Breaking News
May 27, 2018 - Breast cancer survivors do not receive recommended level of screening after surgery
May 27, 2018 - Recommendations Developed for Managing Postpartum Pain
May 27, 2018 - Rheumatoid Arthritis (RA) | Arthritis Basics | Arthritis Types | Arthritis
May 27, 2018 - ‘Life support’ for transplant livers better than freezing: study
May 27, 2018 - Tree nut consumption linked to improved type 2 diabetes health
May 27, 2018 - Income and education gap causes racial differences in health behaviors, study shows
May 27, 2018 - Even at ‘Safe’ Levels, Air Pollution Puts Seniors at Risk
May 27, 2018 - Obstructive sleep apnea linked to thinning of calvaria, skull base
May 27, 2018 - Epigem’s Managing Director sets the bar for life sciences industry at VentureFest
May 27, 2018 - CPAP may reduce resting heart rate in prediabetic patients
May 27, 2018 - Study reveals striking disparities in health care access and quality across most nations
May 27, 2018 - The Yogi masters were right—meditation and breathing exercises can sharpen your mind
May 27, 2018 - SLU researcher aims to find solutions for diabetes patients at risk of hypoglycemia
May 27, 2018 - Scientists uncover the cause of insulin resistance in obesity
May 27, 2018 - $2.3 million NIH grant to support new project on oxytocin neurons and social behavior
May 27, 2018 - Less Driving Tied to Lower Cardiovascular Disease Risk
May 27, 2018 - Genetics Home Reference: LMNA-related congenital muscular dystrophy
May 27, 2018 - Long-term psychological study confirms time is the best medicine against homesickness
May 27, 2018 - Study explores if CPAP treatment can improve sexual QOL for sleep apnea patients
May 27, 2018 - Study investigates role played by brain in prosocial behavior
May 27, 2018 - New Guidelines Mean 1 in 3 Adults May Need Blood Pressure Meds
May 27, 2018 - Cerebrospinal Fluid (CSF) Analysis: MedlinePlus Lab Test Information
May 27, 2018 - Kids in tough neighborhoods head to ER more often
May 27, 2018 - Exercise alters brain’s dopamine system to help treat addiction, study finds
May 27, 2018 - Sepsis patients treated and released from ED for outpatient follow-up experience good outcomes
May 27, 2018 - Initiative cuts overuse of tests, treatments for bronchiolitis
May 27, 2018 - Study links ‘sleep spindles’ to memory reactivation
May 27, 2018 - Scientists develop new method to speed up genome evolution of baker’s yeast
May 27, 2018 - Sunscreen pills are fake says FDA
May 27, 2018 - Study finds increasing wealth gap between households of seniors and families with children
May 27, 2018 - Link between tuberculosis and Parkinson’s disease discovered
May 27, 2018 - Doctors call on health authorities for permission to provide stroke patients with life-saving treatment
May 26, 2018 - Couples who eat seafood-rich diet tend to get pregnant faster
May 26, 2018 - NIH summit presents recommendations to accelerate treatment development for Alzheimer’s disease
May 26, 2018 - Medication-related harm found to be common among older adults, but preventable
May 26, 2018 - Lunaphore and Vitro announce partnership to develop ISH protocols for RNA, DNA targets
May 26, 2018 - Cryoablation Efficacious for Cancer Pain, Review Finds
May 26, 2018 - Link between IBD and Parkinson’s might allow doctors to slow down condition
May 26, 2018 - Study finds fewer than 5% of low-income, urban mothers use prenatal vitamins before pregnancy
May 26, 2018 - California hospitals urge moms to favor breast milk over formula
May 26, 2018 - Most concussion patients do not receive follow-up care after hospital discharge, says study
May 26, 2018 - Lifetime risks of developing Alzheimer’s dementia vary by age, gender
May 26, 2018 - Researchers find novel ways to improve participation in clinical research
May 26, 2018 - Researchers develop methods for measuring free-base nicotine levels in e-cigarettes
May 26, 2018 - AHA: Preterm Birth Could Warn of Mom’s Future Heart Risks
May 26, 2018 - Some calories more harmful than others
May 26, 2018 - Study links cell size with commitment to division
May 26, 2018 - Researchers develop new, rapid blood test to detect liver damage
May 26, 2018 - Researchers discover cascade of immune processes linked to poor outcomes in aggressive breast cancer
May 26, 2018 - New research will use mathematics to solve mysteries in cell biology
May 26, 2018 - Proposed National Resilience Strategy to reverse catastrophic increases in ‘deaths of despair’
May 26, 2018 - Mice remain slim on burger diet
May 26, 2018 - BMC receives $13.5 million award to test methods for delivering childhood anxiety treatment
May 26, 2018 - ‘Right to Try Act’ will not benefit terminally-ill patients
May 26, 2018 - Study reveals novel statistical algorithm to identify potential disease genes
May 26, 2018 - Two genes play vital roles in malignant brain cancer
May 26, 2018 - Study explores link between groundwater lithium and diagnoses of bipolar disorder, dementia
May 26, 2018 - Researchers reveal stimulatory effects of myelin on young neural cells
May 26, 2018 - Small part of cellular protein that helps form long-term memories also drives neurodegeneration
May 26, 2018 - Four-legged friends can have heart issues, too
May 26, 2018 - Scientists create small, self-contained spaces inside mammalian cells
May 26, 2018 - Better Social Support Network Protects Black Men Against HIV
May 26, 2018 - National Heart, Lung, and Blood Institute (NHLBI)
May 26, 2018 - Burnout, depression can affect ophthalmology residents, study finds
May 26, 2018 - Latinos and African Americans more likely to experience serious depression than Whites
May 26, 2018 - Data from past epidemic could help improve response to future Ebola outbreaks
May 26, 2018 - Researchers provide insight into how the memory molecule limits brain plasticity
May 26, 2018 - OSU biologist describes ‘restoration ecology’ approach toward patient health
May 26, 2018 - New approach to study brown fat could aid in finding treatments for obesity
May 26, 2018 - UCI Center on Stress & Health receives NIH funding to develop digital health interventions
May 26, 2018 - Could More Fish in the Diet Boost Sex Lives and Fertility?
May 26, 2018 - NTU Singapore and SERI invent new scope to diagnose glaucoma
May 26, 2018 - Cancer cells co-opt pain-sensing ‘neural channel’ to increase tolerance against oxidative stress
May 26, 2018 - Study uncovers why pesticide exposure increases Parkinson’s disease risk in some people
May 26, 2018 - Study finds link between lead exposure and fertility rates
May 26, 2018 - Causes and treatment of acute heart failure vary by region, registry shows
May 26, 2018 - Delivery of standardized diabetes care could help achieve equitable health outcomes for all patients
May 26, 2018 - FDA authorizes marketing of OsteoDetect software for detecting wrist fractures
May 26, 2018 - HSE experts suggest new way of looking at infantilism
May 26, 2018 - Children and adolescents growing up in extreme societal conditions more likely to resort to violence
Engineering the gut microbiome with ‘good’ bacteria may help treat Crohn’s disease

