Obesity—A Disease With Many Aetiologies Disguised in the Same Oversized Phenotype

Has the Overeating Theory Failed?

Peter Stenvinkel


Nephrol Dial Transplant. 2015;30(10):1656-1664. 

In This Article

Gut Microbes—Trillions of Friends and Foes in the Obesity Battle

The nutritional value of what we eat is influenced by the gut microbiota and microbiome (Figure 2). In mice, the switch to a high-sucrose and high-fat 'Western' diet from a low-fat, plant polysaccharide-rich diet led to a rapid shift in the microbiota.[87] As a study in twins discordant for obesity showed that fat mass and obesity-associated metabolic phenotype were transmissible to mice with faecal cultures,[88] it elegantly demonstrates the importance of the gut microflora for the obese phenotype. It has been reported that the 'obese microbiota' is characterized by a larger proportion of Firmicutes and lower Bacteroidetes compared with lean controls.[13] The gut microbiota may play a part in the development of obesity via several mechanisms, such as increased gut permeability, metabolic endotoxemia and the production of short-chain fatty acids, butyrate, proprionate and acetate,[89] which protect against diet-induced obesity.[90] As bacteria producing short-chain fatty acids have effects on the epigenetic regulation of the free fatty-acid receptor,[91] dietary interventions that manipulate the gut microbiome could be a novel epigenetic approach in the treatment of obesity. Indeed, changes in the gut microbes could be reversed by dieting and weight loss.[92] Intake of specific components of food, such as fatty acids, carbohydrates, micronutrients, prebiotics and probiotics, could not only have consequences for the gut microbiota composition, but also modulate the expression of genes in the liver, adipose tissue and muscle, which in turn stimulate or counter obesity.[92] The microbial metabolism is not only important to consider in the management of obesity. A link between gut flora metabolism of dietary phosphatidylcholine and CVD has been reported.[93] Also, the recent finding that the gut microbiota generate pro-atherogenic metabolites from dietary (read meat) l-carnitine[94] reveal an intriguing connection between the trillions of living friends and foes in our gut and human morbidity and nutrition. Indirect support for a link between gut microbiota and obesity comes from the experience that antibiotics and probiotics promote growth in productive animals.[95] Indeed, antibiotic exposure during the first 6 months of life associates with overweight also in children.[96] With better understanding of the ability of both probiotics and antibiotics to harvest energy from the host gut, new dietary treatments for obesity targeting the microbiome may emerge.[95] The recent finding that non-caloric artificial sweeteners (such as saccharin, sucralose and aspartame) induce glucose intolerance by changing the gut microbiota towards a balance known to be associated with a susceptibility to metabolic disease certainly call for caution.[97]