See jerkface bacteria hiding in tumors and gobbling chemotherapy drugs. How Gut Bacteria Are Shaking Up Cancer Research. Top scientists at Roche Holding AG and AstraZeneca Plc are sizing up potential allies in the fight against cancer: the trillions of bacteria that live in the human body.
"Five years ago, if you had asked me about bacteria in your gut playing an important role in your systemic immune response, I probably would have laughed it off," Daniel Chen, head of cancer immunotherapy research at Roche’s Genentech division, said in a phone interview. "Most of us immunologists now believe that there really is an important interaction there. " Two recent studies published in the journal Science have intrigued Chen and others who are developing medicines called immunotherapies that stimulate the body’s ability to fight tumors. Chemotherapy-driven dysbiosis in the intestinal microbiome - Montassier - 2015 - Alimentary Pharmacology & Therapeutics.
Background Chemotherapy is commonly used as myeloablative conditioning treatment to prepare patients for haematopoietic stem cell transplantation (HSCT).
Chemotherapy leads to several side effects, with gastrointestinal (GI) mucositis being one of the most frequent. Chemotherapy and the Microbiome - David Perlmutter M.D. I’ve been receiving a lot of questions lately about the effects of chemotherapy on the gut microbiome.
What I’ve discovered is that there is, in fact, very little literature that explores this information. In reading that, we must recognize that about 90% of all the published literature dealing with the microbiome has been published only in the last 5 years. Chemotherapy as a term actually encompasses a broad array of interventions. Various chemotherapeutic agents are used to target particular diseases. The breakthrough of the microbiota. The fate of the gut microbiome following stem cell transplant — The American Microbiome Institute.
Hematopoietic stem cell transplant (HSCT) is a difficult procedure that is usually administered to patients suffering from bone marrow or blood cancers such as multiple myeloma or leukemia.
Unfortunately, many patients who receive this treatment develop acute graft-versus-host disease (aGvHD), a multi-organ system immunologic disorder that is particularly detrimental to the gastrointestinal tract. In light of increasing evidence highlighting the importance of the symbiosis between the microbiome and human hosts, researchers set out to explore the fate of gut microbiota in pediatric patients who had undergone HSCT. Specifically, phylogenetic profiles and functional properties were examined in a longitudinal analysis to develop a better understanding of the specific role the gut microbiome plays in patients who develop aGvHD following a HSTC procedure. Ten pediatric patients who had undergone HSTC, 5 of which had developed aGvHD, were selected for analysis.
Broad-Spectrum Antibiotics Can Increase GVHD Severity in Stem Cell Recipients. VAL ALTOUNIAN/SCIENCE TRANSLATIONAL MEDICINE Patients who receive blood stem cells from a donor run a risk of developing immediate life-threatening infections and, a month or so later, graft-versus-host disease (GVHD).
But a report published in Science Translational Medicine today (May 18) shows that treating stem cell transplant patients with particular antibiotics might increase GVHD severity. “The key message is that some antibiotics that we routinely use for transplant patients . . . can really amplify the principal nemesis, which is graft-versus-host disease,” said James Ferrara of Mount Sinai Hospital in New York City who was not involved in the study.
“This article starts to illuminate . . . which antibiotics are most harmful and why.” If a person’s immune system is impaired because of, say, leukemia or other blood cancers, it’s possible they will require an infusion of donor blood stem cells—known as an allogeneic hematopoietic stem cell transplantation (allo-HSCT). Y. Effect of chemotherapy on the microbiota and metabolome of human milk, a case report. This study shows that a course of chemotherapy has significant effects on bacterial and metabolic profiles in human milk, moving away from those of healthy lactating women.
Of note, the subject did not report any additional drug use, antibiotics, illness or major changes in diet over the course of the study. Not Just Antibiotics: Is Cancer Chemotherapy Driving Antimicrobial Resistance?: Trends in Microbiology. Gut Microbiota & CA Treatment: New Research and Clinical Relevance – Naturopathic Doctor News and Review. Katherine Hampilos Wendy Hodsdon, ND The gut microbiota, made up of trillions of microorganisms that colonize the distal digestive tract, is required for the development and persistence of a healthy immune response.1 Intestinal immune maturation is dependent on the presence of commensal bacteria for the development of Peyer’s patches, the production of plasma cells and intraepithelial lymphocytes, and the secretion of functional immunoglobulin A (IgA).2 Gut bacteria have also been shown to influence the mature immune system by conditioning mononuclear phagocytes and shaping T-cell responses in the intestine.
