A review on gut microbiota: a central factor in the pathophysiology of obesity

Cunningham et al. Lipids in Health and Disease https://doi.org/10.1186/s12944-021-01491-z (2021) 20:65 REVIEW Open Access A review on gut microbiota: a central factor in the pathophysiology of obesity A. L. Cunningham1,2* , J. W. Stephens2 and D. A. Harris1,2 Abstract Obesity and its complications constitute a substantial burden. Considerable published research describes the novel relationships between obesity and gut microbiota communities. It is becoming evident that microbiota behave in a pivotal role in their ability to influence homeostatic mechanisms either to the benefit or detriment of host health, the extent of which is not fully understood. A greater understanding of the contribution of gut microbiota towards host pathophysiology is revealing new therapeutic avenues to tackle the global obesity epidemic. This review focuses on causal relationships and associations with obesity, proposed central mechanisms encouraging the development of obesity and promising prospective methods for microbiota manipulation. Keywords: Gut microbiota, Obesity, Metabolic syndrome, Faecal microbiota transplant Background The worldwide prevalence of obesity has approximately tripled since 1975 with a current estimate of 1.9 billion adults being classed as overweight (body mass index, BMI ≥ 25 kg/m2). This currently outnumbers those with malnutrition [1, 2]. Obesity is defined as the ‘abnormal or excessive fat accumulation that may impair health’ and is measured using the BMI [3]. Factors contributing towards the obesity epidemic include an increased accessibility to energy-dense foods, an increase in sedentary activity and the possible involvement of the gut microbiota on host metabolism. Although the fundamental cause of obesity is an energy imbalance between the calories consumed and the calories expended [1], body weight is not influenced by the calorific ingestion, but rather by the calories that are absorbed [4]. When adipose tissue exceeds its buffering capacity to store excess triglycerides, a resulting overflow of lipids into the systemic circulation occurs [5]. This lipid overspill to non-adipose tissues such as the liver, * Correspondence: 1 Department of Surgery, Swansea Bay University Health Board, Swansea SA2 8QA, UK 2 Swansea University Medical School, Swansea University, Swansea SA2 8QA, UK skeletal muscle and pancreas culminates in ectopic fat storage and the subsequent development of insulin resistance. Secondly, inflammation in adipose tissue increases, triggering the production and secretion of pro-inflammatory cytokines and adipokines, which contribute to the development of peripheral insulin resistance and altered glucose homeostasis [5]. Gut microbiota In the early 1900s, Élie Metchnikoff, a Russian-born zoologist and microbiologist first postulated the theory that gut microbiota behave as central modulators influencing host homeostasis and metabolism [6]. He believed that disruption of host homeostasis by particular bacteria increased the possibility of a disease state resulting in systemic toxicity from bacterial by-products [6]. An adult human is colonised by approximately 100 trillion microbes, most of which are predominantly found in the gastrointestinal tract (GIT), the largest population residing in the colon [7]. Scientists are gaining a greater understanding of the ‘normal’ bacterial communities and physiology of present gut microbiota through population research such as the Human Microbiome Project [8]. © The Author(s). 2021 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. Cunningham et al. Lipids in Health and Disease (2021) 20:65 Taxonomy is the study of classifying microbiota and provides a rigid structure for the arrangement of particular microbiota into groups on the basis of mutual similarity or evolutionary relatedness. In bacterial taxonomy the most commonly used ranks (levels) in ascending order are species, genera, families, orders, classes, phyla and domain [9]. The most abundant faecal bacterial groups of both lean and obese subjects are the phyla Firmicutes and Bacteroidetes [10, 11]. Approximately 90% of all phylotypes of gut bacteria belong to either the grampositive Firmicutes (64%) or the gram-negative Bacteroidetes (23%) [8, 12]. Other important phyla are Proteobacteria, Actinobacteria, Verrucomicrobia and Fusobacteria [8, 13–15]. The host genome is pivotal in controlling the composition of gut microbiota, however many external factors such as diet, illness, lifestyle, hygiene and the use of medications can contribute to changes in bacterial communities [16–18]. Growing evidence illustrates that dietary modification may be extremely influential in accounting for gut microbiota variations [17, 19, 20] (summarised in Fig. 1). Microbiota population differences in obesity Maintaining the heterogeneity and stability within the gut microbiota community is essential for promoting host health. Alterations in diversity and microbiota community structure may affect host metabolism resulting in obesity. Subjects with obesity have consistently demonstrated a reduction in diversity and Page 2 of 13 richness in microbial populations which can be reversed using weight loss interventions (diet low in fat and animal products, rich in fruit and vegetables) [21, 22]. Microbial diversity has been linked to the metabolic function of gut microbiota and low bacterial richness has been suggested to be a risk factor for obesity and low-grade inflammation [23, 24]. Obesity-related host microbiome display enrichment in particular gene categories involved in carbohydrate and lipid metabolism, and enzymes involved in glucose and insulin signaling pathways are downregulated [11, 21, 25]. Le Chatelier et al., analysed gene counts of a large cohort of obese and healthy subjects. Subjects identified with a low gene count (LGC) showed traits typical of an ‘obese phenotype’ associated with greater overall adiposity, insulin resistance and dyslipidaemia [26] (...truncated)