Study: Leaky Gut and Chemo
Study: Leaky Gut and Chemo
Reference
russo f, lenssalata m, clemente c, et al. The effects of Fluorouracil, Epirubicin and Cyclophosphamide (FEC60) on the intestinal barrier function and intestinal work at breast cancer patients: an observation study. BMC-Krebs. 4th February 2013; 1:56 p.m.
Design
prospective observation study of consecutive patients
participant
60 breast cancer patients took part in the study, who had undergone surgical removal of the tumor and the lymph nodes and received adjuvant chemotherapy. 37 patients completed the study. With the help of a questionnaire it was determined in which patient diarrhea occurred
study medication and dosage
All participants received the same chemotherapy FEC-60 (Fluorouracil 600 mg/m2, Epirubicin 60 mg/m2 and cyclophosphamide 600 mg/m2 every 21 days over 6 cycles).
target parameter
During chemotherapy, intestinal permeability was assessed by lactulose/mannitol (LA/MA) urint test on the days 0 and 14. The concentrations of different GI-peptides, especially zonulin, glucagon-like peptide-2 (GLP-2), epidermal growth factor (EGF). ) and Ghrelin were measured by elisa tests at 5 times (days 0, 3, 10, 14 and 21).
As the authors explain, Zonulin modulates the mucosal barrier by dissolving the Tight Junctions in inflammation and plays a "role in the pathogenesis of autoimmune diseases such as celiac disease and type 1 diabetes". The authors find that GLP-2 is an "intestinotropic growth hormone that promotes many aspects of intestinal function, including a quick improvement in the growth of mucosa and the bowel function". It is believed that EGF and GLP-2 protect against chemotherapy damage to the intestinal mucosa. Ghrelin, which is produced by enteroendocrine cells of the gastrointestinal tract, is "involved in the control of the mucous membrane barrier and is considered a potential means of protection against chemotherapy complications." In mice it could be shown that Ghrelin's administration prevents the doxorubicin-induced damage to the gastrointestinal mucosa. ”
most important knowledge
During chemotherapy, the Lactulose Mannitol ratio increased significantly up to the 14th day compared to the initial value. The zonuline level remained unaffected. The GLP-2 and EGF levels sank significantly. The GLP-2 values were significantly lower on the 14th day than on 0. And 3rd day, while the EGF values were significantly lower on the 10th day than at the starting value.
Several current publications indicate that this increase in permeability and the resulting bacterial translocation are important for several chemotherapeutic agents. . . For the cancer -inhibiting effect of the medication.
GHRELIN rose significantly on day 3 compared to the days 0 and 21. Ten patients (27 %) suffered from diarrhea. On the 14th day of chemotherapy, patients with diarrhea compared to patients without diarrhea occurred a significant increase in the LA/MA ratio. Patients with diarrhea had significantly lower GLP-2 and higher ghrelin values.
In the patient with diarrhea, an opposite correlation between Blp-2 and the LA/MA relationship was observed on the 14th day. All patients showed a significantly increased intestinal permeability and shifts of GLP-2, Ghrelin and EGF. Those who developed diarrhea during treatment had another GI peptide profile.
effects on practice
These results should not surprise a clinician. Cancer patients that undergo treatment often develop diarrhea, and it can be assumed that this is related to increased intestinal perpermitivity. The question is what we do about it, if at all.
This FEC-60 medication cocktail is not the only one caused by intestinal damage. Other cancer treatments are associated with increased intestinal permeability. For example Bevacizumab, Oxaliplatin, 5-Fluorourouracil and LeucoFORIN, 2 also the abdominal radiation, which causes its own special form of gastritis, is accompanied by an increased permeability.
What many people should surprise is that this increase in permeability may be a good thing.
Several recent work indicates that this increase in permeability and the resulting bacterial translocation for the cancer -fighting effect of the medication is important for several chemotherapeutic agencies - in particular the platinum medication and cyclophosphamide.
in an article published in the November edition 2013 science Viaud et al. suggested that certain chemotherapeutic agents only have an indirect effect against cancer; Their primary mechanism of action is to trigger the intestinal permeability, which in turn leads to shift bacteria from the intestine into the body, where its presence triggers an immune response. that caused cyclophosphamide devastating damage to the intestinal mucosa; The villi shrank and the permeability of the small intestine increased. Several types of bacteria, especially gram -positive bacteria, have immigrated to the body. Two lactobacillus types and Enterococcus Hirae bacteria came to the lymph nodes and the spleen. This migration could be of crucial importance for the effect of the medication. In vitro studies indicate that these gram-positive bacteria lead to immaturity T cells first convert into TH17 cells and later convert some of them into memory cells, which enables an extended immune response to the tumor. Cancer mice that were bred or treated with antibiotics that kill these gram-positive bacteria did not increase the TH17 cells if they were treated with cyclophosphamide. It is even more important that the medication no longer let their tumors shrink.
In a parallel work, iida et al. that intestinal bacteria are necessary for the effect of platinum medications.
oxaliplatin typically at least partially acts in part by increasing the reactive oxygen species (ROS) in cancer cells, which leads to the apoptosis of the cancer cells. In a study with mice that have been implanted by different types of cancer, Iida's group treated half of the animals with antibiotics before giving oxaliplatin. The mice that were missing bacteria did not increase the ROS. 80 % of the mice treated with antibiotics died within 3 weeks. The mice that were not given antibiotics still had a normal intestinal flora and they were much better; They increased ROS production and 80 % were still alive.
At least for mice, intestinal bacteria are necessary so that certain types of chemotherapy work. Domino Trincheiri, one of the main authors, is quoted in "Science" with the words: "We suspect that platinum therapy could involve an immunch therapy on which the intestinal microbiota could have a modulating effect, but we were surprised at how strongly the inflammatory cells reacted." The production of oxygen species strictly depended on the presence of intestinal microbiota. ”
This is a new point of view. Until the publication of these studies in science We considered the bacterial translocation as part of the problem. These wandering bacteria are held responsible for cancer cachexia and are considered the "therapeutic goal" and the cause of many side effects. 7.8 Our treatment goal was the prevention of diarrhea and leader intestinal. Melatonin, assuming that we do the right thing.
At least with cyclophosphamide and platinum medication, we should perhaps choose therapies that increase intestinal permeability, such as piperine or fasting, in the hope of achieving a greater cytotoxic effect through chemotherapy.
This is heretical thinking - the opposite of what we have been thinking or doing for years. Of course, these ideas only come from mouse studies; These results may not be confirmed in humans. However, if this is the case, a serious restructuring of our treatment strategies is required.
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