TB lung infection causes changes in the diversity of gut bacteria in mice

May 13, 2014

Johns Hopkins researchers have found evidence in mice that a tuberculosis (TB) infection in the lungs triggers immune system signaling to the gut that temporarily decreases the diversity of bacteria in that part of the digestive tract.

The Johns Hopkins researchers showed that this decrease in diversity of as measured in fecal samples happened quickly—within six days after mice were exposed to an aerosol mixture of M. tuberculosis, the TB bacteria. This prompt shift in diversity, they say, suggests that the is attacking the gut bacteria, decreasing the overall diversity by causing certain bacteria to outgrow others in the gut.

The finding was also replicated using a different strain of the TB microbe, according to a report on the work in the May 12 issue of the online journal PLOS One.

Study leader Kathryn Winglee, a Ph.D. student working at the Johns Hopkins Center for Tuberculosis Research, says the finding is important, because it could lead to improved diagnosis of TB, a disease that infects one-third of the world's population and in 2010 caused 1.4 million deaths.

"The fact that the bacterial populations change in the gut means that we can begin to use this observation for TB diagnosis," Winglee says. "TB diagnosis is currently challenging, but a simple stool sample test that detects changes in the diversity of gut bacteria after TB infection in the lung might improve diagnosis."

The finding also adds to growing evidence that the various parts of the immune system found in throughout the body interact as a "global" organ rather than work as separate, individual sites of immune function. Mucous membranes are the moist linings of areas of the body exposed to the environment, such as the nostrils, mouth, lungs, genitals and intestinal tract. These membranes form a protective barrier against infection and contain immune system cells.

Gut microbes have a complex relationship with the immune system, according to Winglee. For example, individuals with arthritis, type 2 diabetes, asthma and certain other diseases have specific changes in the populations of their compared to healthy people, she explains. "However, there have been very few studies focused on changes in gut bacteria in response to TB infection, especially in individuals whose gut bacterial diversity hasn't already been artificially affected by antibiotics," she says.

To study the effect of TB infection on gut bacteria, the researchers infected mice with M. tuberculosis using an aerosol machine that deposited the bacteria into their lungs. The researchers then studied the various populations of bacteria in the gut until the mice died. They compared samples collected after infection with gut bacteria samples taken before infection to identify the changes in populations. The researchers used genetic and statistical techniques to determine the numbers of species present and their abundance. TB infection caused a decrease in diversity of bacteria in the gut of all mice after infection, followed by a recovery in diversity, until death or one week prior to death.

For example, the relative abundance of a different species of bacteria belonging to two families—higher-level groups that contain various species—called Lachnospiraceae and Ruminococcaceae were higher before TB infection; they were also higher in uninfected mice. Other changes in populations of various species of gut bacteria also contributed to a decrease in diversity, as some bacteria become more prevalent while the population of others dwindled.

"Since TB bacteria were usually not found in the guts of the mice we studied, we believe that the changes in overall bacterial diversity are not caused by their presence there," Winglee says. "Instead, since the span of time when there was a minimum of diversity among bacterial populations that coincided with the most active immune response, we believe that it was the mucosal immune system that caused the shift in diversity."

Very little is known about the effects of specific gut microorganisms in humans, according to Winglee. So finding that there is a significant loss of of gut bacteria with TB infection is a critical step in understanding some of the events that occur during this disease, as well as the role of the mucosal immune system, she says.

"We often think of each part of the mucosal immune system, such as the lungs and gut, to be separated," Winglee notes. "However, the fact that an aerosol causes such rapid changes in the gut suggests that the various parts of the mucosal system throughout the body actually function in some way like a single organ."

Explore further: Relationship between gut bacteria, blood cell development helps immune system fight infection

Related Stories

Relationship between gut bacteria, blood cell development helps immune system fight infection

March 12, 2014
The human relationship with microbial life is complicated. At almost any supermarket, you can pick up both antibacterial soap and probiotic yogurt during the same shopping trip. Although there are types of bacteria that can ...

Breastfeeding promotes the growth of beneficial bacteria in the gut

May 7, 2014
A number of studies have shown that breastfed babies grow slightly slower and are slightly slimmer than children who are fed with infant formula. Children who are breastfed also have a slightly lower incidence of obesity, ...

More than just bacteria: The importance of microbial diversity in gut health and disease

March 10, 2014
The gut microbiota contains a vast number of microorganisms from all three domains of life, including bacteria, archaea and fungi, as well as viruses. These interact in a complex way to contribute towards both health and ...

Research study takes deeper look at the role of gut microbes in the immune system

March 25, 2014
New research suggests that gut microorganisms do not merely influence immune cell function, but also support the production of immune cells that form the first line of defense against infection. By understanding the mechanisms ...

Lung lesions of TB variable, independent whether infection is active or latent

December 15, 2013
The lung lesions in an individual infected with tuberculosis (TB) are surprisingly variable and independent of each other, despite whether the patient has clinically active or latent disease, according to a new animal study ...

Improving newborns' bacterial environment could fend off infections, animal study suggests

April 20, 2014
Mothers give a newborn baby a gift of germs—germs that help to kick-start the infant's immune system. But antibiotics, used to fend off infection, may paradoxically interrupt a newborn's own immune responses, leaving already-vulnerable ...

Recommended for you

Hibernating ground squirrels provide clues to new stroke treatments

November 17, 2017
In the fight against brain damage caused by stroke, researchers have turned to an unlikely source of inspiration: hibernating ground squirrels.

Age and gut bacteria contribute to multiple sclerosis disease progression

November 17, 2017
Researchers at Rutgers Robert Wood Johnson Medical School published a study suggesting that gut bacteria at young age can contribute to multiple sclerosis (MS) disease onset and progression.

Molecular guardian defends cells, organs against excess cholesterol

November 16, 2017
A team of researchers at the Harvard T. H. Chan School of Public Health has illuminated a critical player in cholesterol metabolism that acts as a molecular guardian in cells to help maintain cholesterol levels within a safe, ...

Prototype ear plug sensor could improve monitoring of vital signs

November 16, 2017
Scientists have developed a sensor that fits in the ear, with the aim of monitoring the heart, brain and lungs functions for health and fitness.

Ancient enzyme could boost power of liquid biopsies to detect and profile cancers

November 16, 2017
Scientists are developing a set of medical tests called liquid biopsies that can rapidly detect the presence of cancers, infectious diseases and other conditions from only a small blood sample. Researchers at The University ...

FDA to crack down on risky stem cell offerings

November 16, 2017
U.S. health authorities announced plans Thursday to crack down on doctors pushing stem cell procedures that pose the gravest risks to patients amid an effort to police a burgeoning medical field that previously has received ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.