HOW DOES THE MICROBIOME AFFECT HEALTH?
The microbiome has been implicated in a variety of diseases. In fact, it has been suggested to have a role in nearly every disease in which it has been studied, including a wide array of metabolic diseases, inflammatory bowel disease, immune-related conditions, cardiovascular and neurological diseases, and cancer. Even depression, anxiety, and autism have been linked to differences in the microbiome. Although the evidence for a direct role of the microbiome has been shown in some diseases, in most cases only an association between bacteria and the disease has been made: it is not clear what is cause and what is effect.
As might be expected given the role of the microbiome in affecting our metabolism, there are clear links between the microbiome and metabolic diseases such as obesity and type 2 diabetes. The gut microbiome of obese people is very different from that of nonobese people. Thinner people have a gut microbiome that often contains a group of bacteria called Bacteroides. In contrast, obese people often have more of another type called Firmicutes. Interestingly, transfer of the gut microbiome from mice that are genetically disposed to become obese into germ-free mice that do not have a genetic predisposition to obesity resulted in increased weight gain and fat accumulation in the germ-free mice. The same results can be reproduced using a human microbiome: Introduction of the microbiome from a thin human into a sterile mouse can prevent obesity, but the microbiome of an obese human cannot. Thus, the microbiome is not only associated with obesity, but it may directly help control weight gain. As with obese individuals, diabetics have a very different microbiome from that of nondiabetics.
A clear role for the microbiome in health has been demonstrated in people with Clostridium difficile (“C. difficile”) infections. These intestinal infections occur in a variety of circumstances including when patients are hospitalized for other illnesses. Transfer of fecal material from a healthy person to one who has C. difficile (i.e., a “fecal transplant”) has been shown to be incredibly effective in treating this disease. Similarly, people with inflammatory bowel diseases (IBD) such as ulcerative colitis (UC) and Crohn’s disease (CD) have problems with their digestive tract. People with CD and UC have a different bacterial microbiome from each other and from that of healthy people. In some cases fecal transplants have caused a dramatic reduction in symptoms. These various observations suggest that the associations between the microbiome and disease may not only be causal associations, but that the microbiome can directly influence health. Moreover, it suggests a novel therapeutic strategy to treat IBD and C. difficile patients.
Links also have been made between the gut microbiome and heart disease. Diets high in meat have been linked to heart disease and are comprised of and contain copious amounts of carnitine. Our microbiome converts carnitine into a compound called TMAO, whose levels have been associated with heart failure. Alterations in diet can alter the amount of TMAO, and thus dietary modifications may reduce the severity of heart failure in patients with poorly functioning hearts. These observations indicate that the microbiome can be directly associated with a major human disease and also can suggest a novel therapeutic strategy for reducing heart failure. Given that the bacteria and gene that make TMAO are known, substitution of our indigenous bacteria that make TMAO for one(s) that have been engineered not to produce this compound should improve human health. Although this technology may still be years away, it offers a much safer prospect to controlling certain diseases using bacterial prophylactics.