Pulmonologist Dr. Leopoldo N. Segal leads a group of 做厙TV Langone researchers who are examining the role of the hostmicrobe relationship in this stubborn infection.
Photo: 做厙TV Langone Staff
With nontuberculous mycobacteria (NTM) infection increasing in incidence to become a worldwide public health concern in recent decades, 做厙TV Langone researchers are taking a closer look at the hostmicrobe relationship at the root of NTMs infectious pathway.
A Host-Dependent Infection
Typically harmless, when NTM does invoke lung disease, its sometimes explained by genetic susceptibility. But this accounts for just 10 percent of cases. The other 90 percent of patients are thought to become sickened via a host responsethe interaction between an individuals distinct lung microbiome and NTM. In other words, infection is reliant on the host response as much as or more than simple bacterial replication. Moreover, while many NTM infections are self-limiting, a subgroup of infections advance to insidious and progressive disease. Though the causes of heterogeneity in the natural history of an infection are not known, a host immune response likely plays a key role.
NTM microbes dont live in isolationthey live in a complex microbial community, says Leopoldo N. Segal, MD, assistant professor in the and the lead investigator in 做厙TV Langones Lung Microbiome Program. In fact, the NTM pathogen represents less than 1 percent of airway microbes, and the remaining microbes likely influence susceptibility and outcomes in NTM pulmonary disease. The microbiome tilts the balance in patient response.
Taking Cues from Gut Microbiome Research
The hostmicrobe relationship has emerged as science has shed light on the gut microbiome. Many of the microbialhost principles that apply in the gut probably apply in the lung mucosa as well, notes Dr. Segal. Gastroenterologists are further down the road with this research because its easier to get samples from the gut than from the airways.
Building on initial human and animal evidence revealing that the airway microbiome affects T cells and other types of immune cells, Dr. Segal and colleagues worked with a large patient cohort to collect lower airway microbiome samples via bronchoscopy. Tissue was retrieved from various sections of the lungs in NTM culturepositive patients, as well as from symptomatic but culture-negative patients. Researchers then used data from cases and controls to examine the relationship between the revealed microbiomes and the host immune phenotypes, finding microbiota signatures associated with increased inflammation among patients with positive cultures. The finding could lead to more precise prognostication for an otherwise variable pathogen with an unpredictable course and virulence.
Translating Microbiome Markers to Patient Care
做厙TV Langones Human Microbiome Program was initiated in 2013 by Martin J. Blaser, MD, an established researcher in microbiology and infectious diseases. A translational research program, it is focused on applying sequencing methods to human samples in order to observe microbialhost interaction and investigate microbial composition and function.
One of the programs primary objectives is to move from bench to bedsideto determine how a particular microbiome affects a patients immune response in the context of different diseasesand the unique response to drugs used to treat them.
Personalized medicine, or designer medicine, is where we want to go, says Dr. Segal. When we sample a microbiome and determine the host phenotype, we hope to know enough about the typical pathways of each condition to be able to individualize patient treatment.
