The human microbiome

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.

Microbiome refers to all the microbial life that exists in a specific niche. In the case of humans that means a lot of bacteria, viruses, fungi, parasites, and a very old class of single-celled organisms called archaea. The organisms include commensals and pathogenic microorganisms. Many articles distinguish "microbiome" and "microbiota" to differentiate the collective genomes of the microorganisms or the microorganisms themselves, respectively. However, these terms are largely synonymous.

A number of advances have allowed scientists to make major advances in understanding the microbiome. Specifically, we now have the molecular tools to perform gene expression analysis for an entire microbial community in the new discipline of metagenomics and analyze the massive results with new methods of mathematical analysis.

The human body contains over 10 times more microorganisms than human cells. The existence of a remarkably diverse and enormously large microbial world on us and in us first began to come to light in the late 1990s. We are learning more and more about the individual locations of the human host that have different populations of microbes and about differences among humans that contribute to or account for susceptibility to infectious diseases as well as autoimmune diseases and even obesity and cancer.

The nasopharyngeal microbiome has become an area of research by our group led by Qingfu Xu, Ph.D., at the Rochester (N.Y.) General Hospital Research Institute in collaboration with Melinda M. Pettigrew, Ph.D., at the Yale School of Public Health, New Haven, Conn., and Dr. Janet R. Casey at Legacy Pediatrics, also in Rochester. The traditional view of the immune system is undergoing reassessment as we learn that our microbiota has coevolved with our immune system, and each exerts influence over the other. Our group has a special interest in the impact of the nasopharyngeal microbiome on the innate immune response in that physiologic niche, and the way the innate immune system modifies the microbiome. With a special interest in the bacteria that cause respiratory infections such as acute otitis media, acute sinusitis, bronchopneumonia, and pneumonia, we have identified how microbes like Streptococcus pneumoniae, Haemophilus influenzae, and Moraxella catarrhalis compete and synergize in the nasopharynx to cause infections.

Also, we seek to better understand how respiratory viruses like respiratory syncytial virus (RSV), influenzae, parainfluenzae, rhinovirus, and others facilitate the overgrowth of S. pneumoniae, H. flu, and M. catarrhalis in the nose such that they convert from commensals to pathogens. But the synergy goes both ways, as we have recently found that S. pneumoniae facilitates upper respiratory viral infections.

Up to now most of the work on the human microbiome has focused on the gut, and nearly all studies have occurred in adults. Perhaps readers are aware of the use of "fecal microbiota transplantation" as a treatment/cure for Clostridium difficile infection. Unhealthy gut microbiota in premature neonates are a major contributing factor in necrotizing enterocolitis.

For decades, physicians have been taught that obesity is a problem derived from excessive caloric intake and inadequate caloric consumption through activity, plus vaguely defined differences in "metabolism." As a consequence, we checked for hypothyroidism � I never found a case. New research has shown that there is a difference in the "metabolism" of obese patients, but the difference is how the individual gut microbiota metabolizes our food. It turns out the thinner individuals have a microbiota that is less efficient in breaking down the food we ingest to allow efficient absorption into the bloodstream, whereas obese individuals have a more efficient microbiota that facilitates absorption of a greater percentage of the proteins, carbohydrates, and fats that are ingested. So the pathway to treatment of obesity may lie in the study of the microbiome!

It turns out that the microbiota of the skin is highly diverse. The microbiota colonizing the antecubital fossa is different from that of the forearm or biceps or axillae. When atopic dermatitis flares, it is often in the antecubital fossa, and it is caused by overgrowth of Staphylococcus aureus. The microbiome of a patient with atopic dermatitis is different from that of a person without atopic dermatitis, and the former microbiota is more permissive to S. aureus becoming a pathogen rather than a commensal of the skin.

Prevention of urogenital infections in girls depends on a healthy vaginal microbiota. Bacterial vaginosis requires the establishment of overgrowth by Gardnerella vaginalis and Peptostreptococcus anaerobius that can only occur if the resident microbiota is unable to control the proliferation of these bacteria. Only if the microbiota of the perineum, urethra, and bladder will allow potential urinary tract infection pathogens access to epithelial attachment sites can infection become established.

A last topic for this column is the role of the microbiota in autoimmune diseases. In particular, I find it fascinating to learn that aberrant, unstable intestinal microbiota can lead to a leaky intestinal mucosal barrier. Combined with inadequate innate immune responses in the gut, progression may occur that allows antigens from microbes that cross-react with antigens of self in the pancreas to stimulate autoimmune antibodies. Similar pathogenic mechanisms may contribute to inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and other autoimmune diseases.

I anticipate future research will establish the makeup of a healthy microbiota associated with protection from the diseases mentioned here. With that knowledge, the next efforts in research will focus on how to convert an unhealthy microbiota to a healthy one. If the efforts succeed, I see new promising treatments in the future.

Dr. Pichichero, a specialist in pediatric infectious diseases, is director of the Rochester (N.Y.) General Research Institute. He is also a pediatrician at Legacy Pediatrics in Rochester. The microbiome research at the Rochester General Hospital Research Institute is supported by the National Institutes of Health and the National Institute for Deafness and Communication Disorders. To comment, e-mail him at pdnews@ frontlinemedcom.com.