Scientists identify mechanisms driving gut bacterial imbalance and inflammation

February 8, 2017, UT Southwestern Medical Center
(From left are) Elizabeth Hughes, Dr. Sebastian Winter, and Maria Winter. Credit: UT Southwestern

A study led by UT Southwestern Medical Center researchers has uncovered key molecular pathways behind the disruption of the gut's delicate balance of bacteria during episodes of inflammatory disease.

"A deeper understanding of these pathways may help in developing new prevention and treatment strategies for conditions such as (IBD) and certain gastrointestinal infections and colorectal cancers," said Dr. Sebastian Winter, Assistant Professor of Microbiology and a W.W. Caruth, Jr. Scholar in Biomedical Research at UT Southwestern, who led the study.

More than 1 million people in the U.S. suffer from IBD, a chronic, lifelong inflammatory disorder of the intestines that has no cure or means of prevention.

The findings, published online today in Cell Host & Microbe, explain a critical mechanism behind the changes in the gut during , an issue that had previously been unclear to scientists.

"We found that correlates with a change in the nutrients available to the bacteria," said Elizabeth Hughes, a graduate student in the Winter Lab and co-first author of the study.

A healthy human gut is teeming with microbes, with bacterial cells outnumbering other cells in the body by 10-to-1. For most of a person's life, these microbial communities, or microbiota, facilitate digestion, protect against infections, and orchestrate the development of a healthy immune system.

During episodes of intestinal inflammation - which can occur during IBD and gastrointestinal infections and cancers - the composition of these gut microbial communities is radically disturbed.

"Beneficial bacteria begin to dwindle in numbers as less beneficial, or even harmful, bacteria flourish," said Ms. Hughes. "This imbalance of microbiota is believed to exacerbate the inflammation."

A healthy gut is devoid of oxygen. The beneficial bacteria that live there are well-adapted to the low-oxygen environment and break down fiber through fermentation. Unlike these , potentially harmful E. coli grow better in high-oxygen environments.

"Inflammation changes the environment so that it is no longer perfect for the commensal anaerobes, but perfect for opportunistic E. coli, which basically wait for an 'accident' like inflammation to happen," Dr. Winter explained.

The increased availability of oxygen during inflammation helps E. coli thrive in an inflamed gut through a metabolic "trick," Ms. Hughes said.

"Through respiration, the abundant waste products generated by the beneficial microbes can be 'recycled' by commensal E. coli - which do not grow well on fiber - and turned into valuable nutrients, thus fueling a potentially harmful bloom of the E. coli population," she explained.

Learning more about the forces behind disease-related shifts in the gut's bacterial composition provides insights into treatment targets and diagnostic resources. This understanding could lead to more effective treatments for IBD and inflammation-associated . New drugs might, for example, inhibit this particular metabolic function of E. coli.

"If we interfere with the production of waste products by the beneficial commensal bacteria, then we impede their metabolism, which causes them to grow more slowly and throw off the entire ecosystem," Dr. Winter said. "The most effective strategy may be to inhibit commensal E. coli's unique metabolism to avoid the bloom and negative impacts."

Dr. Winter and his research team continue to study these mechanisms.

Explore further: Scientists find key to growth of 'bad' bacteria in inflammatory bowel disease

More information: Cell Host & Microbe, DOI: 10.1016/j.chom.2017.01.005

Related Stories

Scientists find key to growth of 'bad' bacteria in inflammatory bowel disease

February 7, 2013
(Medical Xpress)—Scientists have long puzzled over why "bad" bacteria such as E. coli can thrive in the guts of those with inflammatory bowel disease (IBD), causing serious diarrhea. Now UC Davis researchers have discovered ...

Immune cells' bacteria may fight chronic inflammation

March 17, 2016
A population of bacteria inhabits human and mouse immune cells and appears to protect the body from inflammation and illness, Weill Cornell Medicine scientists discovered in a new study. The findings challenge conventional ...

Research finding could lead to targeted therapies for inflammatory bowel diseases

November 19, 2015
UT Southwestern Medical Center researchers have shown that a pathogen-sensing molecule plays a vital role in keeping gastrointestinal (GI) systems healthy.

Research explains how we live in harmony with friendly gut bacteria

January 9, 2015
Stability in the composition of the hundred trillion bacterial cells in the human gastrointestinal tract is crucial to health, but scientists have been perplexed how our microbiota withstands an onslaught of toxins, dietary ...

Antimicrobial found to calm inflamed gut in mice

November 1, 2016
(Medical Xpress)—A team of researchers with the University of California has found that introducing a type of antimicrobial protein called a microcin into the guts of mice with inflamed bowels caused a reduction in the ...

Gut pathogens thrive on body's tissue-repair mechanism

September 16, 2016
Why do some foodborne bacteria make us sick? A paper published Sept. 16 in the journal Science has found that pathogens in the intestinal tract cause harm because they benefit from immune system responses designed to repair ...

Recommended for you

Discovery opens door for synthetic opioids with less addictive qualities

June 1, 2018
Making opioids from sugar instead of from field grown opium poppies has the potential to solve many of the problems associated with manufacturing strong pain killers.

US doctors prescribing fewer opioid painkillers: report

May 31, 2018
US doctors reduced the number of prescriptions for opioid painkillers last year, continuing a five-year trend, in an effort to reverse a deadly drug abuse epidemic, a report released Thursday said.

Researchers publish study on new therapy to treat opioid use disorder

May 22, 2018
Better delivery of medications to treat opioid use disorder (OUD) is key to addressing the opioid crisis and helping the 2.6 million Americans affected by the disease.

Could nonprofit drug companies cut sky-high prices?

May 17, 2018
(HealthDay)—Generic prescription drugs should be cheap, but prices for some have soared in the United States in recent years. Now a group of U.S. hospitals thinks it has a solution: a nonprofit drug maker.

Fewer antibiotics for kids, but more ADHD drugs

May 15, 2018
(HealthDay)—American kids are taking fewer prescription medications these days—but certain drugs are being prescribed more than ever, a new government study finds.

Opioid makers' perks to docs tied to more prescriptions

May 14, 2018
Doctors who accept perks from companies that make opioid painkillers are more likely to prescribe the drugs for their patients, new research suggests.

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.