Commentary

The Gift That Keeps on Giving


 

Although unraveling the human genome has been exciting and potentially beneficial, I was a bit dismayed to discover that our genes barely outnumber those of the chimpanzee and, in fact, are only 50% greater in number than those of the fruit fly. If they were able to communicate, even the most discriminating chimpanzee – and especially the humble fruit fly – would likely admit that they are several rungs below us on the animal kingdom ladder. Fortunately, it turns out that this is not the whole story.

The human microbiome project (HMP), close on the heels of the genome undertaking, has found that we have many more genes working for us than those located on the strands of our DNA. The HMP analysis reveals that each of us has more than 100 trillion microorganisms living in the many nooks and crannies of our bodies, with the highest concentration in the gastrointestinal tract. This population of microbes is incredibly diverse, and its exact composition is unique to each of us. Thus, in addition to the individuality granted to us by the genes we receive from our parents, each of us is also a distinctive and rather complex ecosystem.

Not only do these creatures live in and on us peacefully most of the time, they also add to our genetic complement. Whereas our DNA contains only 23,000 genes, these microorganisms in aggregate account for 100 times more genes, several of which transcribe proteins that are essential for our normal daily functioning. For example, they manufacture enzymes that allow digestion of complex carbohydrates that account for more than 10% of our daily calories and that would be indigestible if it were not for the contributions of this microscopic workforce. They also make a variety of vitamins (for example, folic acid, B2, and B12), and they have the capability of gearing production to one’s needs depending on diet and other circumstances. Furthermore, the microbiome likely plays a significant role in the development of our immune system.

When this large population of indigenous bacteria is in appropriate balance, all is well. However, when the equilibrium among species is disrupted by antibiotic therapy or other environmental influences, one or more of a long list of maladies may result. Alterations in the microbiome have been implicated as being a factor in diseases as diverse as colon and pancreatic cancer, diabetes, autism, multiple sclerosis, irritable bowel syndrome, and Clostridium difficile colitis. The latter, usually caused by antibiotic therapy, has even been treated successfully by restoring the microbiome to its normal state by means of a stool transplant from a normal donor. The relationship between the composition of the microbiome and the other disorders is less well understood but is fertile ground for further studies. Such investigations may open doors to future therapies for heretofore untreatable diseases.

Particularly fascinating is the association between the microbiome and the nutritional state. Since microbiomes play an important role in processing what we eat, it makes sense that these microscopic travelers might in part determine our body habitus. Dr. Jeffrey Gordon and his associates at Washington University, St. Louis, have investigated this intriguing prospect (Nature 2006;44:1022-3). They have shown in both animal and human studies that the composition of the microbiome is closely related to the degree of obesity or leanness of the subjects. Of the 100 or so known phyla of bacteria, only two, Bacteroidetes and Firmicutes, account for more than 90% of the microbes in our gastrointestinal tract. Obese mice and humans have a higher ratio of firmicutes to bacteroidetes than do their lean counterparts. Moreover, transplanting the microbiome from obese mice to germ-free animals results in an increase in the body fat of the latter group. Additionally, obese individuals who effectively diet over time increase their intestinal Bacteroidetes-to-Firmicutes ratio.

A common topic of discussion in Surgery News is the worldwide epidemic of obesity and its treatment with a variety of surgical procedures. It is within the realm of possibility that simply altering the microbiome of obese patients might help to resolve this affliction, which impairs the quality of life of so many.

So what is the gift that keeps on giving? It is our microbiome. For more than a century, bacteria have been considered one of the scourges of mankind. It is appropriate as the holiday season approaches that we finally acknowledge the contributions that these usually despised organisms make to our daily welfare. In turn and in the spirit of giving back, we can take some pride in the fact that we provide a warm and hospitable home for these friendly symbionts.

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