1,721,050 research outputs found
The role of gut microbiota in the pathogenesis and management of allergic diseases.
No full textAllergy is defined as a hypersensitivity reaction due to specific antibody-mediated or cell-mediated immunologic mechanisms. Epidemiological studies are showing a dramatic increase of allergies in industrialized countries in the last few decades, while remaining stable in developing countries. In 1989 Strachan, hypothesized that the increase in allergic disorders was the result of a lack of infections in early infancy, and in 1998 Wold suggested that, rather than a decrease in viral or bacterial infections, an altered normal intestinal colonization pattern in infancy, could be responsible for the increase in allergies. Germ-free mice were shown to mount an exaggerated allergic airway reaction compared with that seen in colonized mice, indicating the important role of microbe-host interactions in the development of allergic diseases. Infants with food allergies are found to exhibit an imbalance between "beneficial"and potentially harmful bacteria, i.e., decreased Lactobacilli, Bifidobacteria and Enterococcus species and increased coliforms, Staphylococcus aureus and Clostridium species, suggesting that microbial inhabitants of the human body, may play either a pathogenic or protective role in allergies. Based on this data, many clinical trial addressing the use of probiotics in the context of allergic disorders, have been conducted in children. However, currently, no conclusive item may be drawn
The bacteria hypothesis of colorectal cancer: pathogenetic and therapeutic implications
No full textIt is estimated that up to 20% of malignancies worldwide can be attributed to infections. The most convincing evidence, in this context, is the link between Helicobacter pylori and both gastric cancer and mucosa-associated lymphoid tissue (MALT) lymphoma. A growing body of evidence in the last years has raised up the question of the putative causal role of gut microbiota in the carcinogenetic process. Bacteria are an important component of the human body. The human intestine contains >500 different types of microorganisms, usually referred to as the commensal intestinal microbiota. A chronic alteration of the intestinal microbiota homeostasis or dysbiosis” underlies many diseases, including cancer. The main mechanisms by which bacteria may induce carcinogenesis include chronic inflammation, immune evasion
and immune suppression. If the microbiota is involved in cancer development, being the colon the site where the microbiota reaches its highest concentration, it is expected to be its major site of action. Numerous data from experimental,
animal model and human studies support the gut-bacteria hypothesis of colorectal cancer (CRC). Germ-free rats, compared with conventionally reared animals, develop fewer and smaller tumors both spontaneously and after chemically-induced CRC. The absence of the physiological inflammation caused by the commensal microbiota may explain the capability of the germ-free rats to develop a more efficacious anti-cancer immune response. Several microorganisms, including Streptococcus bovis, Bacteroides fragilis and Escherichia coli have been implicated in the pathogenesis of CRC. The emerging relationship between gut microbiota and cancer prompts new ways of thinking about cancer prevention and leads to the development of innovative treatments such as probiotics. However, although in vitro and animal model studies suggest a protective anticancer effect of probiotics, the results of human epidemiological studies are still controversial and very few data are available from interventional studies
The Psyche and Gastric Functions
No full textAlthough 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 implication
Contribution of gut microbiota to colonic and extracolonic cancer development.
No full textIt 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
The human gastric microbiota: Is it time to rethink the pathogenesis of stomach diseases?
No full textNTRODUCTION:
Although long thought to be a sterile organ, due to its acid production, the human stomach holds a core microbiome.
AIM:
To provide an update of findings related to gastric microbiota and its link with gastric diseases.
METHODS:
We conducted a systematic review of the literature.
RESULTS:
The development of culture-independent methods facilitated the identification of many bacteria. Five major phyla have been detected in the stomach: Firmicutes, Bacteroidites, Actinobacteria, Fusobacteria and Proteobacteria. At the genera level, the healthy human stomach is dominated by Prevotella, Streptococcus, Veillonella, Rothia and Haemophilus; however, the composition of the gastric microbiota is dynamic and affected by such factors as diet, drugs and diseases. The interaction between the pre-existing gastric microbiota and Helicobacter pylori infection might influence an individual's risk of gastric disease, including gastric cancer.
