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      Fecal Transplants: What Is Being Transferred?

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      PLoS Biology
      Public Library of Science

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          Abstract

          Fecal transplants are increasingly utilized for treatment of recurrent infections (i.e., Clostridium difficile) in the human gut and as a general research tool for gain-of-function experiments (i.e., gavage of fecal pellets) in animal models. Changes observed in the recipient's biology are routinely attributed to bacterial cells in the donor feces (~10 11 per gram of human wet stool). Here, we examine the literature and summarize findings on the composition of fecal matter in order to raise cautiously the profile of its multipart nature. In addition to viable bacteria, which may make up a small fraction of total fecal matter, other components in unprocessed human feces include colonocytes (~10 7 per gram of wet stool), archaea (~10 8 per gram of wet stool), viruses (~10 8 per gram of wet stool), fungi (~10 6 per gram of wet stool), protists, and metabolites. Thus, while speculative at this point and contingent on the transplant procedure and study system, nonbacterial matter could contribute to changes in the recipient's biology. There is a cautious need for continued reductionism to separate out the effects and interactions of each component.

          Abstract

          Fecal transfers are increasingly common in animal models and humans. This essay notes that bacteria may not be the only player in donor feces that can affect the recipient's biology.

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          Fecal Microbiota Transplantation Induces Remission in Patients With Active Ulcerative Colitis in a Randomized Controlled Trial.

          Ulcerative colitis (UC) is difficult to treat, and standard therapy does not always induce remission. Fecal microbiota transplantation (FMT) is an alternative approach that induced remission in small series of patients with active UC. We investigated its safety and efficacy in a placebo-controlled randomized trial.
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            The epidemic of antibiotic-resistant infections: a call to action for the medical community from the Infectious Diseases Society of America.

            The ongoing explosion of antibiotic-resistant infections continues to plague global and US health care. Meanwhile, an equally alarming decline has occurred in the research and development of new antibiotics to deal with the threat. In response to this microbial "perfect storm," in 2001, the federal Interagency Task Force on Antimicrobial Resistance released the "Action Plan to Combat Antimicrobial Resistance; Part 1: Domestic" to strengthen the response in the United States. The Infectious Diseases Society of America (IDSA) followed in 2004 with its own report, "Bad Bugs, No Drugs: As Antibiotic Discovery Stagnates, A Public Health Crisis Brews," which proposed incentives to reinvigorate pharmaceutical investment in antibiotic research and development. The IDSA's subsequent lobbying efforts led to the introduction of promising legislation in the 109 th US Congress (January 2005-December 2006). Unfortunately, the legislation was not enacted. During the 110 th Congress, the IDSA has continued to work with congressional leaders on promising legislation to address antibiotic-resistant infection. Nevertheless, despite intensive public relations and lobbying efforts, it remains unclear whether sufficiently robust legislation will be enacted. In the meantime, microbes continue to become more resistant, the antibiotic pipeline continues to diminish, and the majority of the public remains unaware of this critical situation. The result of insufficient federal funding; insufficient surveillance, prevention, and control; insufficient research and development activities; misguided regulation of antibiotics in agriculture and, in particular, for food animals; and insufficient overall coordination of US (and international) efforts could mean a literal return to the preantibiotic era for many types of infections. If we are to address the antimicrobial resistance crisis, a concerted, grassroots effort led by the medical community will be required.
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              Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine.

              Growing empirical evidence suggests that nutrition and bacterial metabolites might impact the systemic immune response in the context of disease and autoimmunity. We report that long-chain fatty acids (LCFAs) enhanced differentiation and proliferation of T helper 1 (Th1) and/or Th17 cells and impaired their intestinal sequestration via p38-MAPK pathway. Alternatively, dietary short-chain FAs (SCFAs) expanded gut T regulatory (Treg) cells by suppression of the JNK1 and p38 pathway. We used experimental autoimmune encephalomyelitis (EAE) as a model of T cell-mediated autoimmunity to show that LCFAs consistently decreased SCFAs in the gut and exacerbated disease by expanding pathogenic Th1 and/or Th17 cell populations in the small intestine. Treatment with SCFAs ameliorated EAE and reduced axonal damage via long-lasting imprinting on lamina-propria-derived Treg cells. These data demonstrate a direct dietary impact on intestinal-specific, and subsequently central nervous system-specific, Th cell responses in autoimmunity, and thus might have therapeutic implications for autoimmune diseases such as multiple sclerosis.
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                Author and article information

                Journal
                PLoS Biol
                PLoS Biol
                plos
                plosbiol
                PLoS Biology
                Public Library of Science (San Francisco, CA USA )
                1544-9173
                1545-7885
                12 July 2016
                July 2016
                12 July 2016
                : 14
                : 7
                : e1002503
                Affiliations
                [1 ]Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee, United States of America
                [2 ]Department of Pathology, Microbiology, and Immunology, Vanderbilt University, Nashville, Tennessee, United States of America
                Author notes

                The authors have declared that no competing interests exist.

                Author information
                http://orcid.org/0000-0001-7346-0954
                Article
                PBIOLOGY-D-16-00865
                10.1371/journal.pbio.1002503
                4942072
                27404502
                fd37350f-b771-48e1-989d-00845ecb1028
                © 2016 Bojanova, Bordenstein

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                Page count
                Figures: 1, Tables: 0, Pages: 12
                Funding
                This work was supported by National Science Foundation Awards DEB 1046149 and IOS 1456778. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Essay
                Biology and Life Sciences
                Organisms
                Viruses
                Bacteriophages
                Biology and Life Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Medicine and Health Sciences
                Anatomy
                Digestive System
                Gastrointestinal Tract
                Biology and Life Sciences
                Organisms
                Bacteria
                Biology and Life Sciences
                Microbiology
                Archaean Biology
                Biology and Life Sciences
                Organisms
                Bacteria
                Gut Bacteria
                Clostridium Difficile
                Research and Analysis Methods
                Model Organisms
                Animal Models
                Mouse Models
                Research and Analysis Methods
                Model Organisms
                Animal Models
                Biology and Life Sciences
                Organisms
                Fungi

                Life sciences
                Life sciences

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