Clinica Medica “A. Murri”, Department of Biomedical Sciences and Human Oncology, University of Bari, Italy

Abbreviations

BMI: Body Mass Index, FIAF: Fasting-Induced Adipocyte Factor, LPS: Lipopolysaccharides

Obesity is a chronic disease defined as body mass index (BMI) of ≥30 kg/m². Both obesity and overweight (BMI of 25 to 29.9 kg/m²) represent a major public health issue worldwide in children, adolescents and adults leading to increased morbidity and mortality. In general, obesity is a complex disease that results from the interplay between several determinants. From time to time, a role for host genetics, environment, biological factors, pregnancy and lactation history in mothers, social and cultural influence, and imbalance between energy intake and expenditure has been advocated [1-4]. Dietary factors modulate the composition of the gut microbiota [5].

Recently, an increased number of studies have evaluated the role of intestinal microbiota in the development of the epidemic obesity. Intestinal microbiota play a pivotal role in regulating endogenous energy and metabolic pathways [6]. Alterations in gut microbiota have been observed in obese animals and humans according to phylum-level, bacterial diversity and representation of bacterial genes and metabolic pathways [7,8]. In this respect, an increase in Firmicutes associated with reduction in Bacteroidetes is observed in obesity [9,10]. The analysis of the faecal microbiota of obese and lean twins have shown that both subjects displayed the core gut microbiome, but obese individuals were characterized by reduced microbial diversity and abnormal microbiota metabolic pathways [11].

Intestinal microbiota influences energy harvest and storage [12], since microbiota can regulate nutrient absorption and host genes [13]. Microbiota might modulate energy balance through several pathways: an increased intestinal absorption of monosaccharides and the production of short-chain fatty acids through the fermentation of indigestible polysaccharides, an increased hepatic lipogenesis via carbohydrate and sterol response-element binding proteins, a suppression of Fasting-Induced Adipocyte Factor (FIAF) that in normal conditions inhibits lipoprotein lipase. Additional mechanisms include suppression of adenosine monophosphate-activated protein kinase, interplay between products of polysaccharide fermentation and G-protein-coupled receptor 4, increased intestinal permeability for bacterial Lipopolysaccharides (LPS) in response to the consumption of high-fat diets leading to an elevated systemic LPS level and low-grade inflammation [14].

To date, the accumulating evidences suggest that the gut microbiota contribute to adiposity by modulating the metabolic network involved in bioenergetics. Thus, manipulation of intestinal microbiota represents a novel and fascinating approach to shift a dysmetabolic status into a healthy condition. Moreover, by modifying host energy balance and treating obesity is a chance to prevent other metabolic diseases.

References

1. Bouchard C, Tremblay A, Despres JP, Nadeau A, Lupien PJ, et al. (1990) The response to long-term overfeeding in identical twins. N Engl J Med 322: 1477-1482.
   


2. Scuteri A, Sanna S, Chen WM, Uda M, Albai G, et al. (2007) Genome-wide association scan shows genetic variants in the FTO gene are associated with obesity-related traits. PLoS Genet 3: e115.
   


3. Abbasi A, Corpeleijn E, Postmus D, Gansevoort RT, de Jong PE, et al. (2010) Plasma procalcitonin is associated with obesity, insulin resistance, and the metabolic syndrome. J Clin Endocrinol Metab 95: E26-31.
   


4. Mozaffarian D, Hao T, Rimm EB, Willett WC, Hu FB (2011) Changes in diet and lifestyle and long-term weight gain in women and men. N Engl J Med 364: 2392-2404.
   


5. Jess T (2014) Microbiota, antibiotics, and obesity. N Engl J Med 371: 2526-2528.
   


6. Delzenne NM, Cani PD (2011) Interaction between obesity and the gut microbiota: relevance in nutrition. Annu Rev Nutr 31: 15-31.
   


7. Ley RE, Turnbaugh PJ, Klein S, Gordon JI (2006) Microbial ecology: human gut microbes associated with obesity. Nature 444: 1022-1023.
   


8. Hildebrandt MA, Hoffmann C, Sherrill-Mix SA, Keilbaugh SA, Hamady M, et al. (2009) High-fat diet determines the composition of the murine gut microbiome independently of obesity. Gastroenterology 137: 1716-1724.
   


9. Ley RE, Backhed F, Turnbaugh P, Lozupone CA, Knight RD, et al. (2005) Obesity alters gut microbial ecology. Proc Natl Acad Sci U S A 102: 11070-11075.
   


10. Turnbaugh PJ, Hamady M, Yatsunenko T, Cantarel BL, Duncan A, et al. (2009) A core gut microbiome in obese and lean twins. Nature 457: 480-484.
    


11. Tilg H (2010) Obesity, metabolic syndrome, and microbiota: multiple interactions. J Clin Gastroenterol 44 Suppl 1: S16-18.
    


12. Backhed F, Ding H, Wang T, Hooper LV, Koh GY, et al. (2004) The gut microbiota as an environmental factor that regulates fat storage. Proc Natl Acad Sci U S A 101: 15718-15723.
    


13. Jumpertz R, Le DS, Turnbaugh PJ, Trinidad C, Bogardus C, et al. (2011) Energy-balance studies reveal associations between gut microbes, caloric load, and nutrient absorption in humans. Am J Clin Nutr 94: 58-65.
    


14. Backhed F, Manchester JK, Semenkovich CF, Gordon JI (2007) Mechanisms underlying the resistance to diet-induced obesity in germ-free mice. Proc Natl Acad Sci U S A 104: 979-984.