ARTICLE Gut microbiota: Its role in diabetes and obesity Neil Munro Citation: Munro N (2016) Gut The gut microbiota is a community of microogranisms that live in the gut and intestinal microbiota: Its role in diabetes tract. The microbiota consists of bacteria, archaea and eukarya, as well as viruses, but is and obesity. Diabetes & Primary Care 18: 168–73 predominantly populated by anaerobic bacteria. Relationships between gut microbiota constituents and a wide range of human conditions such as enterocolitis, rheumatoid Article points arthritis, some cancers, type 1 and type 2 diabetes, and obesity have been postulated. 1. The role of the gut microbiota This article covers the essentials of the gut microbiota as well as the evidence for its role in certain disease progressions in diabetes and obesity. has been postulated, particularly its role in diabetes and obesity. he human gut microbiota is “an ecological Identifying microbiota constituents 2. There is much greater community of commensal, symbiotic and Until relatively recently, bacteria could only be genetic diversity between pathogenic micro-organisms that literally identified by direct microscopy and culture. people’s gut microbiota than T share our body space” (Lederberg and McCray, This proved particularly problematic with most between their genomes. 2001). It is made up of between 10 and 100 trillion anaerobic commensal gut flora (Ursell et al, 3. Improved understanding of the mechanisms by which the micro-organisms (with a mass weight of 1.5 kg) 2012). It has only been in recent years that human microbiota contributes and is found in the distal intestine (Allin et al, advances in gene sequencing and analytical to the development of 2015). The microbial community acts in concert techniques have made it possible to define and type 1 and type 2 diabetes with the body to provide important functions classify microbial DNA from faecal collections offers the potential for novel interventions. that the body cannot provide alone. The gut – generally considered to reflect the distal bowel microbiota is involved in the following: microbiota (Kuczynski et al, 2012). Two detection Key words l It is a key component of the immune system. methods are currently employed; targeted 16S – Bacteria l Protection against pathogens. ribosomal RNA gene sequencing and un-targeted – Gut l Regulation of intestinal hormone secretion. whole-genome shotgun sequencing (otherwise – Microbiota l Modulation of gastrointestinal nerve known as metagenomic sequencing; Weinstock, function. 2012). The former generates information about l Synthesis of vitamin K, folate and B12. the bacteria themselves (i.e. types, numbers and l Generation of short-chain fatty acids through relationships), while the latter provides a picture of fermentation of non-digestible carbohydrates. the collective genome of the gut microbiota (i.e. the l The breakdown of toxins and medications. gut microbiome). Gene diversity in the human microbiome Interest in the association between constituent dwarfs that of the entire human genome. The elements of the human microbiota and disease MetaHIT Consortium found 3.3 million non- dates back to the 1680s around the time of the redundant genes in the microbiome compared to birth of the study of microbiology itself (Dobell, 22 000 genes in the human genome (Qin et al, 1920). In his research into the diversity of the 2010). More recently a microbial gene catalogue human microbiota, Antonie van Leeuwenhoek of 9.9 million genes from European, Chinese and (1684) compared his own oral and faecal American samples has been published (Li et al, microbiota and noticed significant differences 2014). Importantly, the genetic diversity of the Author in microbes between these different sources. He microbiome between individuals is far greater Neil Munro is Visiting Professor went on to examine and compare microbiota than that of the human genome. People are 99.9% in Primary Care Diabetes, from others in good health, as well as those identical to each other in terms of their human Department of Clinical and Experimental Medicine, with established disease, also noting significant genome but can be 80–90% different from each University of Surrey. differences between sample sites. other in terms of their gut microbiome (Turnbaugh 168 Diabetes & Primary Care Vol 18 No 4 2016 Gut microbiota: Its role in diabetes and obesity et al, 2009). In an age of personalised medicine, age when immune-related changes in the gut Page points the variation within the microbiome presents a microbiota can occur (Arumugam et al, 2011). 