The link "Cancer and autoimmune diseases" in the light of microbiota: Evidence of a potential culprit (original) (raw)
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The Challenging Triad: Microbiota, Immune System and Anticancer Drugs
Anti-cancer Drugs - Nature, Synthesis and Cell, 2016
Gut microbiota is essential for the development of the intestinal immune system, protecting the host against pathogens and harmful inflammatory processes. Germ-free animals have smaller Peyer's patches, fewer immune cells and impaired immunoglobulin A (IgA) secretion, fewer intraepithelial lymphocytes, as well as compromised production of antimicrobial peptides. Mucositis (mucosal barrier injury) is a major oncological problem caused by chemotherapeutic agents. Intestinal mucositis translates into a broad spectra of clinical symptoms (diarrhea, vomiting) and can be worsened by neutropenia and antibiotics. Since IECs do not regulate intestinal homeostasis by themselves, but require symbiotic coordination with commensal bacteria and local gut leukocytic cells, the role of intestinal microbiota in the development and severity of mucositis induced by chemotherapeutic products became an issue. The present chapter reviews the interplay between microbiota, immune system, and anticancer therapy. The published researches in this field showed that microbiota has immunomodulatory effect on the anticancer immune response, both in the presence and in the absence of chemotherapy. Animal and human studies evoked that the anticancer response depends on microbiota variability.
Infection, immunoregulation, and cancer
As man has moved rapidly from the hunter-gatherer environment to the living conditions of the industrialized countries, the incidences of some cancers have increased alarmingly. Recent increases are usually attributed to dietary changes or to altered exposures to putative carcinogens associated with the modern lifestyle. However, the changes in cancer incidence parallel similar increases in non-neoplastic chronic inflammatory disorders (inflammatory bowel disease, allergies, and autoimmunity), and the epidemiology is often strikingly similar. This parallel is worth exploring, because the increases in chronic inflammatory disorders are at least partly explained by immunoregulatory defects resulting from diminished exposure to microorganisms that co-evolved with mammals and developed a role in driving immunoregulatory circuits (the hygiene hypothesis). Dysregulated chronic inflammation can drive oncogenesis and also provides growth and angiogenic factors that enhance the subsequent proliferation and spread of tumor cells. Thus, a modern failure to downregulate inappropriate inflammation could underlie increases in some cancers in parallel with the increases in chronic inflammatory disorders. This possibility is supported by recent work showing that in some circumstances regulatory T cells protect against cancer, rather than aggravating it, as previously assumed. A greater understanding of these interactions might pave the way to improved microbe-based immunotherapies.
The interplay between the microbiome and the adaptive immune response in cancer development
Therapeutic Advances in Gastroenterology, 2016
The data from different studies suggest a bacterial role in cancer genesis/progression, often modulating the local immune response. This is particularly so at the mucosal level where the bacterial presence is strong and the immune system is highly reactive. The epithelial surfaces of the body, such as the skin and mucosa, are colonized by a vast number of microorganisms, which represent the so-called normal microbiome. Normally the microbiome does not cause a proinflammatory response because the immune system has developed different strategies for the tolerance of commensal bacteria, but when these mechanisms are impaired or new pathogenic bacteria are introduced into this balanced system, the immune system reacts to the microbiome and can trigger tumor growth in the intestine. In this review, we discuss the potential role of the bacterial microbiome in carcinogenesis, focusing on the direct and indirect immune adaptive mechanisms, that the bacteria can modulate in different ways.
Frontiers in Immunology
The microbiota consists of a dynamic multispecies community of bacteria, fungi, archaea, and protozoans, bringing to the host organism a dowry of cells and genes more numerous than its own. Among the different non-sterile cavities, the human gut harbors the most complex microbiota, with a strong impact on host homeostasis and immunostasis, being thus essential for maintaining the health condition. In this review, we outline the roles of gut microbiota in immunity, starting with the background information supporting the further presentation of the implications of gut microbiota dysbiosis in host susceptibility to infections, hypersensitivity reactions, autoimmunity, chronic inflammation, and cancer. The role of diet and antibiotics in the occurrence of dysbiosis and its pathological consequences, as well as the potential of probiotics to restore eubiosis is also discussed.
In cancer, corrupted neoplastic cell successfully evades the immune attack using two main strategies: avoiding the immune recognition and instigating an immunosuppressive tumor microenvironment. Cancer is able to induce immune tolerance and present itself to immune system as normal tissue. There is a defect in immune tolerance: the tolerance is wrongly induced toward cancer. In autoimmune diseases, immune system attacks normal tissue because it fails to recognize its own constituent parts as self. There is a defect in immune tolerance: the tolerance is lost toward normal tissues. In both diseases wrong information in the communication between tissue (neoplastic) cells and immune system is crucial: in cancer, neoplastic cells avoid immune attack, whilst in autoimmune diseases, immune system attacks normal cells.
Commensal microorganisms (the microbiota) live on all the surface barriers of our body and are particularly abundant and diverse in the distal gut. The microbiota and its larger host represent a metaorganism in which the cross talk between microbes and host cells is necessary for health, survival, and regulation of physiological functions locally, at the barrier level, and sys-temically. The ancestral molecular and cellular mechanisms stemming from the earliest interactions between prokaryotes and eukaryotes have evolved to mediate microbe-dependent host physiology and tissue homeostasis, including innate and adaptive resistance to infections and tissue damage. Mostly because of its effects on metabolism, cellular proliferation, inflammation, and immunity, the microbiota regulates cancer at the level of predisposing conditions, initiation, genetic instability, susceptibility to host immune response , progression, comorbidity, and response to therapy. Here, we review the mechanisms underlying the interaction of the microbiota with cancer and the evidence suggesting that the microbiota could be targeted to improve therapy while attenuating adverse reactions.
