The gut microbiota in obesity and weight management: microbes as friends or foe?

Obesity is caused by a long-term difference between energy intake and expenditure — an imbalance that is seemingly easily restored by increasing exercise and reducing caloric consumption. However, as simple as this solution appears, for many people, losing excess weight is difficult to achieve and even more difficult to maintain. The reason for this difficulty is that energy intake and expenditure, and by extension body weight, are regulated through complex hormonal, neural and metabolic mechanisms that are under the influence of many environmental factors and internal responses. Adding to this complexity, the microorganisms (microbes) that comprise the gut microbiota exert direct effects on the digestion, absorption and metabolism of food. Furthermore, the gut microbiota exerts a miscellany of protective, structural and metabolic effects both on the intestinal milieu and peripheral tissues, thus affecting body weight by modulating metabolism, appetite, bile acid metabolism, and the hormonal and immune systems. In this Review, we outline historical and recent advances in understanding how the gut microbiota is involved in regulating body weight homeostasis. We also discuss the opportunities, limitations and challenges of using gut microbiota-related approaches as a means to achieve and maintain a healthy body weight. This Review outlines evidence that the gut microbiota is involved in regulating body weight homeostasis. In addition, the opportunities, limitations and challenges of using gut microbiota-related approaches as a means to achieve and maintain a healthy body weight in people with overweight or obesity are discussed. Key points Two decades ago, pioneering studies showed that prebiotic-induced changes in the gut microbiota affect adipose mass in rats. Numerous dietary factors, such as fat, proteins and fibre, shape the gut microbiota and eventually contribute to the regulation of host energy metabolism through specific microbial metabolites. So far, no proof has been provided that one specific bacteria or group of bacteria can predict the onset of obesity or body weight loss in humans. The regulation of host energy metabolism is under the influence of many metabolites produced and/or modified by the gut microbiota, and some of these molecules might become drug candidates. Demonstrating whether particular microbiota compositions are beneficial or detrimental for body weight management remains a challenge and requires future studies to design person