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Advances in Cancer Research 2022Chemotherapy-induced gastrointestinal dysfunction is a common occurrence associated with many different classes of chemotherapeutic agents. Gastrointestinal toxicity... (Review)
Review
Chemotherapy-induced gastrointestinal dysfunction is a common occurrence associated with many different classes of chemotherapeutic agents. Gastrointestinal toxicity includes mucositis, diarrhea, and constipation, and can often be a dose-limiting complication, induce cessation of treatment and could be life threatening. The gastrointestinal epithelium is rich in rapidly dividing cells and hence is a prime target for chemotherapeutic drugs. The incidence of gastrointestinal toxicity, including diarrhea and mucositis, is extremely high for a wide array of chemotherapeutic and radiation regimens. In fact, 60%-100% of patients on high-dose chemotherapy suffer from gastrointestinal side effects. Unfortunately, treatment options are limited, and therapy is often restricted to palliative care. Therefore, there is a great unmet therapeutic need for preventing and treating chemotherapy-induced gastrointestinal toxicities in the clinic. In this review, we discuss our current understanding of the mechanisms underlying chemotherapy-induced diarrhea and mucositis, and emerging mechanisms involving the enteric nervous system, smooth muscle cells and enteric immune cells. Recent evidence has also implicated gut dysbiosis in the pathogenesis of not only chemotherapy-induced mucositis and diarrhea, but also chemotherapy-induced peripheral neuropathy. Oxidative stress induced by chemotherapeutic agents results in post-translational modification of ion channels altering neuronal excitability. Thus, investigating how chemotherapy-induced changes in the gut- microbiome axis may lead to gut-related toxicities will be critical in the discovery of new drug targets for mitigating adverse gastrointestinal effects associated with chemotherapy treatment.
Topics: Antineoplastic Agents; Diarrhea; Gastrointestinal Microbiome; Humans; Mucositis; Neoplasms
PubMed: 35779873
DOI: 10.1016/bs.acr.2022.02.007 -
Glutamine for Amelioration of Radiation and Chemotherapy Associated Mucositis during Cancer Therapy.Nutrients Jun 2020Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit... (Review)
Review
Glutamine is a major dietary amino acid that is both a fuel and nitrogen donor for healing tissues damaged by chemotherapy and radiation. Evidence supports the benefit of oral (enteral) glutamine to reduce symptoms and improve and/or maintain quality of life of cancer patients. Benefits include not only better nutrition, but also decreased mucosal damage (mucositis, stomatitis, pharyngitis, esophagitis, and enteritis). Glutamine supplementation in a high protein diet (10 grams/day) + disaccharides, such as sucrose and/or trehalose, is a combination that increases glutamine uptake by mucosal cells. This increased topical effect can reduce painful mucosal symptoms and ulceration associated with chemotherapy and radiation in the head and neck region, esophagus, stomach and small intestine. Topical and oral glutamine seem to be the preferred routes for this amino acid to promote mucosal healing during and after cancer treatment.
Topics: Antineoplastic Agents; Diet, High-Protein; Dietary Proteins; Dietary Sucrose; Dietary Supplements; Glutamine; Humans; Malnutrition; Mucositis; Mucous Membrane; Neoplasms; Radiotherapy; Trehalose; Wound Healing
PubMed: 32512833
DOI: 10.3390/nu12061675 -
Trends in Endocrinology and Metabolism:... Aug 2023Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects.... (Review)
Review
Cancer remains the second leading cause of mortality, with nearly 10 million deaths worldwide in 2020. In many cases, radiotherapy is used for its anticancer effects. However, radiation causes healthy tissue toxicity as a side effect. In intra-abdominal and pelvic malignancies, the healthy bowel is inevitably included in the radiation field, causing radiation-induced enteritis and dramatically affecting the gut microbiome. This condition is associated with significant morbidity and mortality that impairs cancer patients' and survivors' quality of life. This Review provides a critical overview of the main drivers in modulating the gut microenvironment in homeostasis, disease, and injury, focusing on gut microbial metabolites and microorganisms that influence epithelial regeneration upon radiation injury.
