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Insights Into the Human Gut Microbiome - a Review Review Article Insights into The Human Gut Microbiome - A Review Balanehru Subramanian1,*, Sundarakrishnan Balakrishnan1, Krishna G. Seshadri2, Frederick A. Valeriote3 1Center for Animal Research, ABSTRACT Training and Service, (CAReTS), Central Inter-Disciplinary Various microbial communities and their genes collectively known as microbiome exist throughout the human body. The microbiome endows us with physiologic Research Facility, capacities that we have not had to evolve on our own and thus is both a manifestation 2 Department of Endocrinology, of who we are genetically and metabolically, and a reflection of our state of well- Diabetes and Metabolism, being. Our distal gut is the known ecosystem with highest density of microbial population and the most comprehensively surveyed to date. The gut microbiome is Mahatma Gandhi Medical a complex ecosystem that affects the development, immunological responses and College and Research nutritional status of the host. This review briefly discusses the significance of the gut Institute, Sri Balaji Vidyapeeth, microbiome in human health and wellness. (Deemed to be University), Keywords: Puducherry-607402. Microbiome, Gut, Health, Probiotics, Metagenomics 3 Josephine Ford Cancer Center, Division of Hematology, Oncology, Department of INTRODUCTION and disease are wide ranging, the study Internal Medicine, Henry Ford DNA is what makes us what we are, of humans and model animal systems Health System, Detroit, MI but many of us don’t realize that the with strong phenotypes is essential 48202, USA. DNA that defines us is not just that for making focus not only on bacteria, of our own human cells, but also that but also other microbes. The microbial of the millions of microbes living in/ composition is determined mostly by on the human body.1 There are over environmental factors with limited 100 trillion microorganisms residing input from host genetics.5 The principle in the human gut, including bacteria, of ancient associations between hosts fungi, algae, and protozoa, making and their microbial communities is up what are known as the “Human evident in the present day effects that For Correspondence Microbiome”. As Hippocrates quoted the gut microbiome exerts on host *Dr. Balanehru Subramanian, “Death sits in the bowels” and “bad biology, ranging from the structure Email: [email protected] digestion is the root of all evil”, it and functions of the gut and the Date of is known that health is incomplete innate and adaptive immune systems, Submisssion: 20-05-2018 without a healthy gut.2 DNA based to host energy metabolism.6,7 In this Acceptance: 18-07-2018 technologies expanded our knowledge review we address the significance of by generating adequate information gut microbiome in human health and on the composition and functional wellness. microbial communities. Human Microbiome Project (HMP) by the US IMPORTANCE OF MICROBIOME National Institutes of Health and the European project, MetaHIT pioneered Human Microbiome is essential for to answer fundamental questions like human biology as they facilitate Access this article online their function, composition, pathways the metabolism, produce essential Quick Response Code of microbes, biology and medical vitamins, confer protection against significance of the human microbiome invasion by opportunistic pathogens, and its collective genes.3 The gut plays a key role in maintaining tissue microbiome and its byproducts play homeostasis, as well as, required for a vital role in overall health and/or the development and differentiation disease depending on the strains of of the immune system.6,8 In addition microorganisms that predominate.4 to playing a critical role in human https://www.jbcahs.org As the implications for human health health, changes in microbiome SBV Journal of Basic, Clinical and Applied Health Science - Volume 2 | Issue 3 | July - September 2018 103 Balanehru Subramanian et al,: Insights into the human gut microbiome - A Review composition is associated with a number of human Mainly two gradients of microbial population are disease such as Crohn’s disease, chronic periodontitis, found in the gut. First, microbial density increases inflammatory bowel disease, irritable bowel syndrome, from proximal to the distal gut: stomach contains tropical enteropathy, antibiotic-associated diarrhea, 101 microbial cells/gram, duodenum 103 cells/gram, and bacterial vaginosis. For each disease a microbial jejunum 104 cells/gram, ileum 107 cells/gram and colon community has been proposed, leading to stereotypic up to 1012 cells/gram and along the tissue lumen axis interactions between community members associated with few bacteria adhering to the tissue or mucus but with some of these pathologies.3,9,10 a