VastBiome

<p><a href="https://www.sciencemag.org/news/2019/04/fecal-transplants-could-help-patients-cancer-immunotherapy-drugs">Fecal transplants could help patients on cancer immunotherapy drugs</a></p> <p>Oncologists deploy an array of strategies to stop cancer, from chemotherapy to radiation to drugs that boost the body&rsquo;s immune defenses. Now, another potential therapy is being tested in clinical studies: fecal transplants. Early results from two groups described at the annual meeting of the American Association for Cancer Research (AACR) here this week suggest some patients who initially did not benefit from immunotherapy drugs saw their tumors stop growing or even shrink after receiving a stool sample from patients for whom the drugs worked.&nbsp;&nbsp;</p> <p>&nbsp;<a href="https://www.ncbi.nlm.nih.gov/pubmed/27058662">Microbiome and Anticancer Immunosurveillance</a></p> <p>Anticancer immune responses can be considered a desirable form of autoimmunity that may be profoundly shaped by the microbiome. Here, we discuss evidence for the microbiome&#39;s influence on anti-tumor immunosurveillance, including those that are indirect and can act at a distance, and we put forward hypotheses regarding mechanisms of how these effects are implemented. These may involve cross-reactivity between microbial and tumor antigens shaping T cell repertoires and/or microbial products stimulating pattern recognition receptors that influence the type and intensity of immune responses. Understanding how the microbiome impacts natural cancer immunosurveillance as well as treatment-induced immune responses will pave the way for more effective therapies and prophylactics.</p> <p><a href="https://www.ncbi.nlm.nih.gov/pubmed/31450712">Gut Microbiome: A promising biomarker for immunotherapy and colorectal cancer</a></p> <p>Research has been driven towards finding therapy predictive biomarkers for colorectal cancer (CRC) with a special interest in studying the gut microbiome. Gut microbiome acts not only as a barrier to prevent bacterial invasion and infection, but it also affects the efficacy of hematopoietic-cell transplantation, chemotherapy, and immunotherapy. Recently, immunotherapy, which potentiates the host immune system, has revolutionized cancer therapy in general and CRC treatment specifically by increasing the quality of life and the survival of a subset of patients with this disease. In immunotherapy, the gut microbiome plays an important role in cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) blockade, programmed cell death protein 1 (PD-L1) mediation, and T cell stimulation. As such, this review will cover the role of gut microbiome in CRC, summarize approved immunotherapy treatments for CRC, and focus on the potential use of gut microbiome as a biomarker for immunotherapy.</p> <p><a href="https://www.ncbi.nlm.nih.gov/pubmed/31400112">A deep learning genome-mining strategy for biosynthetic gene cluster prediction</a></p> <p>Natural products represent a rich reservoir of small molecule drug candidates utilized as antimicrobial drugs, anticancer therapies, and immunomodulatory agents. These molecules are microbial secondary metabolites synthesized by co-localized genes termed Biosynthetic Gene Clusters (BGCs). The increase in full microbial genomes and similar resources has led to development of BGC prediction algorithms, although their precision and ability to identify novel BGC classes could be improved. Here we present a deep learning strategy (DeepBGC) that offers reduced false positive rates in BGC identification and an improved ability to extrapolate and identify novel BGC classes compared to existing machine-learning tools. We supplemented this with random forest classifiers that accurately predicted BGC product classes and potential chemical activity. Application of DeepBGC to bacterial genomes uncovered previously undetectable putative BGCs that may code for natural products with novel biologic activities. The improved accuracy and classification ability of DeepBGC represents a major addition to in-silico BGC identification.</p> <p><a href="https://science.sciencemag.org/content/359/6371/97">Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients</a></p> <p>Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti&ndash;programmed cell death 1 protein (PD-1) immunotherapy (<em>n</em>&nbsp;= 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (<em>n&nbsp;</em>= 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (<em>P&nbsp;</em>&lt; 0.01) and relative abundance of bacteria of the Ruminococcaceae family (<em>P&nbsp;</em>&lt; 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.</p> <p>We have not submitted for regulatory approval as of yet.&nbsp; We are focused on preclinical validation and testing our biomarker on clinical trials&nbsp;</p>