Topics: Humans; Gastrointestinal Microbiome; Quality of Life; Enteritis; Radiation Injuries; Neoplasms; Regeneration; Tumor Microenvironment
PubMed: 37336645
DOI: 10.1016/j.tem.2023.05.006 -
Frontiers in Cellular and Infection... 2021Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in... (Review)
Review
Radiotherapy is an important treatment for abdominal tumors. A critical side effect for this therapy is enteritis. In this review, we aim to summarize recent findings in radiation enteritis, in particular the role of gut microbiota dysbiosis in the development and therapy of the disease. Gut microbiota dysbiosis plays an important role in the occurrence of various diseases, such as radiation enteritis. Abdominal radiation results in changes in the composition of microbiota and reduces its diversity, which is mainly reflected in the decrease of spp. and spp. and increase of and spp. Gut microbiota dysbiosis aggravates radiation enteritis, weakens intestinal epithelial barrier function, and promotes inflammatory factor expression. Pathogenic induce the rearrangement and redistribution of claudin-1, occludin, and ZO-1 in tight junctions, a critical component in intestinal epithelial barrier. In view of the role that microbiome plays in radiation enteritis, we believe that intestinal flora could be a potential biomarker for the disease. Correction of microbiome by application of probiotics, fecal microbiota transplantation (FMT), and antibiotics could be an effective method for the prevention and treatment of radiation-induced enteritis.
Topics: Dysbiosis; Enteritis; Fecal Microbiota Transplantation; Gastrointestinal Microbiome; Humans; Intestines; Probiotics
PubMed: 34395308
DOI: 10.3389/fcimb.2021.586392 -
Gastroenterology Research Dec 2022The benefit of radiation is immense in the field of gastroenterology. Radiation is used daily in different gastrointestinal imaging and diagnostic and therapeutic... (Review)
Review
The benefit of radiation is immense in the field of gastroenterology. Radiation is used daily in different gastrointestinal imaging and diagnostic and therapeutic interventional procedures. Radiotherapy is one of the primary modalities of treatment of gastrointestinal malignancies. There are various modalities of radiotherapy. Radiotherapy can injure malignant cells by directly damaging DNA, RNA, proteins, and lipids and indirectly by forming free radicals. External beam radiation, internal beam radiation and radio-isotope therapy are the major ways of delivering radiation to the malignant tissue. Radiation can also cause inflammation, fibrosis, organ dysfunction, and malignancy. Patients with repeated exposure to radiation for diagnostic imaging and therapeutic procedures are at slightly increased risk of malignancy. Gastrointestinal endoscopists performing fluoroscopy-guided procedures are also at increased risk of malignancy and cataract formation. The radiological protection society recommends certain preventive and protective measures to avoid side effects of radiation. Gastrointestinal complications related to radiation therapy for oncologic processes, and exposure risks for patients and health care providers involved in diagnostic or therapeutic imaging will be discussed in this review.
PubMed: 36660465
DOI: 10.14740/gr1567 -
Nature Communications Mar 2022Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need....
Protecting the whole small intestine from radiation-induced intestinal injury during the radiotherapy of abdominal or pelvic solid tumors remains an unmet clinical need. Amifostine is a promising selective radioprotector for normal tissues. However, its oral application in intestinal radioprotection remains challenging. Herein, we use microalga Spirulina platensis as a microcarrier of Amifostine to construct an oral delivery system. The system shows comprehensive drug accumulation and effective radioprotection in the whole small intestine that is significantly superior to free drug and its enteric capsule, preventing the radiation-induced intestine injury and prolonging the survival without influencing the tumor regression. It also shows benefits on the gut microbiota homeostasis and long-term safety. Based on a readily available natural microcarrier, this work presents a convenient oral delivery system to achieve effective radioprotection for the whole small intestine, providing a competitive strategy with great clinical translation potential.
Topics: Gastrointestinal Microbiome; Homeostasis; Humans; Intestines; Microalgae; Neoplasms; Radiation-Protective Agents
PubMed: 35301299
DOI: 10.1038/s41467-022-28744-4 -
Nature Oct 2019Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3s and neuronal cells have been shown to...
