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Microbiology

Wealth management in the gut

Nature volume 500, pages 538539 (29 August 2013) | Download Citation

People whose guts contain a low diversity of bacteria are found to have higher levels of body fat and inflammation than those with high gut-microbial richness. But dietary intervention can help. See Article p.541 & Letter p.585

To some extent, each of us is a 'super-organism', composed of our own genome and the collective genetic contribution of the non-pathogenic microorganisms that reside in our guts and other organs. A key feature of this aggregate genome is the dynamic nature of its composition, particularly in response to environmental stressors such as high-fat or low-energy diets. Our bodies can maintain health in response to acute dietary changes, but chronic nutrient stress can lead to the increased risk of disease, as is seen in the contribution of high-fat diets and sedentary lifestyles to obesity, diabetes, inflammation and heart disease. However, most overweight people have a normal metabolism, and what distinguishes healthy obese individuals from those with metabolic disease is poorly understood. In this issue, Le Chatelier et al.1 (page 541) and Cotillard et al.2 (page 585) further our understanding of the role of gut microorganisms in this distinction by identifying a correlation between the genetic 'richness' of the gut microbiome — the collective genome of the resident microorganisms — and health.

A prelude to the current work came from surprising evidence3,4 that, in addition to diet and exercise, certain gut bacteria are strongly correlated with, and potentially contribute to, disorders associated with excessive weight. Although all humans host trillions of intestinal bacteria, it was suggested5 that the gut microbiome of each person can be assigned to one of three main groups, called enterotypes, which are dominated by species of the genera Bacteroides, Prevotella or Ruminococcus, respectively. Surprisingly, the distribution of enterotypes seems to be independent of sex, age, body-mass index and nationality. The two latest studies built on these ideas to explore microbial gene complexity as a potential marker of metabolic health.

Le Chatelier et al. describe differences in the number of gut microbial genes (the bacterial richness) between the microbiomes of non-obese and obese Danish individuals. The authors found that high and low bacterial richness could be distinguished on the basis of the abundance of just a small number of bacterial species. They also found that individuals with low bacterial richness had higher overall levels of body fat (adiposity) and accompanying inflammation-associated characteristics than those with high bacterial richness (Fig. 1). Moreover, among the obese volunteers, those with relatively low microbial richness tended to gain more body weight than those with high microbial richness, suggesting that they harbour inflammation-associated gut microbiota.

Figure 1: Benefits of genetic richness.
Figure 1

By comparing the complement of microbial genes in the guts of obese and non-obese individuals, Le Chatelier et al.1 show that people with relatively less-complex microbiomes have higher overall body adiposity and more inflammation-associated characteristics, indicating that they are at higher risk of metabolic diseases than people with a greater gut-bacterial richness. Cotillard et al.2 demonstrate that microbial richness increases, and inflammation decreases, in obese and overweight people with low microbial richness who commence an energy-restricted diet, but that such dietary interventions have little effect in individuals with already high microbial richness.

These findings suggest that stratification of microbial gene richness is predictive of the metabolic and inflammatory status of the host, and may therefore function as a new biomarker. For example, the data revealed that individuals with a microbiome enriched in Bacteroides and some Ruminococcus species had an increased incidence of insulin resistance, fatty liver and low-grade inflammation compared with individuals with a microbiota enriched in Methanobrevibacter species.

A previous study had found6 that a higher dietary intake of animal protein and saturated fat was positively associated with the presence of Bacteroides species in the human gut, whereas plant-based nutrition was associated with Prevotella species. Cotillard et al. show that this is not just an association, but that dietary patterns can predict gut-microbial gene composition. Like Le Chatelier and colleagues, they report that people with low microbial richness (40% of individuals in their study population of obese and overweight French volunteers) had an increased risk of developing metabolic defects compared with those with high microbial richness. The authors then evaluated the effects on these individuals' clinical presentation and microbial composition of 6 weeks of an energy-restricted diet followed by 6 weeks of weight maintenance.

Interestingly, they found that this dietary intervention improved microbial richness and clinical results in individuals who had been classified as having low microbial richness, but that the intervention was significantly less beneficial to those with already high microbial richness (Fig. 1). This suggested that bacterial gene richness is predictive of a person's ability to respond to dietary intervention. Such a concept is promising for clinical research and pharmaceutical drug development, because it opens potential avenues for customizing drugs and reprogramming microbial ecology in individual patients.

Despite these and other advances in our understanding of how bacterial type and diversity influence aspects of health, there remains a debate around the use of three enterotypes as a way of classifying human gut bacteria, and around their physiological significance — some researchers feel that the distinction between microbiomes is less clear cut than simply three dominant types6,7,8,9. This controversy matters, because such classifications may eventually affect how a person's relative risk of disease is gauged and what proactive therapeutic options are considered. However, although these groupings need further clarification, it is clear that there are clinically relevant correlations between microbial diversity and physiology. Indeed, the two studies indicate that microbial composition and bacterial gene richness are sufficient to distinguish healthy obese people from obese people with metabolic disease, as well as those who will respond to energy-restriction therapy. This in turn suggests that categorization of gut microbiota into distinct groups would be an attractive way to use the aggregate microbial genome as a biomarker for predicting the rate of progression in some human disorders, such as inflammatory bowel disease.

These findings also raise the question of whether high microbial gene complexity is merely a reflection of metabolic health or actually offers protection against disease progression. If the former, then microbial conversion from high to low genetic richness would be diagnostic only of a physiological state, as opposed to an indication of risk or a trigger for pathology. Further analysis of the aggregate microbial genomes in multiple populations and testing of microbial transplantation may help to resolve these issues. But in the meantime, be nice to your microbial friends. Although small, they may be powerful allies.

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  1. Sungsoon Fang and Ronald M. Evans are in the Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California 92037, USA.

    • Sungsoon Fang
    •  & Ronald M. Evans
  2. R.M.E. is also at the Howard Hughes Medical Institute.

    • Ronald M. Evans

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Correspondence to Sungsoon Fang or Ronald M. Evans.

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https://doi.org/10.1038/500538a

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