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1.
Perinatal factors affecting the gut microbiota - are they preventable?
Zietek, M, Szczuko, M, Celewicz, Z, Kordek, A
Ginekologia polska. 2020;(11):709-713
Abstract
Intestinal microbiota affects many aspects of physiological processes. The type of microbiota in the early stages of life is a critical element conditioning the development of the immune response and food tolerance. Disturbed colonization of the digestive tract resulting from the amount or diversity of bacteria colonies stimulates an inflammatory response that is associated in later life with inflammatory and autoimmune diseases. One of the elements disturbing normal colonization in the perinatal period is the operative way of delivery by caesarean section and the administration of antibiotics, used as a prophylactic measure as well as for therapeutic reasons. Based on the current state of knowledge, there is a lot of evidence demonstrating the long-term adverse effects of these modifying agents for gut microbiota, which should be kept to a minimum as far as possible.
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2.
Vaccine therapy for dysbiosis-related diseases.
Fujimoto, K, Uematsu, S
World journal of gastroenterology. 2020;(21):2758-2767
Abstract
Progress in genomic analysis has resulted in the proposal that the intestinal microbiota is a crucial environmental factor in the development of multifactorial diseases, such as obesity, diabetes, rheumatoid arthritis, and inflammatory bowel diseases represented by Crohn's disease and ulcerative colitis. Dysregulated gut microbiome contributes to the pathogenesis of such disorders; however, there are few effective treatments for controlling only disease-mediating bacteria. Here, we review current knowledge about the intestinal microbiome in health and disease, and discuss a regulatory strategy using a parenteral vaccine with emulsified curdlan and CpG oligodeoxynucleotides, which we have recently developed. Unlike other conventional injectable immunizations, our vaccine contributes to the induction of antigen-specific systemic and mucosal immunity. This vaccine strategy can prevent infectious diseases such as Streptococcus pneumoniae infection, and control metabolic symptoms mediated by intestinal bacteria (e.g. Clostridium ramosum) by induction of high titers of antigen-specific IgA at target mucosal sites. In the future, our vaccination approach could be an effective therapy for common infectious diseases and dysbiosis-related disorders that have been difficult to control so far.
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3.
Importance of the Microbiota Inhibitory Mechanism on the Warburg Effect in Colorectal Cancer Cells.
Eslami, M, Sadrifar, S, Karbalaei, M, Keikha, M, Kobyliak, NM, Yousefi, B
Journal of gastrointestinal cancer. 2020;(3):738-747
Abstract
METHODS AND RESULTS Colorectal cancer (CRC) is the third most common cancer in the world. Genetic backgrounds, lifestyle, and diet play an important role in CRC risk. The human gut microbiota has an influence on many features of human physiology such as metabolism, nutrient absorption, and immune function. Imbalance of the microbiota has been implicated in many disorders including CRC. It seems Warburg effect hypothesis corresponds to the early beginning of carcinogenesis because of eventual failure in the synthesis of a pyruvate dehydrogenase complex in cooperation with a supply of glucose in carbohydrates rich diets. From investigation among previous publications, we attempted to make it clear importance of Warburg effect in tumors; it also discusses the mechanisms of probiotics in inhibiting tumor progression and reverse Warburg effect of probiotics in modulating the microbiota and CRC therapies. These effects were observed in some clinical trials, the application of probiotics as a therapeutic agent against CRC still requirements further investigation. CONCLUSION Fiber is fermented by colonic bacteria into SCFAs such as butyrate/acetate, which may play a vital role in normal homeostasis by promoting turnover of the colonic epithelium. Butyrate enters the nucleus and functions as a histone deacetylase inhibitor (HDACi). Because cancerous colonocytes undertake the Warburg effect pathway, their favored energy source is glucose instead of butyrate. Therefore, accumulation of moderate concentrations of butyrate in cancerous colonocytes and role as HDACi. Probiotics have been shown to play a protective role against cancer development by modulating intestinal microbiota and immune response.
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4.
Gut Microbiota as a Positive Potential Therapeutic Factor in Carcinogenesis: an Overview of Microbiota-Targeted Therapy.
Joukar, F, Mavaddati, S, Mansour-Ghanaei, F, Samadani, AA
Journal of gastrointestinal cancer. 2020;(2):363-378
Abstract
Cancer therapeutic methods comprising chemotherapy, radiotherapy, and surgery are so routine in cancer treatment. Remarkably, there are several personal features which affect the effectiveness of such treatments including nutrition, microbiome diversity, and physical activity which has distinct significant roles during and after therapies along with their bilateral connections. In this way, the ability of gut microbiota36 in modulating the efficacy of chemotherapeutic medications in cancer and other types of disorders is of great importance. In addition, the role of dietary, probiotic, and synthetically engineered bacteria in manipulating and optimizing the gut microbiota is of interest. Conspicuously, the correlation between the commensal microbiota and also host can regulate the physiological activities comprising the immunity system and inflammatory agents and it is scanned in the category of cancers. Bacterial species have been employed in cancer therapy; commensal microbes posse a key beneficial role in this field. Practically, the microbiota has this potential to accelerate and modulates a certain response by priming in order to release the pro-inflammatory agents. We would like to discuss these vital factors in this review as gut microbiota has the potential to be the main option for personalized cancer treatment strategies in the future. Meaning, this novel data present clinical promising feasibilities of modulating cancer therapy with using microbiota.