CONCLUSIONS:
The maintenance of bacterial homeostasis could be essential for the stomach's health and highlights the chance for therapeutic interventions targeting the gastric microbiota, even if gastric pH, peristalsis and the mucus layer may prevent bacteria colonization; and the definition of gastric microbiota of the healthy stomach is still an ongoing challenging task
Epigenetic alterations due to diet and Helicobacter pylori infection in gastric carcinogenesis
No full textSporadic gastric cancer is considered to be the result of a progressive accumulation of genotypic changes due to an adverse environment (i.e., diet and Helicobacter pylori infection). The main molecular mechanism implicated in cancer-related molecular alterations is of epigenetic nature, which includes DNA methylation and histone modification. Diet may influence the methylation status supplying methyl groups S-adenosyl-methionine formation, modifying DNA methyltransferase activity and influencing DNA demethylation activity. H. pylori may affect DNA methyltransferase directly or through inflammatory mediators (e.g., reactive oxygen species or nitric oxide). In conclusion, gastric cancer is a multistep process due to an adverse environment over a long period of time. Dietary habit and H. pylori infection can induce epigenetic alterations that, in turn, trigger gastric carcinogenesis
Screening for and surveillance of gastric cancer
No full textAlthough the prevalence of gastric cancer (GC) progressively decreased during the last decades, due to improved dietary habit, introduction of food refrigeration and recovered socio-economic level, it still accounts for 10% of the total cancer-related deaths. The best strategy to reduce the mortality for GC is to schedule appropriate screening and surveillance programs, that rises many relevant concerns taking into account its worldwide variability, natural history, diagnostic tools, therapeutic strategies, and cost-effectiveness. Intestinal-type, the most frequent GC histotype, develops through a multistep process triggered by Helicobacter pylori (H. pylori) and progressing from gastritis to atrophy, intestinal metaplasia (IM), and dysplasia. However, the majority of patients infected with H. pylori and carrying premalignant lesions do not develop GC. Therefore, it remains unclear who should be screened, when the screening should be started and how the screening should be performed. It seems reasonable that screening programs should target the general population in eastern countries, at high prevalence of GC and the high-risk subjects in western countries, at low prevalence of GC. As far as concern surveillance, currently, we are lacking of standardized international recommendations and many features have to be defined regarding the optimal diagnostic approach, the patients at higher risk, the best timing and the cost-effectiveness. Anyway, patients with corpus atrophic gastritis, extensive incomplete IM and dysplasia should enter a surveillance program. At present, screening and surveillance programs need further studies to draw worldwide reliable recommendations and evaluate the impact on mortality for GC
Cancer stem cell hypothesis and gastric carcinogenesis: Experimental evidence and unsolved questions
No full textTraditionally, the clonal evolution model has been used to explain gastric cancer (GC) growth dynamics. According to this model, GC cells result from multiple mutations over time resulting in a population of continually diversifying cells. This heterogeneity enables the survival of different clones under particular conditions allowing growth at metastatic locations or resistance to chemotherapeutics. Cancer stem cell (CSC) theory completely overturns this traditional understanding of cancer suggesting that only CSCs can self-renew and promote tumor growth. CSCs are relatively refractory to conventional therapies, thus explaining why anti-cancer therapies are far from curative and why relapses of cancer are frequent. The identification of the CSC component of a tumor might, thus, open new therapeutic perspective based on the selective targeting of this small population of cells. In this review we examine the current scientific evidence supporting the existence of CSC in gastric tumors and analyze the main unsolved questions of this difficult field of cancer research
Reply to: "Prediction of liver fibrosis progression by non-invasive tests in chronic hepatitis C: the impact of validation".
No full textRisk factors in gastric cancer
Full text linkSTATE OF THE ART: Gastric cancer (GC) is still a major health problem worldwide due to its frequency, poor prognosis and limited treatment options. At present prevention is likely to be the most effective means of reducing the incidence and mortality from this disease. The most important etiological factors implicated in gastric carcinogenesis are diet and Helicobacter pylori (H. pylori) infection. High intake of salted, pickled or smoked foods, as well as dried fish and meat and refined carbohydrates significantly increased the risk of developing GC while fibers, fresh vegetables and fruit were found to be inversely associated with GC risk. Epidemiological investigations (retrospective, case-control and prospective) and several meta-analyses have demonstrated that concurrent or previous H. pylori infection is associated with an increased risk of GC in respect to uninfected people. H. pylori colonizes gastric mucosa where it induces a complex inflammatory and immune reaction that on time leads to a severe mucosal damage i.e., atrophy, intestinal metaplasia (IM) and dysplasia. The risk of GC is closely related to the grade and extension of gastric atrophy, IM and dysplasia. PERSPECTIVES AND CONCLUSIONS: Today a plausible program for GC prevention means: (1) a correct dietary habit since childhood increasing vegetables and fruit intake, (2) a decrease of H. pylori spread improving family and community sanitation and hygiene, (3) a search and treat H. pylori strategy in offspring of GC, (4) a search and treat H. pylori strategy in patients with chronic atrophic gastritis and intestinal metaplasia (IM), (5) a careful endoscopic and histologic follow-up if precancerous lesions persist irrespective of H. pylori eradication
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