Cytotoxic drugs target rapidly dividing cancer cells and induce apoptosis; however, these agents often have low specificity for cancer cells and also damage other rapidly proliferating healthy host tissue. New Research Considerations for Adjunctive Cancer Care Figure 1. References: Kabat AM, Srinivasan N, Maloy KJ. Microbiome Link with Colorectal Cancer Drug Toxicity Points to Predictive Tests and Prevention. Gut bacteria composition could predict toxicity of chemotherapy drugs in cancer patients. November 1, 2017 Albert Einstein College of Medicine researchers report that the composition of people's gut bacteria may explain why some of them suffer life-threatening reactions after taking a key drug for treating metastatic colorectal cancer.
The findings, described online today in npj Biofilms and Microbiomes, a Nature research journal, could help predict which patients will suffer side effects and prevent complications in susceptible patients. "We've known for some time that people's genetic makeup can affect how they respond to a medication," says study leader Libusha Kelly, Ph.D., assistant professor of systems & computational biology and of microbiology & immunology at Einstein. Specific gut bacteria can help or hinder cancer treatments. As medical technology races into the 21st century, the idea of personalized medicine is growing in prominence.
A vastly complex array of factors determine whether a drug works for an individual and evidence is mounting of the important role gut bacteria plays in a person's response to a drug treatment. Two new studies are offering the best evidence to date of this process, showing how the gut microbiome of different patients can affect the success of cancer treatments. In recent years researchers have revealed how our gut microbiome, the large population of bacteria living inside our body, has an incredibly broad and systemic control over our health. Webinar Review: Immuno-oncology and the Microbiome. In a recent webinar, Dr.
Benjamin Cuiffo of Biomodels addressed the role of microbiome in preclinical immuno-oncology research. There is growing evidence that microbial imbalance (dysbiosis) is associated with many illnesses, including inflammation, autoimmune disease, and even cancer — but many researchers fail to account for its impact in preclinical study design. If you missed it, here's a summary of the key developments discussed during Dr. Cuiffo's presentation. Tumor Immunotherapy and the Microbiome There is growing evidence that a patient's microbiome influences both cancer progression and response to therapy. Dr. Cancer Chemotherapy: When intestinal bacteria provide a reinforcement. [This article is an outside contribution by Dr Patricia Lepage (INRA), co-author of the paper. For further references about the author, see the short bio hereunder] Research jointly conducted by investigators at Institut Gustave Roussy, Inserm, Institut Pasteur and INRA (National Agronomic Research Institute) in France has led to a rather surprising discovery on the manner in which cancer chemotherapy treatments act more effectively with the help of the intestinal flora (also known as the intestinal microbiota).
Researchers have shown that the efficacy of one of the molecules most often used in chemotherapy relies to an extent on its capacity to mobilise certain bacteria from the intestinal microbiota toward the bloodstream and lymph nodes. Once inside the lymph nodes, these bacteria stimulate fresh immune defences which then enhance the body’s ability to fight the malignant tumour. Microbes Play Role in Anti-Tumor Response. WIKIMEDIA, NIHThe presence of certain types of gut microbes in mice can boost the anti-tumor effects of cancer immunotherapy, according to two studies from independent research teams published today (November 5) in Science. Cancer immunotherapies that block immune inhibitory pathways are now available as treatments for several tumor types, yet patients’ responses to these therapies vary. Aside from the presence of T cells within the tumor before the start of treatment, it has not been clear what other factors are linked to a response to these antibodies.
The two studies published today, while not the first to suggest that gut microbes can influence the efficacy of cancer therapy, provide a definitive link between gut microbiome composition and cancer immunotherapy response and implicate the positive role of specific bacterial species. Thomas F. Gut Flora Boost Cancer Therapies. WIKIMEDIA, NCIGut microbes—or a lack thereof—can significantly affect the efficacy of certain cancer therapies elsewhere in the body, according to two studies appearing in Science today (November 21). Independent teams show in mouse models of cancer that gut microbes appear to modulate the host immune responses sparked by the anticancer drug cyclophosphamide, as well as by certain types of immunotherapy and chemotherapy. Both found that germ-free mice responded less well to tumor-targeting therapies than animals with rich gut microbiomes.
