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. In November, University of Chicago researchers wrote that giving mice Bifidobacterium, which normally resides in the gastrointestinal tract, was as effective as an immunotherapy in controlling the growth of skin cancer. Combining the two practically eliminated tumor growth. 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.
Current models of GI mucositis pathophysiology are generally silent on the role of the intestinal microbiome. Aim To identify functional mechanisms by which the intestinal microbiome may play a key role in the pathophysiology of GI mucositis, we applied high-throughput DNA-sequencing analysis to identify microbes and microbial functions that are modulated following chemotherapy. Methods We amplified and sequenced 16S rRNA genes from faecal samples before and after chemotherapy in 28 patients with non-Hodgkin's lymphoma who received the same myeloablative conditioning regimen and no other concomitant therapy such as antibiotics. Results Conclusions. 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. Related to cancer in general, about 650,000 Americans get chemotherapy, in one form or another, each year. One recent study, looking at the effects of chemotherapy on the microbiome, evaluated patients who were receiving chemo to prepare them for stem cell therapy. Typically, when the chemotherapy agent is administered, there is irritation of the gut (mucositis), and, likely, this is what provoked the researchers to study the microbiome of these individuals.
Read Next June 10, 2015. The breakthrough of the microbiota | Nature Reviews Immunology. 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 | Microbiome | Full Text. 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. The consequences of decreased bacterial diversity in human milk and the implications on the child are still unknown; however, the decreased milk diversity could impact intestinal diversity and it has been shown that low intestinal diversity in the first weeks of life is associated with necrotizing enterocolitis [30] and an increased risk of allergy and atopy in school-age children [31].
Lower intestinal diversity has also been observed in children with type 1 diabetes compared to age-matched controls [32]. The utilization of bacterial products by other bacteria is termed metabolic cross-feeding and plays an important role in bacterial selection. 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 | GEN. 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.
"Now, it's becoming clear that variations in one's gut microbiome--the population of bacteria and other microbes that live in the digestive tract--can also influence the effects of treatment. " Irinotecan is administered intravenously in an inactive form. In the current study, Dr. 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. Gut bacteria has been found to potentially play a role in PTSD, Alzheimer's, obesity, diabetes and even aging. Numerous studies have also found causal connections between gut bacteria and the efficacy of certain drugs, from those as simple as ibuprofen, to more complex interactions with HIV-prevention treatments. Webinar Review: Immuno-oncology and the Microbiome | Taconic Biosciences. 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. Modulation of the Microbiome as a Therapeutic Strategy “Germ-free mice do represent a critical tool for investigation of the microbiome.”– Dr. Two new papers demonstrated that the patient gut microbiome does indeed affect response to cancer immunotherapy3,4.
Dr. Considerations for Preclinical Studies Dr. Dr. References: 1. 2. 3. 4. 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. Results of this work were published in the journal Science on 22 November 2013. Author’s bio : Dr. 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. Next, the researchers decided to test the effects of an anti-PD-L1 immunotherapy antibody. M. A. 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.
“That’s really quite unique.” Blaser echoed this sentiment. N. Gut Bacteria Predict Responses, Survival Time to PD-1 Cancer Immunotherapy | Cancer Network | The Oncology Journal. 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. Previously reported mouse studies suggested that the bacterial composition of the gut microbiome can modulate responses to anticancer immunotherapy, possibly explaining why mice purchased from different companies exhibit different responses to PD-1 inhibitors. The new studies were undertaken to determine whether or not the composition of human gut microbiomes similarly modulates responses to PD-1–based immunotherapy in patients with melanoma or other cancers. Gut bacteria diversity and composition indeed predicted PD-1 inhibitor responses among patients with melanoma, Dr.
Dr. 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. This allows cancers to evade the immune system and proliferate.
At a therapeutic level, these new patient-based results are highly encouraging. There were aspects of general agreement between the two studies. The role of gut microbiota in host responses to cancer immunotherapy - Gut Microbiota for Health. Bacteria and Cancer Immunotherapy: What’s in Your Gut? - Medical News Bulletin | Health News and Medical Research. 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.
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. Tuning the Microbiome Improves Melanoma Immunotherapy Response | GEN. Melanoma cancer therapy’s efficacy may depend on the existence of specific gut bacteria — The American Microbiome Institute. 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. Gut bacteria diversity linked to immunotherapy response in melanoma patients.