similarly, human studies showed that both the diversity of the microbiota and the Bacteroidetes/Firmicutes ratio are decreased in obese individuals. The 'obese microbiota' seems to be able to increase dietary energy harvest and favor weight gain and fat deposition. Although research in this field has just started and many of the available data are still conflicting, the results are providing exciting perspectives, and gut microbiota manipulation has already become a new target for both prevention and treatment of obesity., (© 2016 S. Karger AG, Basel.)

Although the idea that gastric problems are in some way related to mental activity dates back to the beginning of the last century, until now it has received scant attention by physiologists, general practitioners and gastroenterologists. The major breakthrough in understanding the interactions between the central nervous system and the gut was the discovery of the enteric nervous system (ENS) in the 19th century. ENS (also called 'little brain') plays a crucial role in the regulation of the physiological gut functions. Furthermore, the identification of corticotropin-releasing factor (CRF) and the development of specific CRF receptor antagonists have permitted to characterize the neurochemical basis of the stress response. The neurobiological response to stress in mammals involves three key mechanisms: (1) stress is perceived and processed by higher brain centers; (2) the brain mounts a neuroendocrine response by way of the hypothalamic-pituitary-adrenal axis (HPA) and the autonomic nervous system (ANS), and (3) the brain triggers feedback mechanisms by HPA and ANS stimulation to restore homeostasis. Various stressors such as anger, fear, painful stimuli, as well as life or social learning experiences affect both the individual's physiologic and gastric function, revealing a two-way interaction between brain and stomach. There is overwhelming experimental and clinical evidence that stress influences gastric function, thereby outlining the pathogenesis of gastric diseases such as functional dyspepsia, gastroesophageal reflux disease and peptic ulcer disease. A better understanding of the role of pathological stressors in the modulation of disease activity may have important pathogenetic and therapeutic implications., (© 2014 S. Karger AG, Basel.)

It is estimated that 20% of malignancies worldwide can be attributed to infections, i.e. about 1.2 million cases per year. A typical example of the association between bacterial infection and gastrointestinal malignancies is Helicobacter pylori infection with both gastric cancer and mucosa-associated lymphoid tissue lymphoma. Bacteria are an important component of the human body. The human intestine contains >500 different types of microorganisms, the 'gut microbiota', that play important functions such as energetic metabolism, proliferation and survival of epithelial cells, and protection against pathogens. Chronic alteration of intestinal microbiota homeostasis, 'dysbiosis', could promote many diseases, including cancer. The mechanisms by which bacteria may induce carcinogenesis include chronic inflammation, immune evasion, and immune suppression. There are three effector pathways of T helper (Th) cell differentiation: Th1 responses promoted by procarcinogenic signal transducer and activator of transcription (Stat)1 and Stat4 signaling, Th2 responses promoted by Stat6 signaling, and Th17 responses promoted by Stat3 signaling. Interestingly, Th1 responses, driven by IL-12 and characterized by IFN-γ production, are typically anticarcinogenic, whereas Th17 responses are activated in various cancers. Furthermore, a T regulatory response, driven by IL-10 and TGF-β, counterbalances the proinflammatory effect of Th17 responses. Elevated numbers of T regulatory cells suppress the innate and adaptive immune responses, thereby contributing to tumor progression. The emerging relationship between gut microbiota and cancer has prompted new ways of thinking about cancer prevention and has led to the development of noninvasive diagnostic tests and innovative treatments, such as with probiotics. However, although in vitro and animal model studies suggest a protective anticancer effect of probiotics, the results of human epidemiological studies are controversial., (Copyright © 2011 S. Karger AG, Basel.)

Gastric carcinogenesis is a multistep process triggered by Helicobacter pylori and characterized by accumulation of molecular alterations. Two mechanisms are implicated in cancer-related molecular alterations: genetic and epigenetic. The former includes changes in the DNA sequence, the latter occurs without changes of DNA sequence. However, the most important difference between genetic and epigenetic alterations is that epigenetic changes are potentially reversible by eliminating toxic agents. DNA methylation is the major epigenetic phenomenon of eukaryotic genomes and involves the addition of a methyl group to the carbon 5 position of the cytosine ring within the CpG dinucleotide. DNA methylation is needed for the normal development of cells, whereas aberrant methylation of CpG islands confers a selective growth advantage that results in cancerous growth. The stomach is one of the organs frequently showing aberrant methylation of DNA epithelial cells because of its accessibility to exogenous toxic agents such as H. pylori infection. Aberrant methylation of CpG islands occurs early in gastric carcinogenesis, tends to increase as the process advances and is prevalently related to the infection. In conclusion, gastric cancer is mainly an epigenetic disease and H. pylori, acting through inflammatory mediators, may play a key role in the development of such molecular alterations., (2007 S. Karger AG, Basel)

Gastric cancer remains a leading cause of cancer-related deaths in many parts of the world. At present, prevention seems to be the most effective means to reduce its the incidence and mortality rate. Gastric atrophy is considered the first relevant step in the histogenesis of gastric adenocarcinoma. However, whether screening for and surveillance of atrophic gastritis is advisable is debated. The prevalence and pattern of chronic atrophic gastritis varies greatly from country to country, being higher and mainly diffuse pangastritis or localized in those countries with a high gastric cancer incidence. The only method available to detect gastric atrophy is histopathological examination of endoscopic specimens, but there is no consensus about diagnosis. Serum gastric secretion may be a marker of gastric atrophy, although it has high specificity but low sensitivity. Gastric atrophy is mainly related to chronic Helicobacter pylori (H. pylori) infection. Thus, the only effective strategy for gastric cancer prevention is eradication of H. pylori infection to arrest atrophy progression in selected populations. In conclusion, there is insufficient evidence to suggest screening for and surveillance of atrophic gastritis in the general population; however, this strategy should be applied in countries with a high incidence of gastric cancer., (2007 S. Karger AG, Basel)