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      Exploring the microbiome in health and disease : Implications for toxicology

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          Abstract

          The analysis of human microbiome is an exciting and rapidly expanding field of research. In the past decade, the biological relevance of the microbiome for human health has become evident. Microbiome comprises a complex collection of microorganisms, with their genes and metabolites, colonizing different body niches. It is now well known that the microbiome interacts with its host, assisting in the bioconversion of nutrients and detoxification, supporting immunity, protecting against pathogenic microbes, and maintaining health. Remarkable new findings showed that our microbiome not only primarily affects the health and function of the gastrointestinal tract but also has a strong influence on general body health through its close interaction with the nervous system and the lung. Therefore, a perfect and sensitive balanced interaction of microbes with the host is required for a healthy body. In fact, growing evidence suggests that the dynamics and function of the indigenous microbiota can be influenced by many factors, including genetics, diet, age, and toxicological agents like cigarette smoke, environmental contaminants, and drugs. The disruption of this balance, that is called dysbiosis, is associated with a plethora of diseases, including metabolic diseases, inflammatory bowel disease, chronic obstructive pulmonary disease, periodontitis, skin diseases, and neurological disorders. The importance of the host microbiome for the human health has also led to the emergence of novel therapeutic approaches focused on the intentional manipulation of the microbiota, either by restoring missing functions or eliminating harmful roles. In the present review, we outline recent studies devoted to elucidate not only the role of microbiome in health conditions and the possible link with various types of diseases but also the influence of various toxicological factors on the microbial composition and function.

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          An obesity-associated gut microbiome with increased capacity for energy harvest.

          The worldwide obesity epidemic is stimulating efforts to identify host and environmental factors that affect energy balance. Comparisons of the distal gut microbiota of genetically obese mice and their lean littermates, as well as those of obese and lean human volunteers have revealed that obesity is associated with changes in the relative abundance of the two dominant bacterial divisions, the Bacteroidetes and the Firmicutes. Here we demonstrate through metagenomic and biochemical analyses that these changes affect the metabolic potential of the mouse gut microbiota. Our results indicate that the obese microbiome has an increased capacity to harvest energy from the diet. Furthermore, this trait is transmissible: colonization of germ-free mice with an 'obese microbiota' results in a significantly greater increase in total body fat than colonization with a 'lean microbiota'. These results identify the gut microbiota as an additional contributing factor to the pathophysiology of obesity.
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            Is Open Access

            A human gut microbial gene catalogue established by metagenomic sequencing.

            To understand the impact of gut microbes on human health and well-being it is crucial to assess their genetic potential. Here we describe the Illumina-based metagenomic sequencing, assembly and characterization of 3.3 million non-redundant microbial genes, derived from 576.7 gigabases of sequence, from faecal samples of 124 European individuals. The gene set, approximately 150 times larger than the human gene complement, contains an overwhelming majority of the prevalent (more frequent) microbial genes of the cohort and probably includes a large proportion of the prevalent human intestinal microbial genes. The genes are largely shared among individuals of the cohort. Over 99% of the genes are bacterial, indicating that the entire cohort harbours between 1,000 and 1,150 prevalent bacterial species and each individual at least 160 such species, which are also largely shared. We define and describe the minimal gut metagenome and the minimal gut bacterial genome in terms of functions present in all individuals and most bacteria, respectively.
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              Cancer Statistics, 2008

              Each year, the American Cancer Society estimates the number of new cancer cases and deaths expected in the United States in the current year and compiles the most recent data on cancer incidence, mortality, and survival based on incidence data from the National Cancer Institute, Centers for Disease Control and Prevention, and the North American Association of Central Cancer Registries and mortality data from the National Center for Health Statistics. Incidence and death rates are age-standardized to the 2000 US standard million population. A total of 1,437,180 new cancer cases and 565,650 deaths from cancer are projected to occur in the United States in 2008. Notable trends in cancer incidence and mortality include stabilization of incidence rates for all cancer sites combined in men from 1995 through 2004 and in women from 1999 through 2004 and a continued decrease in the cancer death rate since 1990 in men and since 1991 in women. Overall cancer death rates in 2004 compared with 1990 in men and 1991 in women decreased by 18.4% and 10.5%, respectively, resulting in the avoidance of over a half million deaths from cancer during this time interval. This report also examines cancer incidence, mortality, and survival by site, sex, race/ethnicity, education, geographic area, and calendar year, as well as the proportionate contribution of selected sites to the overall trends. Although much progress has been made in reducing mortality rates, stabilizing incidence rates, and improving survival, cancer still accounts for more deaths than heart disease in persons under age 85 years. Further progress can be accelerated by supporting new discoveries and by applying existing cancer control knowledge across all segments of the population.
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                Author and article information

                Journal
                Toxicology Research and Application
                Toxicology Research and Application
                SAGE Publications
                2397-8473
                2397-8473
                January 01 2017
                December 10 2017
                January 01 2017
                : 1
                : 239784731774188
                Affiliations
                [1 ]PMI R&D, Philip Morris Products S.A., Neuchatel, Switzerland (Part of Philip Morris International group of companies)
                Article
                10.1177/2397847317741884
                9133237b-4669-4b15-964d-443c63a96da1
                © 2017

                http://journals.sagepub.com/page/policies/text-and-data-mining-license

                History

                Quantitative & Systems biology,Biophysics
                Quantitative & Systems biology, Biophysics

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