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Potential Impacts of Gut Microbiota on Immune System Related Diseases: Current Studies and Future Challenges

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Potential Impacts of Gut Microbiota on Immune System Related Diseases: Current Studies and Future Challenges Acta Medica 2018; 49(2): 31-37 acta medica REVIEW Potential Impacts of Gut Microbiota on Immune System Related Diseases: Current Studies and Future Challenges 1 Tayfun Hilmi Akbaba , [BSc] ABSTRACT Banu Balcı Peynircioğlu *, [MD] Human microbiota includes trillions of cohabitant microorganisms in a symbiotic re- lationship. They directly or indirectly communicate with immune system. Human microbiome profiling studies has accelerated microbiota studies and interest to mi- 1, Hacettepe University, Faculty of Medicine, crobiota and disease relationship . Some metabolic activities of human microbiota Department of Medical Biology, Ankara, Turkey were known, but in recent years many different roles in addition to metabolic activi- ties, have been shown. It can affect systems and mechanisms, and most importantly clinical course of diseases in dysbiosis condition, and reduces most symptoms when * Corresponding Author: Banu Balci- Peynircioğlu. symbiosis is provided. These features make microbiota a potential therapeutic tool or [MD] Hacettepe University Faculty of Medicine, biomarker for a spate of disease in clinic applications.This review summarizes host- Department of Medical Biology, Ankara – Turkey gut microbiota interaction, role of microbiota in immune-related diseases, and poten- e-mail: [email protected] tial therapeutic approaches. Phone: +903122102541 Keywords: Gut microbiota, microbiome, immune system related disease Received: 11 April 2018, Accepted: 29 May 2018, Published online: 29 June 2018 INTRODUCTION The human microbiota consists of bacteria, archaea, of highly conserved sequence, and taxonomic pro- viruses and eukaryotic microbes that live in and on files, whole genome shogun (WGS) or metagenom- our bodies, and corporate genome of our micro- ics sequencing of whole community DNA, which bial symbionts, commensal and pathobiont (po- make easy to study microbiome. Also, reference tential pathogenic microbes) are called as microbi- microbial genome from human body is formed by ome [1]. Population of diverse microbial species on HMP. In addition to HMP, the MetaHIT project used or in human body is about one-tenth of the num- WGS data in order to examine the gut microbiome ber of human cells [2]. Their total genes are more in a cohort with different health status and physi- than 100 times that our own genes, and they have ological characteristics [6-7]. Optimized sequenc- more diverse genomic capacity than their host [3- ing protocols, increased knowledge of taxonomic 4]. Therefore, these microbes have enormous pos- classification, ability to form operational taxonom- sibility to affect our physiological conditions in the ic unit (OTU)-based community structure decreased case of both health and disease. They have crit- bias generated by these studies. Therefore, in order ic roles on metabolic functions, protection against to understand host-microbiota interactions and to pathogens, and education of our immune system. explain potential impact of microbiota on disease, Also, our physiological capacities are influenced by interest to microbiome researches has increased in- these essential functions straightforwardly or indi- crementally [4] (Figure 1). According to HMP data, rectly [5]. Increase in knowledge of advance mo- working on soft tissue (mid vagina, anterior nares, lecular biology and recent technological advance- and throat) and saliva is challenging because of ments for performing culture-independent analy- higher human genome contamination, while study- sis help to show great progress in microbiome re- ing gut microbiome is more preferable due to a rel- searches (Figure 1). The Human Microbiome Project atively low abundance of human reads (up to 1%) in (HMP) several complementary analyses such as 16S total reads. rRNA gene sequence (16S), gene including regions Immune system and gut microbiota relationship © 2018 Acta Medica. All rights reserved. 