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      Next generation probiotics in disease amelioration

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          Abstract

          Studies on the role of gut commensal bacteria in health development have rapidly attracted much more attention beyond the classical pathogens over the last decade. Many important reports have highlighted the changes in the gut microbiota (dysbiosis) are closely related to development of intra- and extra-intestinal, chronic inflammation related diseases such as colitis, obesity/metabolic syndromes, diabetes mellitus, liver diseases, cardiovascular diseases and also cancer and neurodegenerative diseases. To circumvent these difficulties, the strategy of modulating the structure of the gut microbiota has been under intensive study and shed more light on amelioration of these inflammation related diseases. While traditional probiotics generally show marginal ameliorative effects, emerging next generation probiotics start to reveal as new preventive and therapeutic tools. Recent studies have unraveled many potential next generation probiotics (NGP). These include Prevotella copri and Christensenella minuta that control insulin resistance, Parabacteroides goldsteinii, Akkermansia muciniphila and Bacteroides thetaiotaomicron that reverse obesity and insulin resistance, Faecalibacterium prausnitzii that protects mice against intestinal diseases, and Bacteroides fragilis that reduces inflammation and shows anticancer effect. New agents will soon be revealed for targeted therapy on specific inflammation related diseases. The important roles of next generation probiotics and gut microbiota normobiosis on the maintenance of intestinal integrity and homeostasis are emphasized.

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          Most cited references67

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          Gut microbiome influences efficacy of PD-1–based immunotherapy against epithelial tumors

          Immune checkpoint inhibitors (ICI) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizeable minority of cancer patients. Here, we show that primary resistance to ICI can be due to abnormal gut microbiome composition. Antibiotics (ATB) inhibited the clinical benefit of ICI in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICI (but not from non-responding patients) into germ-free or ATB-treated mice ameliorated the antitumor effects of PD-1 blockade. Metagenomics of patient stools at diagnosis revealed correlations between clinical responses to ICI and the relative abundance of Akkermansia muciniphila. Oral supplementation with A. muciniphila post-FMT with non-responder feces restored the efficacy of PD-1 blockade in an IL-12-dependent manner, by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into tumor beds.
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            Gut microbiome modulates response to anti–PD-1 immunotherapy in melanoma patients

            Pre-clinical 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-PD-1 immunotherapy (n=112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders (R) versus non-responders (NR). Analysis of patient fecal microbiome samples (n=43, 30R, 13NR) showed significantly higher alpha diversity (p<0.01) and relative abundance of Ruminococcaceae bacteria (p<0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in R including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and anti-tumor 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.
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              Role of the microbiota in immunity and inflammation.

              The microbiota plays a fundamental role on the induction, training, and function of the host immune system. In return, the immune system has largely evolved as a means to maintain the symbiotic relationship of the host with these highly diverse and evolving microbes. When operating optimally, this immune system-microbiota alliance allows the induction of protective responses to pathogens and the maintenance of regulatory pathways involved in the maintenance of tolerance to innocuous antigens. However, in high-income countries, overuse of antibiotics, changes in diet, and elimination of constitutive partners, such as nematodes, may have selected for a microbiota that lack the resilience and diversity required to establish balanced immune responses. This phenomenon is proposed to account for some of the dramatic rise in autoimmune and inflammatory disorders in parts of the world where our symbiotic relationship with the microbiota has been the most affected. Copyright © 2014 Elsevier Inc. All rights reserved.
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                Author and article information

                Journal
                J Food Drug Anal
                J Food Drug Anal
                Journal of Food and Drug Analysis
                Taiwan Food and Drug Administration
                1021-9498
                2224-6614
                2019
                02 February 2019
                : 27
                : 3
                : 615-622
                Affiliations
                [a ]Department of Medical Biotechnology and Laboratory Science, College of Medicine, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan
                [b ]Microbiota Research Center and Emerging Viral Infections Research Center, Chang Gung University, Gueishan, Taoyuan 33302, Taiwan
                [c ]Chang Gung Immunology Consortium, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan
                [d ]Department of Laboratory Medicine, Linkou Chang Gung Memorial Hospital, Gueishan, Taoyuan, 33305, Taiwan
                [e ]Research Center for Chinese Herbal Medicine, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taoyuan, 33303, Taiwan
                [f ]Research Center for Food and Cosmetic Safety, College of Human Ecology, Chang Gung University of Science and Technology, Gueishan, Taoyuan 33303, Taiwan
                [g ]Department of Medicine, College of Medicine, Chang Gung University, Gueishan, Taoyuan, 33302, Taiwan
                [h ]Department of Respiratory Therapy, Fu Jen Catholic University, Xinzhuang, New Taipei City, 24205, Taiwan
                [i ]Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan
                Author notes
                [* ]Corresponding author. Department of Respiratory Therapy, College of Medicine, Fu Jen Catholic University Hospital and Fu Jen Catholic University, 510 Zhong-Zheng Road, Xinzhuang Dist., New Taipei City 24205, Taiwan.
                [** ]Corresponding author. Department of Medical Biotechnology and Laboratory Science, and Microbiota Research Center, Chang Gung University, 259 Wen-Hwa 1st Road, Guei-Shan, Tao-Yuan, 333, Taiwan. E-mail addresses: 082385@ 123456mail.fju.edu.tw (C.-C. Lu), hclai@ 123456mail.cgu.edu.tw (H.-C. Lai).
                [1]

                Authors contribute equally to this article.

                Article
                jfda-27-03-615
                10.1016/j.jfda.2018.12.011
                9307044
                31324278
                ece43890-83d9-4d88-a542-7ef2ced8a211
                © 2019 Taiwan Food and Drug Administration

                This is an open access article under the CC-BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 28 September 2018
                : 20 December 2018
                : 27 December 2018
                Categories
                Review Article

                microbiota,microbiome,prebiotic,probiotic,metabolites
                microbiota, microbiome, prebiotic, probiotic, metabolites

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