Obesity
The connections of the gut microbiota to obesity are interwoven with connections to diabetes, so you might be interested in that advanced topic page also. (They aren't inextricably linked though...there are many obese individuals who aren't diabetic, and some diabetic individuals who aren't overweight or obese. Studying these individuals can be particularly revealing.)
For many decades until not that long ago, the conventional scientific wisdom was that a calorie from any food source was equivalent, that these calories were the same for everyone, and that obesity was a simple arithmetic problem of calories consumed minus calories burned being greater than zero for an extended period of time. None of these ideas are true.
That's largely (but not entirely) due to the gut microbiota, which responds differently to various dietary compounds, which differs between individuals and within an individual over time, and which exerts a number of direct and indirect effects on the host via the endocrine and immune systems that complicate the simple arithmetic of calories. It remains true, of course, that obesity is the result of a long term imbalance of energy flows. However, an individual's energy intake depends in part on how effectively his or her gut microbiota extracts energy from undigested dietary compounds, and an individual's energy expenditure is strongly influenced by metabolic regulation which is dependent upon the gut microbiota as well as host physiology. It may prove that the indirect effects of diet on energy flows, acting in part through the composition and activity of the gut microbiota, are at least as important for obesity as the direct effects of diet energy content, as measured by the total energy released from food in a calorimeter.
This topic of research was catapulted into prominence by some early papers (meaning almost a decade old, this field moves fast) from the lab of Jeff Gordon at Washington University. They found that the gut microbiota differed in lean and obese mice and humans, and that being lean or obese could be transferred to otherwise identical, previously germ-free mice by implanting them with the corresponding microbiota. They also demonstrated that the gut microbiota is intimately involved with metabolic regulation, previously thought to be under the complete control of host hormones. These findings have proved robust, but another claim made in these early papers, that obesity is marked by a higher ratio of bacteria in the Firmicutes phylum relative to those in the Bacteroidetes phylum, has not been found consistently in other studies. (These are the two most abundant phyla of bacteria in the guts of most mammals.) The Gordon lab probably didn't get the data wrong in the early reports, but it turns out that the pattern doesn't always hold across different groups of people and in different contexts.
One extremely important recent realization is that chronic low-grade inflammation is a hallmark of both obesity and diabetes, and may in fact be the bridge (or one of the bridges) between these two closely linked conditions. One mechanism is that certain gut microbes from the Proteobacteria phylum that are increased by a high-fat, high-sugar diet seem to be more prone than other gut microbes to cause local inflammation, and those same microbes are better able to tolerate inflammation so they perpetuate themselves in a vicious cycle. The integrity of the gut barrier can be reduced in this situation, allowing more live bacteria and bacterial compounds to escape the gut, also causing inflammation that persists in a vicious cycle.
Another striking observation involves what happens after gastric bypass surgery, which is a dramatic procedure that changes the plumbing of the digestive tract to reduce nutrient intake from the diet. While somewhat risky, it's one of the most successful interventions we have for reversing severe obesity, and it also dramatically decreases the severity of type 2 diabetes that often accompanies extreme obesity. The striking observation is that the gut microbiota changes very rapidly after gastric bypass surgery, and diabetes symptoms also decrease in severity quite rapidly, even though the weight loss after surgery is much more gradual. This suggests that type 2 diabetes is not (or not entirely) a consequence of obesity itself, it may be caused or perpetuated (at least in part) through the gut microbiota. Perhaps if the microbiota could be altered in other ways, the surgery itself might not be necessary. There is one striking case that I know of that lends some credence to this idea, although it seems the gut microbiota of the patient in question was extremely unusual even compared to that of other obese individuals (see Fei & Zhao below for the original journal article).
For many decades until not that long ago, the conventional scientific wisdom was that a calorie from any food source was equivalent, that these calories were the same for everyone, and that obesity was a simple arithmetic problem of calories consumed minus calories burned being greater than zero for an extended period of time. None of these ideas are true.
That's largely (but not entirely) due to the gut microbiota, which responds differently to various dietary compounds, which differs between individuals and within an individual over time, and which exerts a number of direct and indirect effects on the host via the endocrine and immune systems that complicate the simple arithmetic of calories. It remains true, of course, that obesity is the result of a long term imbalance of energy flows. However, an individual's energy intake depends in part on how effectively his or her gut microbiota extracts energy from undigested dietary compounds, and an individual's energy expenditure is strongly influenced by metabolic regulation which is dependent upon the gut microbiota as well as host physiology. It may prove that the indirect effects of diet on energy flows, acting in part through the composition and activity of the gut microbiota, are at least as important for obesity as the direct effects of diet energy content, as measured by the total energy released from food in a calorimeter.
This topic of research was catapulted into prominence by some early papers (meaning almost a decade old, this field moves fast) from the lab of Jeff Gordon at Washington University. They found that the gut microbiota differed in lean and obese mice and humans, and that being lean or obese could be transferred to otherwise identical, previously germ-free mice by implanting them with the corresponding microbiota. They also demonstrated that the gut microbiota is intimately involved with metabolic regulation, previously thought to be under the complete control of host hormones. These findings have proved robust, but another claim made in these early papers, that obesity is marked by a higher ratio of bacteria in the Firmicutes phylum relative to those in the Bacteroidetes phylum, has not been found consistently in other studies. (These are the two most abundant phyla of bacteria in the guts of most mammals.) The Gordon lab probably didn't get the data wrong in the early reports, but it turns out that the pattern doesn't always hold across different groups of people and in different contexts.
