Gut Microbiota and Obesity | Catherine Graham, Kevin Whelan & Anne Mullen, Diabetes and Nutritional Sciences Division, School of Medicine, King’s College London, UK
Between 1,000 and 1,150 bacterial species have potential to colonise the human gastro-intestinal (GI) tract, with each individual harbouring around 160 different species (1). The composition of the gut microbiota has received attention as an etiological factor in the development of obesity. It is sensitive to dietary changes and able to alter composition within hours in both animals and humans (2-5). Independently of diet, the gut microbiota is able to influence host inflammatory responses.
The bacterial components of Gram-negative bacteria, such as lipopolysaccharide (LPS), trigger innate immune responses in the host which can lead to weight gain (6). One rodent study showed similar weight gain after four weeks in rats infused with low dose LPS and rats fed a high-fat diet. When CD14 -/- rats were infused with LPS, no weight gain occurred (7). In much the same way, Toll-like receptor (TLR) 4-deficient mice, which are unable to respond to LPS, are protected from high-fat diet-induced obesity and insulin resistance (8).
Many bacteria produce butyrate, including the Eubacterium rectale–Clostridium coccoides group and Faecalibacterium prausnitzii (9). Butyrate inhibits lymphocyte proliferation, interleukin (IL)-2 and interferon (IFN)-γ (10) – it is this anti-inflammatory action that explains butyrate’s therapeutic effects in inflammatory bowel disease (IBD) patients.
Some GI bacteria can suppress host Fasting-Induced Adiposity Factor (Fiaf) and tight junction proteins such as ZO-1 and occludin expressed in the intestinal epithelia. Fiaf plays a central role in triglyceride metabolism (10,11). This glycoprotein inhibits lipoprotein lipase production in adipose tissue and modulates fatty acid oxidation in both adipocytes and skeletal muscle (12). Suppression of tight junction proteins increases intestinal permeability (13).
Evidence suggests that the GI microbiota in the obese is different from the normal weight subject. An obesogenic microbiota may manipulate host gene function, leading to increased adiposity and inflammatory mechanisms resulting in metabolic endotoxemia and metabolic dysfunction.
1. Qin J, Li R, Raes J, Arumugam M, Burgdorf K, Manichanh C, et al. A human
gut microbial gene catalogue established by metagenomic sequencing.
2. Arumugam M, Raes J, Pelletier E, Le Paslier D, Yamada T, Mende D, et al.
Enterotypes of the human gut microbiome. Nature 2011 12 May; 473:174-
3. Ley R, Turnbaugh P, Klein S, Gordon J. Microbial ecology: Human gut
microbes associated with obesity. Nature 2006;444:1022-1023.
4. Schwiertz A, Taras D, Schäfer K, Beijer S, Bos N, Donus C, et al. Microbiota
and SCFA in Lean and Overweight Healthy Subjects. Obesity
2009;18(1):190-195. 5. Wu G, Chen J, Hoffman C, Bittinger K, Chen Y, Keilbaugh S, et al. Linking
long-term dietary patterns with gut microbial enterotypes. Science
6. Harris K, Kassis A, Geneviève M, Chieh C. Is the Gut Microbiota a New
Factor Contributing to Obesity and Its Metabolic Disorders? Journal of
7. Cani P, Amar J, M. A. Iglesias M, Poggi M, Knauf C, Bastelica D, et al.
Metabolic endotoxemia initiates obesity and insulin resistance. Diabetes
8. Shi H, Kokoeva M, Inouye K, Tzameli I, Yin H, Flier J. TLR4 links innate
immunity and fatty acid–induced insulin resistance. The Journal of Clinical
Investigation 2006 11 November;116(11):3015-3025.
9. Balamurugan R, George G, Kabeerdoss J, Hepsiba J, Chandragunasekaran
A, Ramakrishna B. Quantitative differences in intestinal Faecalibacterium
prausnitzii in obese Indian children. Br J Nutr ;103(03):335-338.
10. Macia L, Thorburn A, Binge L, Marino E, Rogers K, Maslowski K, et al.
Microbial influences on epithelial integrity and immune function as a basis for
inflammatory diseases. Immunol Rev 2012;245(1):164-176.
11. Kim H, Youn B, Shin M, Namkoong C, Park KH, Baik JH, et al. Hypothalamic
Angptl4/Fiaf Is a Novel Regulator of Food Intake and Body Weight. Diabetes
2010 November 01;59(11):2772-2780.
12. Esteve E, Ricart W, Fernández-Real J. Gut microbiota interactions with
obesity, insulin resistance and type 2 diabetes: did gut microbiote co-evolve
with insulin resistance? Current Opinion in Clinical Nutrition and Metabolic
Care September 2011;14(5):483-490.
13. Cani P, Rodrigo B, Knauf C, Aurélie W, Neyrinck A, Delzenne N, et al.
Changes in Gut Microbiota Control Metabolic Endotoxemia-Induced
Inflammation in High-Fat Diet–Induced Obesity and Diabetes in Mice.
Diabetes June 2008 June 2008;57(6):1470-1481.