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5.
Brain-gut-microbiome interactions in obesity and food addiction.
Gupta, A, Osadchiy, V, Mayer, EA
Nature reviews. Gastroenterology & hepatology. 2020;(11):655-672
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Abstract
Normal eating behaviour is coordinated by the tightly regulated balance between intestinal and extra-intestinal homeostatic and hedonic mechanisms. By contrast, food addiction is a complex, maladaptive eating behaviour that reflects alterations in brain-gut-microbiome (BGM) interactions and a shift of this balance towards hedonic mechanisms. Each component of the BGM axis has been implicated in the development of food addiction, with both brain to gut and gut to brain signalling playing a role. Early-life influences can prime the infant gut microbiome and brain for food addiction, which might be further reinforced by increased antibiotic usage and dietary patterns throughout adulthood. The ubiquitous availability and marketing of inexpensive, highly palatable and calorie-dense food can further shift this balance towards hedonic eating through both central (disruptions in dopaminergic signalling) and intestinal (vagal afferent function, metabolic endotoxaemia, systemic immune activation, changes to gut microbiome and metabolome) mechanisms. In this Review, we propose a systems biology model of BGM interactions, which incorporates published reports on food addiction, and provides novel insights into treatment targets aimed at each level of the BGM axis.
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6.
Microbiome and Its Role in Irritable Bowel Syndrome.
Pimentel, M, Lembo, A
Digestive diseases and sciences. 2020;(3):829-839
Abstract
Irritable bowel syndrome (IBS) is an extremely common and often very debilitating chronic functional gastrointestinal disorder. Despite its prevalence, significant associated healthcare costs, and quality-of-life issues for affected individuals, our understanding of its etiology remained limited. However, it is now evident that microbial factors play key roles in IBS pathophysiology. Acute gastroenteritis following exposure to pathogens can precipitate the development of IBS, and studies have demonstrated changes in the gut microbiome in IBS patients. These changes may explain some of the symptoms of IBS, including visceral hypersensitivity, as gut microbes exert effects on the host immune system and gut barrier function, as well as the brain-gut axis. Microbial differences also appear to underlie the two main functional categories of IBS: diarrhea-predominant IBS (IBS-D) is associated with small intestinal bacterial overgrowth, which can be diagnosed by a positive hydrogen breath test, and constipation-predominant IBS (IBS-C) is associated with increased levels of methanogenic archaea, which can be diagnosed by a positive methane breath test. Mechanistically, the pathogens that cause gastroenteritis and trigger subsequent IBS development produce a common toxin, cytolethal distending toxin B (CdtB), and antibodies raised against CdtB cross-react with the cytoskeletal protein vinculin and impair gut motility, facilitating bacterial overgrowth. In contrast, methane gas slows intestinal contractility, which may facilitate the development of constipation. While antibiotics and dietary manipulations have been used to relieve IBS symptoms, with varying success, elucidating the specific mechanisms by which gut microbes exert their effects on the host may allow the development of targeted treatments that may successfully treat the underlying causes of IBS.
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7.
Host-microbiome intestinal interactions during early life: considerations for atopy and asthma development.
Pettersen, VK, Arrieta, MC
Current opinion in allergy and clinical immunology. 2020;(2):138-148
Abstract
PURPOSE OF REVIEW The body's largest microbial community, the gut microbiome, is in contact with mucosal surfaces populated with epithelial, immune, endocrine and nerve cells, all of which sense and respond to microbial signals. These mutual interactions have led to a functional coevolution between the microbes and human physiology. Examples of coadaptation are anaerobes Bifidobacteria and Bacteroides, which have adjusted their metabolism to dietary components of human milk, and infant immune development, which has evolved to become reliant on the presence of beneficial microbes. Current research suggests that specific composition of the early-life gut microbiome aligns with the maturation of host immunity. Disruptions of natural microbial succession patterns during gut colonization are a consistent feature of immune-mediated diseases, including atopy and asthma. RECENT FINDINGS Here, we catalog recent birth cohorts documenting associations between immune dysregulation and microbial alterations, and summarize the evidence supporting the role of the gut microbiome as an etiological determinant of immune-mediated allergic diseases. SUMMARY Ecological concepts that describe microbial dynamics in the context of the host environment, and a portray of immune and neuroendocrine signaling induced by host-microbiome interactions, have become indispensable in describing the molecular role of early-life microbiome in atopy and asthma susceptibility.