One extremely important recent realization is that chronic low-grade inflammation is a hallmark of both obesity and diabetes, and may in fact be the bridge (or one of the bridges) between these two closely linked conditions. One mechanism is that certain gut microbes from the Proteobacteria phylum that are increased by a high-fat, high-sugar diet seem to be more prone than other gut microbes to cause local inflammation, and those same microbes are better able to tolerate inflammation so they perpetuate themselves in a vicious cycle. The integrity of the gut barrier can be reduced in this situation, allowing more live bacteria and bacterial compounds to escape the gut, also causing inflammation that persists in a vicious cycle.
Another striking observation involves what happens after gastric bypass surgery, which is a dramatic procedure that changes the plumbing of the digestive tract to reduce nutrient intake from the diet. While somewhat risky, it's one of the most successful interventions we have for reversing severe obesity, and it also dramatically decreases the severity of type 2 diabetes that often accompanies extreme obesity. The striking observation is that the gut microbiota changes very rapidly after gastric bypass surgery, and diabetes symptoms also decrease in severity quite rapidly, even though the weight loss after surgery is much more gradual. This suggests that type 2 diabetes is not (or not entirely) a consequence of obesity itself, it may be caused or perpetuated (at least in part) through the gut microbiota. Perhaps if the microbiota could be altered in other ways, the surgery itself might not be necessary. There is one striking case that I know of that lends some credence to this idea, although it seems the gut microbiota of the patient in question was extremely unusual even compared to that of other obese individuals (see Fei & Zhao below for the original journal article).
Selected Scientific Literature
This group of papers from the Gordon lab includes the seminal early papers that pretty much jump-started the current research in this area, and one important recent paper:
Ley et al., 2005: Survey of the composition of the gut microbiota in mice that have genetic mutations that make them obese, compared to their littermates and their mothers that are not obese. (full text)
Ley et al., 2006: Original claim (based on data from humans) that obesity is related to a high ratio of Firmicutes to Bacteroidetes bacteria in the gut. (abstract only)
Turnbaugh et al., 2006: Companion paper to the one above, showing that the gut microbiota of obese mice can harvest more energy from the diet than that of lean mice, and that the trait of higher or lower body mass can be transferred by transplanting the associated gut microbiota. (abstract only)
Bäckhed et al., 2007: Study using mice to show that the gut microbiota can act through the enzyme AMPK and the hormone Fiaf to influence obesity. (full text)
Ridaura et al., 2013: Demonstration that the microbiota of human twins, one of whom is obese and the other not, result in higher and lower body mass respectively, when transplanted into previously germ-free mice that are all fed the same low fat diet. Another important detail is that the additional transmission of a small number of strains in the Bacteroidetes phylum from the lean-microbiota mice to the obese-microbiota mice could prevent the weight gain that would otherwise occur. (full text)
Ley et al., 2005: Survey of the composition of the gut microbiota in mice that have genetic mutations that make them obese, compared to their littermates and their mothers that are not obese. (full text)
Ley et al., 2006: Original claim (based on data from humans) that obesity is related to a high ratio of Firmicutes to Bacteroidetes bacteria in the gut. (abstract only)
Turnbaugh et al., 2006: Companion paper to the one above, showing that the gut microbiota of obese mice can harvest more energy from the diet than that of lean mice, and that the trait of higher or lower body mass can be transferred by transplanting the associated gut microbiota. (abstract only)
Bäckhed et al., 2007: Study using mice to show that the gut microbiota can act through the enzyme AMPK and the hormone Fiaf to influence obesity. (full text)
Ridaura et al., 2013: Demonstration that the microbiota of human twins, one of whom is obese and the other not, result in higher and lower body mass respectively, when transplanted into previously germ-free mice that are all fed the same low fat diet. Another important detail is that the additional transmission of a small number of strains in the Bacteroidetes phylum from the lean-microbiota mice to the obese-microbiota mice could prevent the weight gain that would otherwise occur. (full text)
Cox and Blaser, 2013: Review of the potential mechanisms of microbe-induced obesity.
Clarke et al., 2012: Good overall review of the evidence and mechanisms that link the gut microbiota to obesity. (full text)
Everard and Cani, 2013: Review on diabetes, obesity and the gut microbiota, focused mostly on the issue of gut barrier function and inflammation. (full text)
Cani et al, 2012: Another review by the Cani lab on the gut microbiota and the inflammation link to diabetes and obesity. (full text)
Castagneto and Mingrone, 2012: Review finding rapid improvement in diabetic symptoms after bariatric surgery. (abstract only)
Aron-Wisnewsky et al., 2012: Review on the gut microbiota after bariatric surgery. (abstract only)
Fei and Zhao, 2013: The striking case of an extremely obese, diabetic individual with an extremely proinflammatory gut microbiota, whose health and weight improved dramatically after health interventions that normalized the gut microbiota. (full text)
Clarke et al., 2012: Good overall review of the evidence and mechanisms that link the gut microbiota to obesity. (full text)
Everard and Cani, 2013: Review on diabetes, obesity and the gut microbiota, focused mostly on the issue of gut barrier function and inflammation. (full text)
Cani et al, 2012: Another review by the Cani lab on the gut microbiota and the inflammation link to diabetes and obesity. (full text)
Castagneto and Mingrone, 2012: Review finding rapid improvement in diabetic symptoms after bariatric surgery. (abstract only)
Aron-Wisnewsky et al., 2012: Review on the gut microbiota after bariatric surgery. (abstract only)
Fei and Zhao, 2013: The striking case of an extremely obese, diabetic individual with an extremely proinflammatory gut microbiota, whose health and weight improved dramatically after health interventions that normalized the gut microbiota. (full text)