Engineering the Gut Microbiome for Treatment of Obesity: A Review of Current Understanding and Progress

Abstract

Obesity is a complex, multifactorial disease that is increasing in prevalence despite extensive research and efforts to curb it. Over the last decade, gut microbiome has emerged as an important contributor to the pathogenesis of obesity. Microbiome profile is altered in obese phenotype and the causative role of microbiome in obesity is demonstrated in fecal microbiota transplantation studies. Herein, recent evidences supporting the role of gut microbiome in obesity and the current therapies designed to engineer gut microbiome for treatment of obesity will be reviewed. The microbial enterotypes associated with obesity is outlined, and the gut microbiota-driven metabolism and low-grade inflammation linking gut microbiome and obesity is examined. How the different intrinsic and extrinsic factors such as host genetics, mode of childbirth delivery, diet, lifestyle habits and use of antibiotics influence the composition of the gut microbiome in the development of obesity is evaluated. Also, the efficacy of current microbiome-based therapies in the forms of prebiotics, probiotics and engineered microbes that are used to manipulate gut microbiome in treating obesity is discussed. 1. Gut Microbiome in Obesity The worldwide prevalence of obesity (Body mass index, BMI ≥30 kg m −2) increased from 3.2% to 10.8% in men and from 6.4% to 14.9% in women over the last 4 decades. [1] Obesity is a complex disease that is caused by multiple factors, namely genetics, excessive caloric intake, sedentary lifestyle, socioeconomic status, poor sleep quality, parental weight, and the environment. [2] Obesity increases the risk of many diseases,

Comprehensive functional core microbiome comparison in genetically obese and lean hosts under the same environment

“…We also observed an increase in the abundance of 4 MGs involved in the biosynthesis of peptidoglycans in the obese line: erfK, pbp2A , and mpl (0.63–0.42 SD, P 0 ≥ 0.97), and ftsI with lower evidence (0.12 SD, P 0 = 0.71). Bacterial lipopolysaccharides and peptidoglycans are microbiota-derived endotoxins mainly found in Gram-negative bacteria 30 , 67 contributing to metabolic endotoxemia 25 , 26 and fat-mass development 18 , 22 , 23 , 26 by boosting intestinal permeability 26 , 41 , 68 , 69 and triggering proinflammatory responses when binding CD 14 , TLR 4 27 (lipopolysaccharides), and NOD 1 and NOD 2 12 , 28 – 30 (peptidoglycans) host receptors. Besides, obese line harbored an increased abundance of 2 MGs involved in the metabolism of lipoproteins: apolipoprotein N-acyltransferase lnt and lipoprotein ygeR (0.41 and −0.38 SD, P 0 ≥ 0.95).…”

“…Bäckhed et al 16 were the first to report a striking difference in body-fat content observed between germ-free mice and conventionally raised mice, with the latter having 40% higher body-fat content 16 . After that, several studies have established that microbial pathways can contribute to obesity by altering apetite 24 , energy extraction from ingesta 17 – 23 , and inflammation and immunity processes via an increased production of microbial-derived metabolites 12 , 18 , 21 – 23 , 25 – 30 . At the same time, the gut microbiome composition is partially determined by the genes of the host 31 , 32 , as for example, host genes regulating the pH and redox conditions, motility of the intestinal tract, immune response, or the presence of receptors responding to metabolites with microbial origin 33 – 38 .…”

Gut Microbiota: The Missing Link Between Helicobacter pylori Infection and Metabolic Disorders?

“…The production of these metabolites, the integrity of gut mucosa and consequently the actions that gut bacteria would exert as a whole, would depend on the abundance and proportion of each bacterial taxa inhabiting our intestine. Determinants of gut microbiota composition include dietary intake or antibiotic treatment, among other exogenous and endogenous factors (20,30,135,136). Disruption of the gut bacterial equilibrium results in the deregulation of host metabolic functions and triggers the onset of obesity and obesity-related metabolic diseases (100,112).…”

Are Faecal Microbiota Analyses on Species-Level Suitable Clinical Biomarkers? A Pilot Study in Subjects with Morbid Obesity

“…Studies with various methods have shown associations between obesity and the gut microbiota, but not valid and congruent characteristics of the abnormal faecal microbiota (dysbiosis) [2,3,5]. Attempts to restore a normal bacterial composition for the prevention or treatment of obesity have not so far reached established clinical practice [5,6]. Irritable bowel syndrome (IBS), a common comorbidity in subjects with obesity, has also been associated with faecal dysbiosis [7][8][9].…”