“Most of the time we think about the gut microbiome shaping the local environment. Now these papers are breaking the glass ceiling and going into extra-intestinal organs . . . and influencing activities of drugs,” said Christian Jobin, a professor of infectious diseases and pathology at the University of Florida who reviewed both studies, and was not involved in either. Gut Bacteria Predict Responses, Survival Time to PD-1 Cancer Immunotherapy. The gut microbiome affects the efficacy of PD-1 immune checkpoint blockade immunotherapy against melanoma and other cancers, according to two studies published in Science. “Our results indicate that the gut microbiome may modulate responses to anti–PD-1 immunotherapy in melanoma patients,” reported lead study author Jennifer Wargo, MD, of the MD Anderson Cancer Center in Houston, Texas, and coauthors.
Microbiota-Regulated Outcomes of Human Cancer Immunotherapy via the PD-1/PD-L1 Axis - Biochemistry (ACS Publications) In recent years, several powerful cancer immunotherapy strategies have passed regulatory approval and have entered the clinic. Collectively, these approaches augment a patient’s own immune surveillance system, directing it to detect and eradicate cancer cells. One such strategy is PD-1/PD-L1 blockade. Normally, on cytotoxic T cells (a type of immune cell that kills cancer cells), the PD-1 receptor, when bound to its ligand PD-L1, acts as a checkpoint to downregulate immune activity (Figure 1).
Crucially, this inhibitory mechanism guards against inflammation associated with autoimmune diseases. However, excessive PD-1 activation, often because the tumor itself overexpresses ligand, prevents cytotoxic T cells from effectively identifying and attacking tumor cells. The role of gut microbiota in host responses to cancer immunotherapy - Gut Microbiota for Health. A recent commentary in Nature Reviews Gastroenterology & Hepatology, written by Dr. Susan E. Bacteria and Cancer Immunotherapy: What’s in Your Gut? - Medical News Bulletin. Strong Evidence Emerging That Gut Microbiome Is a Key Variable in Immunotherapy Efficacy, November 13, 2017.
Adjuvant Probiotics and the Intestinal Microbiome: Enhancing Vaccines and Immunotherapy Outcomes. Probiotics may help prevent chemoradiotherapy-induced diarrhoea in people with abdominal and pelvic cancer - Gut Microbiota for Health. Scientific evidence shows probiotics may have a role in treating acute infectious diarrhoea and preventing antibiotic-associated diarrhoea. However, little is known regarding their role in the treatment of diarrhoea generated as a result of radiotherapy or chemotherapy treatments.
A recent systematic review and meta-analysis, led by Dr. Influence of Orally Administered Probiotic Lactobacillus Strains on Vaginal Microbiota in Women with Breast Cancer during Chemotherapy: A Randomized Placebo-Controlled Double-Blinded Pilot Study. Safety and Efficacy of Fecal Microbiota Transplant for Recurrent Clostridium difficile Infection in Patients With Cancer Treated With Cytotoxic Chemotherapy: A Single-Institution Retrospective Case Series. JavaScript is disabled on your browser. Please enable JavaScript to use all the features on this page.
Tuning the Microbiome Improves Melanoma Immunotherapy Response. Melanoma cancer therapy’s efficacy may depend on the existence of specific gut bacteria — The American Microbiome Institute. Ipilimumab is a monoclonal antibody (mAb) that binds to, and activates T-cells. (Technically, the drug binds to the CTLA-4 receptor on T-cells, which decreases T-cell suppression) It is currently an approved therapy for the treatment of metastatic melanoma.
Unfortunately, activation of the immune system can damage the microbiome, and taking iplimumab often results in adverse side effects in the gut, such as diarrhea. Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients. The commensal microbiome is associated with anti–PD-1 efficacy in metastatic melanoma patients. Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors. Further evidence that the microbiome can improve melanoma cancer therapy — The American Microbiome Institute. Yesterday we discussed a paper that discussed how the microbiome impacted a melanoma cancer therapy. Gut bacteria diversity linked to immunotherapy response in melanoma patients.