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8.
Histone Deacetylase Modifications by Probiotics in Colorectal Cancer.
Salek Farrokhi, A, Mohammadlou, M, Abdollahi, M, Eslami, M, Yousefi, B
Journal of gastrointestinal cancer. 2020;(3):754-764
Abstract
It has been demonstrated that epigenetic modifications of histone (acetylation/deacetylation) participate in a critical role in cancer progression by the regulation of gene expression. Several processes could be regulated by deacetylation of histone and non-histone proteins such as apoptosis, proliferation, cell metabolism, differentiation, and DNA repair. Hence, histone deacetylase inhibitors (HDACis) are employed as a hopeful group of anti-cancer drugs that could inhibit tumor cell proliferation or apoptosis. The elimination of the acetylation marks that take place as an essential epigenetic change in cancer cells is associated to HDAC expression and activity. In this regard, it has been reported that class I HDACs have a vital role in the regulation of tumor cell proliferation. OBJECTIVES In this review, we discuss whether gut origin microorganisms could promote cancer or tumor resistance and explain mechanisms of these processes. CONCLUSIONS According to the enormous capacity of the metabolism of the intestine microbiota, bacteria are likely to convert nutrients and digestive compounds into metabolites that regulate epigenetic in cancer. The effect of the food is of interest on epigenetic changes in the intestinal mucosa and colonocytes, as misleading nucleotide methylation may be a prognostic marker for colorectal cancer (CRC). Since epigenetic changes are potentially reversible, they can serve as therapeutic targets for preventing CRC. However, various mechanisms have been identified in the field of prevention, treatment, and progression of cancer by probiotics, which include intestinal microbiota modulation, increased intestinal barrier function, degradation of potential carcinogens, protective effect on intestinal epithelial damage, and increased immune function.
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Clinical nutrition for the gastroenterologist: the physiologic rationale for providing early nutritional therapy to the hospitalized patient.
McClave, SA, Omer, E
Current opinion in gastroenterology. 2020;(2):118-121
Abstract
PURPOSE OF REVIEW Conflicting reports in the literature have been misinterpreted by clinicians, who conclude that nutritional therapy for the hospitalized patient is of marginal value. The true benefit of such therapy is derived from the provision of early enteral nutrition. This article describes the physiologic response to enteral feeding, which accounts for the outcome benefits, and illustrates how use of the gut alters immune responses and the intestinal microbiota. RECENT FINDINGS The provision of early enteral nutrition has been shown to reduce infection and mortality in high-risk hospitalized patients (compared with not providing such therapy). Early feeding maintains gut integrity, reduces permeability, promotes tolerance and appropriate immune responses, and supports commensalism of the intestinal microbiota. Early enteral nutrition influences cross-talk signaling between luminal bacteria and the intestinal epithelium. Failure to utilize the gut in acute illness can amplify the systemic inflammatory response syndrome and worsen disease severity, while at the same time promoting antibiotic resistance and increased septic morbidity. SUMMARY Appropriate nutritional therapy does change outcomes in the hospitalized patient, especially for those who are at risk on the basis of disease severity and/or poor nutritional status. Greatest benefit is seen from those therapeutic regimens that specifically target gut defenses and the intestinal microbiome.
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10.
Probiotics function and modulation of the immune system in allergic diseases.
Eslami, M, Bahar, A, Keikha, M, Karbalaei, M, Kobyliak, NM, Yousefi, B
Allergologia et immunopathologia. 2020;(6):771-788
Abstract
Allergic diseases have been a global problem over the past few decades. The effect of allergic diseases on healthcare systems and society is generally remarkable and is considered as one of the most common causes of chronic and hospitalized disease. The functional ability of probiotics to modulate the innate/acquired immune system leads to the initiation of mucosal/systemic immune responses. Gut microbiota plays a beneficial role in food digestion, development of the immune system, control/growth of the intestinal epithelial cells and their differentiation. Prescribing probiotics causes a significant change in the intestinal microflora and modulates cytokine secretion, including networks of genes, TLRs, signaling molecules and increased intestinal IgA responses. The modulation of the Th1/Th2 balance is done by probiotics, which suppress Th2 responses with shifts to Th1 and thereby prevent allergies. In general, probiotics are associated with a decrease in inflammation by increasing butyrate production and induction of tolerance with an increase in the ratio of cytokines such as IL-4, IL-10/IFN-γ, Treg/TGF-β, reducing serum eosinophil levels and the expression of metalloproteinase-9 which contribute to the improvement of the allergic disease's symptoms. Finally, it can be said that the therapeutic approach to immunotherapy and the reduction of the risk of side effects in the treatment of allergic diseases is the first priority of treatment and the final approach that completes the first priority in maintaining the condition and sustainability of the tolerance along with the recovery of the individual.