large number being present in the lumen. Second, bacterial diversity increases in the same axes and manner 2 DIVERSITY IN GUT MICROBIOME as microbial density. Many bacterial species are present in the lumen, whereas fewer, but well adapted species, A human harbors a population of ~1014 bacterial cells, including several proteobacteria and Akkermansia the composition of which varies by anatomical site muciniphila, adhere and reside within the mucus layer such as skin, mucosal surfaces and intestinal lumen. close to the tissue.18 In fact, the metabolic activity of Each area consists of certain families and genera, the gut microbiome equals that of the liver, and the which can be of a unique, fingerprint.11,12 These intestinal microbiome can therefore be considered as characteristics indicate that mankind has co-evolved an additional organ.16 with their microbial partners. The microbiome in the colon is the most biodiverse ecosystem in the Next generation sequencing-based approaches human body 13,14 representing more than 70% of all have detected an impressive biodiversity at lower microbes in the body. Colon is the largest organ with phylogenetic levels with up to1000 different species majority of microbial colonization. The normal gut among people, and each subject harbors a very unique microbiome is predominated by anaerobic bacteria, subset of microorganisms. The total genome of these which outnumber the aerobic and facultative bacteria microorganisms provides the host with essential by thousand fold. Indeed, out of the 100 different functional traits that human beings have not evolved bacterial phyla detected on our planet, only seven on their own.19 For instance, the carbohydrate-active are found in human gut – Firmicutes, Bacteroidetes, enzymes encoded in the microbial glycobiome allow Actinobacteria, Proteobacteria, Verrucomicrobia, the host to extract energy from otherwise indigestible Tenericutes, and Fusobacteria15 – of which Firmicutes polysaccharides,20 complementing the poor human and Bacteroidetes represent together up to 90% of glycobiome diversity.21 the ecosystem16. (Figure 1) Altogether, the human microbiome is similar to that of other mammals at the Various factors such as mother’s microbiome, phylum level, but most bacterial families and genera mode of delivery, feeding type, the environment, seem to be distinct.17 including weaning and use of antibiotics influences gut Figure 1 : Major bacterial Phyla and their diversity in the human gut microbiome. 104 SBV Journal of Basic, Clinical and Applied Health Science - Volume 2 | Issue 3 | July - September 2018 Balanehru Subramanian et al,: Insights into the human gut microbiome - A Review microbiome among individuals. Babies microbiome, in culture. Gram staining was the earlier technique born through C-section, showed similar skin microbial that was used to broadly identify the physiological communities of mothers, whereas vaginally delivered character of the microbial community but lacked lower infants acquired bacterial communities resembling taxonomic levels.28 As the culture based approaches led the vaginal microbiome of their mothers.22 Scientists to bias, isolation of full diversity of microorganisms believe that microbiome-fetus-in utero relationships remained largely underexplored. The uncultivable co-exists even before birth determining the course of microbes identified by the DNA based methods lead pregnancy and development of the fetus.23 The neonate to identification of taxonomic diversity of the microbial gut is dominated by bifidobacteria, especially in milk community at a broad level and detect the presence fed infants. Genome analysis of Bifidobacterium longum or absence of individual biochemical functions.29 subsp. infantis revealed that feeding pattern like breast Fluorescent in situ hybridization (FISH) was the one milk or formula, determined the types of bifidobacteria of the earliest targeted metagenomic assays to study found. Breast fed infants have high composition of the unculturable microbial community from species Bifidobacterium breve, formula fed infants lacked B. breve to taxonomy. but contained Bifidobacteria longum. Infants fed with breast milk and later a prebiotic formula consisting of Nevertheless, DNA sequencing of cloned libraries standard formula milk containing a mixture of specific are expensive and laborious. High-throughput DNA galacto and fructo oligosaccharides, has a Bifidobacteria sequencing in combination with genome-scale platforms breve fecal population.24 such as proteomics or metabolomics are currently used to study microbiome. With the advent of bacterial Compared to early stages of a human life, phylogeny, based on the small-subunit 16S ribosomal microbiome composition undergoes significant changes RNA (rRNA) sequence, the
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