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Front. Biol.    2018, Vol. 13 Issue (5) : 327-341    https://doi.org/10.1007/s11515-018-1490-6
REVIEW
The journey of gut microbiome – An introduction and its influence on metabolic disorders
Ankita Chattopadhyay, Mythili S.()
School of Bio Sciences and Technology, VIT University, Vellore – 632014, Tamil Nadu, India
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Abstract

BACKGROUND: Metabolic disorders such as Obesity, Diabetes Type 2 (T2DM) and Inflammatory Bowel Diseases (IBD) are the most prevalent globally. Recently, there has been a surge in the evidence indicating the correlation between the intestinal microbiota and development of these metabolic conditions apart from predisposing genetic and epigenetic factors. Gut microbiome is pivotal in controlling the host metabolism and physiology. But imbalances in the microbiota patterns lead to these disorders via several pathways. Animal and human studies so far have concentrated mostly on metagenomics for the whole microbiome characterization to understand how microbiome supports health in general. However, the accurate mechanisms connecting the metabolic disorders and alterations in gut microbial composition in host and the metabolites employed by the microorganisms in regulating the metabolic disorders is still vague.

OBJECTIVE: The review delineates the latest findings about the role of gut microbiome to the pathophysiology of Obesity, IBD and Diabetes Mellitus. Here, we provide a brief introduction to the gut microbiome followed by the current therapeutic interventions in restoration of the disrupted intestinal microbiota.

METHODS: A methodical PubMed search was performed using keywords like “gut microbiome,” “obesity,” “diabetes,” “IBD,” and “metabolic syndromes.” All significant and latest publications up to January 2018 were accounted for the review.

RESULTS: Out of the 93 articles cited, 63 articles focused on the gut microbiota association to these disorders. The rest 18 literature outlines the therapeutic approaches in maintaining the gut homeostasis using probiotics, prebiotics and faecal microbial transplant (FMT).

CONCLUSION: Metabolic disorders have intricate etiology and thus a lucid understanding of the complex host-microbiome inter-relationships will open avenues to novel therapeutics for the diagnosis, prevention and treatment of the metabolic diseases.
Keywords gut microbiome      metabolic disorders      obesity      diabetes type 2      inflammatorybowel diseases      probiotics      prebiotics      FMT     
Corresponding Author(s): Mythili S.   
Online First Date: 20 August 2018    Issue Date: 25 October 2018
 Cite this article:   
Ankita Chattopadhyay,Mythili S.. The journey of gut microbiome – An introduction and its influence on metabolic disorders[J]. Front. Biol., 2018, 13(5): 327-341.
 URL:  
https://academic.hep.com.cn/fib/EN/10.1007/s11515-018-1490-6
https://academic.hep.com.cn/fib/EN/Y2018/V13/I5/327
Fig.1  Distribution of the gut microbiota in gastrointestinal tract of humans (Sartor, 2008) [Numbers in bracket shows microbial load per mL].
Fig.2  Mechanisms by which the gut microbiota produced SCFAs affect the host metabolism in lean and obese persons. {Adapted from Hartstra et al., 2015. Insights into the role of the microbiome in obesity and type-2 diabetes. Diabetes Care}.
Fig.3  Diagram representing the mechanisms by which the gut microbiota contributes to IBD pathophysiology.
Fig.4  Diagram depicting the role of prebiotics in modifying the gut microbiome and treatment of metabolic disorders. Prebiotics modify the intestinal microbiota by promoting the growth and activity of probiotics (E.g. Bifidobacterium spp.). This induces the differentiation of precursor cells into entero-endocrine L cells in the gut epithelium. L cells increase the secretion of GLP-1 and PYY in the portal plasma and decrease Ghrelin and plasma LPS levels. This activates the endocannabinoid system in the gut and adipose tissue. L cells also secrete GLP-2 that improves the distribution of tight junction proteins ZO-1 and Occludin, thereby alleviating endotoxemia, and localized inflammation. All these processes lead to decreased gut permeability, reduced hunger, enhanced satiety, reduction in body fat accumulation, increased insulin sensitivity and pancreatic beta cell mass, and normalized low-level inflammation, indicating the usefulness of prebiotics in management of Obesity, T2D and IBD.
Fig.5  Overview of the mechanisms of modulation of the intestinal microbiota against metabolic disorders by probiotics(Figure adapted from Le Barz et al., 2015). 1) Intake of Probiotics stimulates metabolites like SCFAs (Butyrate, Propionate, acetate etc.) which act as energy sources and regulate host metabolism. SCFAs bind to G-protein coupled receptors (GPR41/43) and secrete GLP-1 that inhibits glucagon secretion, reduce hepatic gluconeogenesis thereby enhancing glucose tolerance and insulin sensitivity. 2) Bile salt hydrolase activity in probiotics aid in detoxification of the bile salts and increase their survival in the gut. Bile salt de-conjugation decreases serum cholesterol and fatty acids and their absorption through the lumen causing decrease in lipid accumulation. 3) Probiotics activates AMPK pathway that elevates fatty acid oxidation, inhibits glycogen storage and decreases insulin resistance. ANGPTL4 is modulated by probiotics that restricts LPL production and prevents accumulation of fatty acids in adipocytes; this in turn prevents obesity and related disorders. 4) Probiotics promote TJ and AJ junction proteins production that reduces intestinal permeability and inhibits the influx of LPS into systemic circulation, thereby reducing metabolic endotoxemia. 5) Induces production of mucin proteins that assembles to form a mucus layer, acting as physical barrier against pathogen establishment. 6) Probiotics stimulates signaling pathways such as NF-kB and MAPK that recruits dendritic cells/macrophages and trigger anti-inflammatory pathways (Plasma cells multiplication and Treg cells). This results in decrease in pro-inflammatory cytokines and increase in anti-inflammatory cytokines and IgA immunoglobulins. (7) IgA mostly present in the mucus layer aid in maintaining the mucosal barrier. All these cause reduction in low-level inflammation and useful in colitis treatment. 8) Bacteriocin production by probiotics changes the gut microbial community and increases the commensal bacteria. It also prevents invasion by harmful microbes. Metabolites produced by the probiotics enhance the diversity of beneficial microbes and nutrients availability to be used by the surrounding colonocytes.
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