Even though we have started to appreciate the importance of human microbiome relatively recently, it is no longer a question’ if the microbiome is important?’ but rather ‘how the microbiome affects us?’. I define human microbiome as the total diversity of microbes in and on human body, however, this definition is definitely simplified version and for those interested in the subtleties of its use can go and read some of the debate in here.
Whatever the definition is, we already have clear evidence that human microbiome affects many aspects of our health including our ability to fight pathogens, regulation of immune system and disease development and even human behaviour. Human digestive system contains one of the greatest diversity of microbes and therefore, it is not surprising that these microbes could respond to our diet and influence the body’s metabolism. Indeed, a recent study by Ridaura et al. suggests that human microbiome and its response to our diet can be linked to obesity in humans.
In the study scientists have transplanted gut microbiome of human twins, one of which was lean and the other obese, into germ-free mice and attempted to answer three main questions:
1. Does the microbiome of lean and obese individuals differ?
2. How the gut microbiome affects the host metabolism?
3. Does the diet have an impact on microbiome?
Initially researchers have collected fecal samples from twin pairs (lean and obese individuals in each pair) and fed them to mice that had no gut microbiome. The question is can microbiome transplantation replicate human phenotype in mice? And the answer is yes. The mice that received the transplant from the obese twin have gained significantly more weight and fat tissue compared to the mice that received lean individual’s microbes.
Next, using RNA sequencing scientists estimated the differences in the amounts of different enzymes made between mice receiving transplants from different donors. They found that mice with obese twin microbiome had increased production of proteins involved in stress responses, detoxification, and production of certain amino acids. In particular, increase in branched chain amino acid production showed similar pattern to what has been previously found in people with insulin-resistance (which can lead to diabetes). With regards to the mice that harboured lean individual’s microbes, they had increased production of enzymes required for plant polysaccharide digestion and short chain fatty acid production. These results suggest that microbiota from lean individual allows mice to more effectively digest the food which consequently prevents deposition of fat tissues (importantly mice in both groups ate the same amount of food throughout the experiment).
Mice, like some other animals, are coprophagic, that is they eat feces. Consequently, there is a potential for transfer of the mice microbiome from one mouse to another. Therefore, researchers had transplanted microbiota from lean and obese twin to different mice, waited until the microbiota had established in the gut and cohoused them in the same cage. Amazingly, the obese mice that were cohoused with lean mice had significantly lower increase in fat mass compared to the mice that were cohoused with obese animals. The lean mice remained lean. The analysis of bacterial taxa in the lean and obese mice showed that there was a transfer of certain bacterial taxa from the lean to obese mice but not vice verse. In addition when scientists put germ-free mice in a same cage with lean and obese animals the germ-free mice acquired lean mice phenotype, suggesting, that leanness associated bacteria have greater fitness and therefore, are better able to invade and establish in the gut of another animal.
Analysis of specific bacterial species in the lean mice indicated increase in certain taxa (e.g. Bacteroidetes and Ruminococcaceae) some of which are linked to processes such as increased branched chain amino acid and polysaccharide degradation. When some of these taxa were separately cultured and then fed to germ-free mice it was found that although, the mice did indeed develop lean phenotype this phenotype was not transmitted to the cohoused obese mouse, suggesting that bacterial invasiveness and phenotype development also depend on overall bacterial community context.
Finally, the researchers wanted to determine if specific diet affects the ability to transfer microbes from one animal to another. Scientists have given mice special food that was either low in saturated fats and high in fruits and vegetables (loS-hiFV) or high in saturated fats and low in fruits and vegetables (hiS-loFV) (both types were based on nutritional definition by U.S. The National Health and Nutrition Examination Survey). When lean and obese mice were housed and fed loS-hiFV diet the microbiota from lean animals successfully invaded and established in obese mice. However, when mice were fed hiS-loFV not only did both groups gained weight (lean less than obese) but also microbiota from lean mice did not transfer to obese mice suggesting that the diet of high saturated fats and little fruits and vegetables prevents leanness-associated bacteria establishment in obese mice.
Considering the fact that there are at least ten times more bacterial cells in and on our body it is not surprising that they can significantly affect our health. Studies like this one help us to better understand human microbiome function and are already leading to improved medical treatments. It is clear that human body is an ecosystem in itself and we will have to understand how the different parts of this ecosystem interact in order to better predict the subtle changes affecting our health.
Ridaura VK, Faith JJ, Rey FE, Cheng J, Duncan AE, Kau AL, Griffin NW, Lombard V, Henrissat B, Bain JR, Muehlbauer MJ, Ilkayeva O, Semenkovich CF, Funai K, Hayashi DK, Lyle BJ, Martini MC, Ursell LK, Clemente JC, Van Treuren W, Walters WA, Knight R, Newgard CB, Heath AC, & Gordon JI (2013). Gut microbiota from twins discordant for obesity modulate metabolism in mice. Science (New York, N.Y.), 341 (6150) PMID: 24009397