Group 3 innate lymphoid cells (ILC3s) are major regulators of inflammation, infection, microbiota composition and metabolism. ILC3s and neuronal cells have been shown to interact at discrete mucosal locations to steer mucosal defence. Nevertheless, it is unclear whether neuroimmune circuits operate at an organismal level, integrating extrinsic environmental signals to orchestrate ILC3 responses. Here we show that light-entrained and brain-tuned circadian circuits regulate enteric ILC3s, intestinal homeostasis, gut defence and host lipid metabolism in mice. We found that enteric ILC3s display circadian expression of clock genes and ILC3-related transcription factors. ILC3-autonomous ablation of the circadian regulator Arntl led to disrupted gut ILC3 homeostasis, impaired epithelial reactivity, a deregulated microbiome, increased susceptibility to bowel infection and disrupted lipid metabolism. Loss of ILC3-intrinsic Arntl shaped the gut 'postcode receptors' of ILC3s. Strikingly, light-dark cycles, feeding rhythms and microbial cues differentially regulated ILC3 clocks, with light signals being the major entraining cues of ILC3s. Accordingly, surgically or genetically induced deregulation of brain rhythmicity led to disrupted circadian ILC3 oscillations, a deregulated microbiome and altered lipid metabolism. Our work reveals a circadian circuitry that translates environmental light cues into enteric ILC3s, shaping intestinal health, metabolism and organismal homeostasis.
Topics: ARNTL Transcription Factors; Animals; Biological Clocks; Brain; Circadian Rhythm; Cues; Feeding Behavior; Female; Gastrointestinal Microbiome; Homeostasis; Immunity, Innate; Intestines; Light; Lipid Metabolism; Lymphocytes; Male; Mice; Photoperiod
PubMed: 31534216
DOI: 10.1038/s41586-019-1579-3 -
Frontiers in Pharmacology 2023Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause... (Review)
Review
Radiotherapy is widely used in clinic due to its good effect for cancer treatment. But radiotherapy of malignant tumors in the abdomen and pelvis is easy to cause radiation enteritis complications. Gastrointestinal tract contains numerous microbes, most of which are mutualistic relationship with the host. Abdominal radiation results in gut microbiota dysbiosis. Microbial therapy can directly target gut microbiota to reverse microbiota dysbiosis, hence relieving intestinal inflammation. In this review, we mainly summarized pathogenesis and novel therapy of the radiation-induced intestinal injury with gut microbiota dysbiosis and envision the opportunities and challenges of radiation enteritis therapy.
PubMed: 37063268
DOI: 10.3389/fphar.2023.1116558 -
Gut Microbes Jul 2020Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we...
BACKGROUND
Hematopoietic and intestinal systems side effects are frequently found in patients who suffered from accidental or medical radiation exposure. In this case, we investigated the effects of gut microbiota produced-valeric acid (VA) on radiation-induced injuries.
METHODS
Mice were exposed to total body irradiation (TBI) or total abdominal irradiation (TAI) to mimic accidental or clinical scenarios. High-performance liquid chromatography (HPLC) was performed to assess short-chain fatty acids (SCFAs) in fecal pellets. Oral gavage with VA was used to mitigate radiation-induced toxicity. Gross examination was performed to assess tissue injuries of thymus, spleen and small intestine. High-throughput sequencing was used to characterize the gut microbiota profile. Isobaric tags for relative and absolute quantitation (iTRAQ) were performed to analyze the difference of protein profile. Hydrodynamic-based gene delivery assay was performed to silence KRT1 .
RESULTS
VA exerted the most significant radioprotection among the SCFAs. In detail, VA replenishment elevated the survival rate of irradiated mice, protected hematogenic organs, improved gastrointestinal (GI) tract function and intestinal epithelial integrity in irradiated mice. High-throughput sequencing and iTRAQ showed that oral gavage of VA restored the enteric bacteria taxonomic proportions, reprogrammed the small intestinal protein profile of mice following TAI exposure. Importantly, keratin 1 (KRT1) played a pivotal role in the radioprotection of VA.
CONCLUSIONS
Our findings provide new insights into gut microbiota-produced VA and underpin that VA might be employed as a therapeutic option to mitigate radiation injury in pre-clinical settings.
Topics: Animals; Bacterial Physiological Phenomena; Colitis; Dextran Sulfate; Enteritis; Fatty Acids, Volatile; Female; Gastrointestinal Microbiome; Hematopoietic System; Intestinal Mucosa; Intestine, Small; Intestines; Keratin-1; Male; Mice; Mice, Inbred C57BL; Pentanoic Acids; Proteins; Radiation Injuries, Experimental; Radiation-Protective Agents; Symbiosis
PubMed: 31931652
DOI: 10.1080/19490976.2019.1709387