1. In an age of personalised potentially useful avenue for future interventions medicine, the variation in disease processes. What is the relationship between the within the microbiome from person to person presents a microbiota and diabetes? potentially useful avenue for Does the microbiota change throughout Relationships between gut microbiota constituents future interventions in disease life? and human conditions, including enterocolitis, processes. Birth and childhood rheumatoid arthritis, muscular dystrophy, multiple 2. The microbiota and its bacterial composition is influenced by The relative bacterial composition of the microbiota sclerosis, some cancers and a range of psychiatric several factors throughout life. is influenced by several factors throughout life and disorders, have been postulated. Of key interest to There are variations from birth in childhood in particular. the endocrine world is the possible link with type 1 to adulthood. Babies delivered vaginally develop microbial diabetes, type 2 diabetes and obesity. 3. The mechanisms through which the microbiota may precipitate populations within 20 minutes of birth, mirroring type 1 diabetes in susceptible those of their mother’s vagina and rectum What is the relationship between the individuals relate to alterations (Lactobacillus, Prevotella or Sneathia), while the microbiota and type 1 diabetes? in intestinal permeability and microbiota of babies born by Caesarian section are The involvement of the microbiota in the modification of intestinal immunity. derived from microbes on the hands that touch development of type 1 diabetes in animals was first and hold the baby after birth (Staphylococcus, proposed in 1987 by Suzuki et al. A recent Finnish Corynebacterium and Propionibacterium; human study used age and HLA-DQ genotype to Domininguez-Bello et al, 2010). match four children who went on to develop type 1 The gut microbiota of infants tends to be diabetes with four children who remained healthy. narrow and unstable. Breast feeding, formula Comparison of their microbiomes revealed a lesser milk, antibiotic treatment, illness and travel can diversity and stability of faecal microbiota in the all contribute to the changeable milieu of the first year of life in children in the former group microbiota in the young (Koenig et al, 2011). After (Giongo et al, 2011). The children who developed the age of 3 years, diet, including variations in solid type 1 diabetes were subsequently found to have food ingestion, and illness are the predominant a decreased ratio of Firmicutes versus Bacteroidetes determinants of the microbiota (Power et al, 2014). (de Goffau et al, 2013). Other studies have also By the age of 7 years, Firmucites and Bacteroidetes reported a greater proportion of Bacteroidetes in comprise about 90% of the microorganisms islet body-positive children than in auto-antibody- present in a child’s microbiota, with the remaining negative children (de Goffau et al, 2014). 10% being made up by Tericutes, Cyanocobacteria The mechanisms through which the microbiota and Proteobacteria. The microbiota becomes more may precipitate type 1 diabetes in susceptible stable at this stage and begins to resemble that of individuals relate to alterations in intestinal adults (Dominguez-Bello et al, 2011). permeability and modification of intestinal immunity. In the healthy state, the intestinal Adulthood epithelium prevents food antigens, as well as In healthy adults, the microbiota is stable and is commensal and pathogenic bacteria, from inducing related to long-term diet patterns. Three enterotypes systemic immune responses (Mazmanian et al, are found in adults globally: Bacteroides (the 2005). predominant class in the phylum Bacteroidetes), In type 1 diabetes, the development of a more Prevotella and Ruminococcus (Wu et al, 2011). All permeable intestinal barrier (a key component of three can be linked to diet and living conditions. For human defence mechanisms) may be attributable instance, Bacteroides are found in those with high to metabolites of gut microbiota, as much as animal protein and saturated fat intake (western to any direct action of microbes themselves. diet), while Prevotella, by contrast, are found in Children with type 1 diabetes have low numbers those in agricultural and vegetarian communities of Bifidobacteria, which are lactate-producing where high consumption of carbohydrates and microorganisms (de Goffau et al, 2013). Butyrate, sugars is the norm, and remain so until older a short-chain fatty acid, is derived from lactate and Diabetes & Primary Care Vol 18 No 4 2016 169 Nutrients 2015, 7, page–page 5. Microbiota: Molecular Mechanisms in T1D To explain the pathways and the impact of T1D‐associated dysbiosis in the metabolism, it is necessary to study the microbiota structural dynamics as an integral organ [52]. Understanding that the gut microbiota is an organ will make it possible to integrate its relationship with