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      Gut Microbiota as a Target for Preventive and Therapeutic Intervention against Food Allergy

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          Abstract

          The gut microbiota plays a pivotal role in immune system development and function. Modification in the gut microbiota composition (dysbiosis) early in life is a critical factor affecting the development of food allergy. Many environmental factors including caesarean delivery, lack of breast milk, drugs, antiseptic agents, and a low-fiber/high-fat diet can induce gut microbiota dysbiosis, and have been associated with the occurrence of food allergy. New technologies and experimental tools have provided information regarding the importance of select bacteria on immune tolerance mechanisms. Short-chain fatty acids are crucial metabolic products of gut microbiota responsible for many protective effects against food allergy. These compounds are involved in epigenetic regulation of the immune system. These evidences provide a foundation for developing innovative strategies to prevent and treat food allergy. Here, we present an overview on the potential role of gut microbiota as the target of intervention against food allergy.

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          An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system.

          Sarkis Mazmanian, Cui Hua Liu, Arthur O Tzianabos … (2005)
          The mammalian gastrointestinal tract harbors a complex ecosystem consisting of countless bacteria in homeostasis with the host immune system. Shaped by evolution, this partnership has potential for symbiotic benefit. However, the identities of bacterial molecules mediating symbiosis remain undefined. Here we show that, during colonization of animals with the ubiquitous gut microorganism Bacteroides fragilis, a bacterial polysaccharide (PSA) directs the cellular and physical maturation of the developing immune system. Comparison with germ-free animals reveals that the immunomodulatory activities of PSA during B. fragilis colonization include correcting systemic T cell deficiencies and T(H)1/T(H)2 imbalances and directing lymphoid organogenesis. A PSA mutant of B. fragilis does not restore these immunologic functions. PSA presented by intestinal dendritic cells activates CD4+ T cells and elicits appropriate cytokine production. These findings provide a molecular basis for host-bacterial symbiosis and reveal the archetypal molecule of commensal bacteria that mediates development of the host immune system.
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            Relating the metatranscriptome and metagenome of the human gut.

            Eric Franzosa, Xochitl C Morgan, Nicola Segata … (2014)
            Although the composition of the human microbiome is now well-studied, the microbiota's >8 million genes and their regulation remain largely uncharacterized. This knowledge gap is in part because of the difficulty of acquiring large numbers of samples amenable to functional studies of the microbiota. We conducted what is, to our knowledge, one of the first human microbiome studies in a well-phenotyped prospective cohort incorporating taxonomic, metagenomic, and metatranscriptomic profiling at multiple body sites using self-collected samples. Stool and saliva were provided by eight healthy subjects, with the former preserved by three different methods (freezing, ethanol, and RNAlater) to validate self-collection. Within-subject microbial species, gene, and transcript abundances were highly concordant across sampling methods, with only a small fraction of transcripts (<5%) displaying between-method variation. Next, we investigated relationships between the oral and gut microbial communities, identifying a subset of abundant oral microbes that routinely survive transit to the gut, but with minimal transcriptional activity there. Finally, systematic comparison of the gut metagenome and metatranscriptome revealed that a substantial fraction (41%) of microbial transcripts were not differentially regulated relative to their genomic abundances. Of the remainder, consistently underexpressed pathways included sporulation and amino acid biosynthesis, whereas up-regulated pathways included ribosome biogenesis and methanogenesis. Across subjects, metatranscriptional profiles were significantly more individualized than DNA-level functional profiles, but less variable than microbial composition, indicative of subject-specific whole-community regulation. The results thus detail relationships between community genomic potential and gene expression in the gut, and establish the feasibility of metatranscriptomic investigations in subject-collected and shipped samples.
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              Commensal bacteria protect against food allergen sensitization.

              A Stefka, T. Feehley, P. Tripathi … (2014)
              Environmentally induced alterations in the commensal microbiota have been implicated in the increasing prevalence of food allergy. We show here that sensitization to a food allergen is increased in mice that have been treated with antibiotics or are devoid of a commensal microbiota. By selectively colonizing gnotobiotic mice, we demonstrate that the allergy-protective capacity is conferred by a Clostridia-containing microbiota. Microarray analysis of intestinal epithelial cells from gnotobiotic mice revealed a previously unidentified mechanism by which Clostridia regulate innate lymphoid cell function and intestinal epithelial permeability to protect against allergen sensitization. Our findings will inform the development of novel approaches to prevent or treat food allergy based on modulating the composition of the intestinal microbiota.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Nutrients
                Journal ID (iso-abbrev): Nutrients
                Journal ID (publisher-id): nutrients
                Title: Nutrients
                Publisher: MDPI
                ISSN (Electronic): 2072-6643
                Publication date (Electronic): 28 June 2017
                Publication date Collection: July 2017
                Volume: 9
                Issue: 7
                Electronic Location Identifier: 672
                Affiliations
                [1 ]Department of Translational Medical Science-Pediatric Section, University of Naples “Federico II”, 80131 Naples, Italy; aitoro.rosita@ 123456gmail.com (R.A.); paparolorella@ 123456gmail.com (L.P.); antonioamoroso87@ 123456gmail.com (A.A.); mara.dicostanzo@ 123456live.it (M.D.C.); lindacosenza@ 123456libero.it (L.C.); vivianagranata@ 123456gmail.com (V.G.); carmendiscala@ 123456gmail.com (C.D.S.); ritanocerino@ 123456alice.it (R.N.); giovanna.trinchese@ 123456unina.it (G.T.); mariangelamontella@ 123456libero.it (M.M.)
                [2 ]Department of Agricultural Sciences, Division of Microbiology, University of Naples “Federico II”, 80055 Portici, Italy; ercolini@ 123456unina.it
                [3 ]Task Force on Microbiome Studies, University of Naples “Federico II”, 80131 Naples, Italy
                [4 ]European Laboratory for the Investigation of Food Induced Diseases, University of Naples “Federico II”, 80131 Naples, Italy
                [5 ]CEINGE Advanced Biotechnologies, University of Naples “Federico II”, 80131 Naples, Italy
                Author notes
                [* ]Correspondence: berni@ 123456unina.it ; Tel.: +39-081-746-2680
                Article
                Publisher ID: nutrients-09-00672
                DOI: 10.3390/nu9070672
                PMC ID: 5537787
                PubMed ID: 28657607
                SO-VID: 550db29e-e4fc-4d12-8220-0c828d074ad5
                Copyright © © 2017 by the authors.
                License:

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                Date received : 23 March 2017
                Date accepted : 23 June 2017
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: cow’s milk allergy,diet,immune tolerance,dysbiosis,probiotics,short chain fatty acids,butyrate
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: cow’s milk allergy, diet, immune tolerance, dysbiosis, probiotics, short chain fatty acids, butyrate

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