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      Probiotics in Extraintestinal Diseases: Current Trends and New Directions

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          Abstract

          Probiotics are defined as live microorganisms that when administered in adequate amounts confer a health benefit to the host. Their positive supplementation outcomes on several gastrointestinal disorders are well defined. Nevertheless, their actions are not limited to the gut, but may also impart their beneficial effects at distant sites and organs. In this regard, in this review article we: (i) comprehensively describe the main mechanisms of action of probiotics at distant sites, including bones, skin, and brain; (ii) critically present their therapeutic potential against bone, skin, and neuronal diseases (e.g., osteoporosis, non-healing wounds and autoimmune skin illnesses, mood, behavior, memory, and cognitive impairments); (iii) address the current gaps in the preclinical and clinical research; and (iv) indicate new research directions and suggest future investigations.

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          Low gut microbiota diversity in early infancy precedes asthma at school age.

          T. Abrahamsson, H. Jakobsson, A. Andersson … (2014)
          Low total diversity of the gut microbiota during the first year of life is associated with allergic diseases in infancy, but little is known how early microbial diversity is related to allergic disease later in school age. To assess microbial diversity and characterize the dominant bacteria in stool during the first year of life in relation to the prevalence of different allergic diseases in school age, such as asthma, allergic rhinoconjunctivitis (ARC) and eczema. The microbial diversity and composition was analysed with barcoded 16S rDNA 454 pyrosequencing in stool samples at 1 week, 1 month and 12 months of age in 47 infants which were subsequently assessed for allergic disease and skin prick test reactivity at 7 years of age (ClinicalTrials.gov ID NCT01285830). Children developing asthma (n = 8) had a lower diversity of the total microbiota than non-asthmatic children at 1 week (P = 0.04) and 1 month (P = 0.003) of age, whereas allergic rhinoconjunctivitis (n = 13), eczema (n = 12) and positive skin prick reactivity (n = 14) at 7 years of age did not associate with the gut microbiota diversity. Neither was asthma associated with the microbiota composition later in infancy (at 12 months). Children having IgE-associated eczema in infancy and subsequently developing asthma had lower microbial diversity than those that did not. There were no significant differences, however, in relative abundance of bacterial phyla and genera between children with or without allergic disease. Low total diversity of the gut microbiota during the first month of life was associated with asthma but not ARC in children at 7 years of age. Measures affecting microbial colonization of the infant during the first month of life may impact asthma development in childhood. © 2013 John Wiley & Sons Ltd.
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            Estrogen deficiency and bone loss: an inflammatory tale.

            M. Neale Weitzmann, Roberto Pacifici (2006)
            Estrogen plays a fundamental role in skeletal growth and bone homeostasis in both men and women. Although remarkable progress has been made in our understanding of how estrogen deficiency causes bone loss, the mechanisms involved have proven to be complex and multifaceted. Although estrogen is established to have direct effects on bone cells, recent animal studies have identified additional unexpected regulatory effects of estrogen centered at the level of the adaptive immune response. Furthermore, a potential role for reactive oxygen species has now been identified in both humans and animals. One major challenge is the integration of a multitude of redundant pathways and cytokines, each apparently capable of playing a relevant role, into a comprehensive model of postmenopausal osteoporosis. This Review presents our current understanding of the process of estrogen deficiency-mediated bone destruction and explores some recent findings and hypotheses to explain estrogen action in bone. Due to the inherent difficulties associated with human investigation, many of the lessons learned have been in animal models. Consequently, many of these principles await further validation in humans.
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              Short-chain fatty acids regulate systemic bone mass and protect from pathological bone loss

              Sébastien Lucas, Yasunori Omata, Jörg Hofmann … (2018)
              Microbial metabolites are known to modulate immune responses of the host. The main metabolites derived from microbial fermentation of dietary fibers in the intestine, short-chain fatty acids (SCFA), affect local and systemic immune functions. Here we show that SCFA are regulators of osteoclast metabolism and bone mass in vivo. Treatment of mice with SCFA as well as feeding with a high-fiber diet significantly increases bone mass and prevents postmenopausal and inflammation-induced bone loss. The protective effects of SCFA on bone mass are associated with inhibition of osteoclast differentiation and bone resorption in vitro and in vivo, while bone formation is not affected. Mechanistically, propionate (C3) and butyrate (C4) induce metabolic reprogramming of osteoclasts resulting in enhanced glycolysis at the expense of oxidative phosphorylation, thereby downregulating essential osteoclast genes such as TRAF6 and NFATc1. In summary, these data identify SCFA as potent regulators of osteoclast metabolism and bone homeostasis.
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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): 05 April 2019
                Publication date Collection: April 2019
                Volume: 11
                Issue: 4
                Electronic Location Identifier: 788
                Affiliations
                [1 ]Department of Molecular Biology and Genetics, Faculty of Health Sciences, Democritus University of Thrace, Alexandroupolis 68100, Greece; despkiou1@ 123456mbg.duth.gr (D.E.K.); a.karapetsas@ 123456dundee.ac.uk (A.K.); kyriakikarolidou@ 123456gmail.com (K.K.); apappa@ 123456mbg.duth.gr (A.P.)
                [2 ]Department of Applied Sciences, Northumbria University, Newcastle Upon Tyne NE1 8ST, UK; m.panagiotidis@ 123456northumbria.ac.uk
                Author notes
                [* ]Correspondence: agalanis@ 123456mbg.duth.gr ; Tel.: +30-25510-30634
                [†]

                Current address: MRC Protein Phosphorylation & Ubiquitylation Unit, University of Dundee, Sir James Black Centre, Dundee DD1 5EH, UK.

                Author information
                https://orcid.org/0000-0002-1450-3552
                https://orcid.org/0000-0001-9991-3173
                Article
                Publisher ID: nutrients-11-00788
                DOI: 10.3390/nu11040788
                PMC ID: 6521300
                PubMed ID: 30959761
                SO-VID: 19b891fe-f711-455d-b88f-cdcc3bb14133
                Copyright © © 2019 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 : 02 March 2019
                Date accepted : 02 April 2019
                Categories
                Subject: Review

                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: probiotics,gastrointestinal,skin,bone,neuronal disease,microbiota
                Data availability:
                ScienceOpen disciplines: Nutrition & Dietetics
                Keywords: probiotics, gastrointestinal, skin, bone, neuronal disease, microbiota

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