31 is one of the well-studied area among microbi- been trying to explore. In this review, we highlight- ome studies, however the effects of microbiota ed researches on relationship between microbiota or dysbiosis (microbiotic changes in systems and and immune diseases mainly inflammatory condi- host’s negative response to these change) on im- tions. Moreover, we discussed current and potential mune-related and auto inflammatory diseases has therapeutic approaches Figure 1. Number of publications on microbiome and gut microbiome from 2003 to 2017. Factors affecting gut microbiota Gut microbiota is not a stable organ which is affected by adult gut microbiota diversity in the way of increase in the a lot of factors result in deviation from core gut micro- abundance of anaerobic Firmicutes [9-10]. In the healthy biome (Figure 2). The microbial composition of the gas- state, Firmicutes, Bacteroidetes and Actinobacteria are trointestinal tract in humans shows noteworthy changes dominant bacterial phyla in post weaned children and through the lifespan (Figure 3). During childbirth the gas- adults [9-11]. Aging also changes the microbiota compo- trointestinal tract of infants is seen to be sterile. However, sition of gut. Numbers of facultative anaerobes show in- during or following birth, microbiota forms quickly by creasing trend, on the other hand, gram-negative bacte- bacteria transferred from mother. Infant feeding meth- ria (mainly Enterobacter) and number of good bacteria od and mode of delivery shape the microbiota in infants. like Lactobacilli and Bifidobacteria show decreasing trend Breast fed babies sustained children have a tendency to with age [12-13]. In addition to age, diet and lifestyle, host basically support Bifidobacteria in their gastrointestinal genetics, environmental contact, infection, pharmaceuti- tract while those of bottle-fed babies have a more various cals, hygiene conditions, relationship between microbio- bacteria population [8]. Transition to solid food helps to ta and immune system, even geography cause variation of increase microbial composition of the gut of infants like gut microbiota (Figure2) [9-10]. Figure 2. Factors affecting gut microbiota composition. 32 © 2018 Acta Medica. All rights reserved. Acta Medica 2018; 49(2): 31-37 Akbaba et al. Figure 3. Formation and alteration of microbiota during lifespan. Metabolic activities of gut microbiota Gut microbiota have functional activities like food me- from indigestable food components. These SCFAs vary tabolism, xenobiotics and drug metabolism, anti-mi- but most abundant ones are butyrate, acetate and pro- crobial protection and immunomodulation. First of all, pionate in gut. These SCFAs lower cholesterol level and symbiont bacteria and pathobiont bacteria live togeth- control blood glucose level since they are important for er in gut and some simbiont bacteria degrade indi- energy metabolism. Cholesterol homeostasis in the pe- gestable fibers which human digestive system do not. ripheral tissue is controlled by acetate and propionate Xylosglucan, a type of high branched plant fiber, can be which are substrates for gluconeogenesis in the liver. On converted to xylose which can be absorbed by epitheli- the other hand, colonocytes use butyrate, a mediator of al cells with the help of rare Bacteroides strain [14]. This cell proliferation as an energy source [15,16]. example also indicates how our gut microbiota and hu- man forms are in a mutual relationship. Gut microbiota is capable of production of short chain fatty acids (SCFAs) Figure 4. Roles of microbiota in the gut. © 2018 Acta Medica. All rights reserved. 33 Crosstalk between Gut Microbiota and Immune System Khachatryan and his group did microbiome research on Gut microbiota undertake an essential role in the matura- 19 FMF patients and 8 healthy individuals by sequenc- tion and devolopment of adaptive and innate immune sys- ing 16S rDNA and by doing specific probe based fluores- tem. Symbiont bacteria convert diet fibers to fucose which cence in situ hybridization (FISH) analysis. During attack is important for regulation of virulence factor [17]. Healthy period of FMF patients, total number of bacteria, and its gut epitelium surrounded by a layer composed of mu- diversity decreased significantly and major shifts in bac- cin glycoproteins that are secreted by the intestinal gob- terial populations within the Bacteroidetes, Firmicutes let cells. Mucus layer can be extended up to 150 μm away and Proteobacteria phyla. In remission period, gut bac- from the colonic epithelium. Signals coming from bacte- terial diversity with some deviations was close to the ria in gut lumen promote cells to make mucus synthesis, control group [30]. Therefore, MEFV mutations changes important for epithelial barrier function [18-19]. Genetic host-microbiota interactions and diversity of gut micro- deletion in mucin 2 gene causes colitis, which shows the biota in different periods of the disease. important role of mucus production stability of physical barrier of gut [20]. In addition to mucin proteins, to main- Inflammatory bowel disease (IBD) tain barrier integrity, goblet cells also produce resistin-like Inflammatory bowel disease (IBD), including Crohn’s dis- molecule-β (RELM-β) [21] . Interleukin-22(IL-22) induc- ease and ulcerative colitis, is characterized by chron- es the production of the antimicrobial peptides, such as ic relapsing intestinal inflammation with increasing in- REGIIIβ and REGIIIγ, from intestinal epithelial cells, which is cidence worldwide. Etiology of IBD remains largely un- a critical role on defensing against pathogens.
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