Microbial induction of immunity, inflammation, and cancer
Frontiers in physiology, 2011
The human microbiota presents a highly active metabolic that influences the state of health of our gastrointestinal tracts as well as our susceptibility to disease. Although much of our initial microbiota is adopted from our mothers, its final composition and diversity is determined by environmental factors. Westernization has significantly altered our microbial function. Extensive experimental and clinical evidence indicates that the westernized diet, rich in animal products and low in complex carbohydrates, plus the overuse of antibiotics and underuse of breastfeeding, leads to a heightened inflammatory potential of the microbiota. Chronic inflammation leads to the expression of certain diseases in genetically predisposed individuals. Antibiotics and a "clean" environment, termed the "hygiene hypothesis," has been linked to the rise in allergy and inflammatory bowel disease, due to impaired beneficial bacterial exposure and education of the gut immune system, w...
Microbiota in cancer development and treatment
Journal of Cancer Research and Clinical Oncology, 2018
Purpose Human microbiota comprises of a variety of organisms ranging from bacterial species to viruses, fungi, and protozoa which are present on the epidermal and mucosal barriers of the body. It plays a key role in health and survival of the host by regulation of the systemic functions. Its apparent functions in modulation of the host immune system, inducing carcinogenesis and regulation of the response to the cancer therapy through a variety of mechanisms such as bacterial dysbiosis, production of genotoxins, pathobionts, and disruption of the host metabolism are increasingly becoming evident. Methods Different electronic databases such as PubMed, Google Scholar, and Web of Science were searched for relevant literature which has been reviewed in this article. Results Characterization of the microbiome particularly gut microbiota, understanding of the host-microbiota interactions, and its potential for therapeutic exploitation are necessary for the development of novel anticancer therapeutic strategies with better efficacy and lowered off-target side effects. Conclusion In this review, the role of microbiota is explained in carcinogenesis, mechanisms of microbiota-mediated carcinogenesis, and role of gut microbiota in modulation of cancer therapy.
Editorial: Host-microbiota and cancer
Frontiers in Oncology
Cancer is the 2 nd leading cause of death in the United States, making up an average of 21% of deaths in both genders (1). The COVID-19 pandemic impacted the diagnosis and treatment of cancer, starting from its peak in mid-2020 and still recovering (2). With continued mortality and incidence due to this disease, research has migrated to other areas of interest for mechanisms to aid cancer management, such as exosomes, nucleic acids, and, more innovatively, the gut microbiota. The human microbiome is a complex community composed of various microorganisms, including bacteria, viruses, fungi, and protozoans. It contains approximately 100 trillion microorganisms and can be found at different body points, such as the skin and respiratory system. Still, the majority commonly reside in the gastrointestinal region (3). The connection between microbiome and health began to be established with the microbiome having evolving links in cardiovascular, inflammatory bowel disease, and cancer (4-6). Within the scope of cancer, it is now well known that a high involvement of microbiota can indirectly or directly affect the occurrence, treatment outcome, and drug resistance. For example, Helicobacter pylori are cancer-related pathogen that can increase the incidence of gastric cancer (7). This microorganism and others will generally be responsible for approximately 20% of cancer cases (8). Additionally, the microbiota in the body has been found to have interactions in the tumor microenvironment and has ways to promote or regulate carcinogenesis and cancer therapeutic response. This can occur through signaling pathways, inducing DNA damage, and immune system regulation (9). The ability of the human microbiota to play a functional role in carcinogenesis identifies it as a potential and worthy subject for further research to understand the regulatory mechanisms for pathogen-related cancers. Furthermore, research is essential and beneficial as it can aid in identifying novel therapeutics for cancer management. Studies have shown that the tumor microbiota has a different composition than normal, and the type of composition can affect different points of development and progression. The microbiome can help regulate cancer at various points and is commonly due to the significant difference in the microbiota composition. Therefore, understanding how the Frontiers in Oncology frontiersin.org 01
Libri Oncologici Croatian Journal of Oncology, 2021
The aim of this review paper is to present the complex interactions between microbiome and the host and the importance of the microbiome in maintaining homeostasis. The ways by which oncomicrobes can influence cancer development, and ultimately the possible impact of the microbiome on the cancer treatment, are reviewed. Microbiome is a community of trillions of microbes and their structural elements, with significant medical potential. It is thought that the microbiome's genome contains approximately 300 times more genes than the human genome. Microbiome is crucial for the homeostasis and well been of an organism. Dysbiosis in the microbiome can lead to developing of various negative impacts on an organism, including carcinogenesis. For some oncomicrobes is has been conclusively proven to be biological carcinogens, and for many others, there is an evidence of their possible involvement in carcinogenesis. Studies have shown that the microbiome can have an impact on every type of medical treatment, including anticancer therapy, by changing its effectiveness and toxicity. Future microbiome research will undoubtedly enable to open new possibilities in the fields of treatments and early diagnosis of cancer.