Engineering the gut microbiome with ‘good’ bacteria may help treat Crohn’s disease

image_pdfDownload PDFimage_print
Researchers revealed new insight about how gut bacteria contribute to Crohn’s disease. Credit: Chris Bickel

Penn Medicine researchers have singled out a bacterial enzyme behind an imbalance in the gut microbiome linked to Crohn’s disease. The new study, published online this week in Science Translational Medicine, suggests that wiping out a significant portion of the bacteria in the gut microbiome, and then re-introducing a certain type of “good” bacteria that lacks this enzyme, known as urease, may be an effective approach to better treat these diseases.

“Because it’s a single enzyme that is involved in this process, it might be a targetable solution,” said the study’s senior author, Gary D. Wu, MD, associate chief for research in the division of Gastroenterology at the Perelman School of Medicine at the University of Pennsylvania. “The idea would be that we could ‘engineer’ the composition of the microbiota in some way that lacks this particular one.”

An imbalance in the gut microbiome – more “bad” bacteria than “good” – is known as dysbiosis, which is caused by environmental stressors, such as intestinal inflammation, antibiotics, or diet. Gut dysbiosis is believed to fuel Crohn’s disease and other diseases, but the mechanisms behind that relationship is not fully understood by researchers looking to strike a healthier, bacterial balance for patients. Crohn’s disease is an inflammatory bowel disease that affects nearly one million children and adults in the United States.

In a series of human and mouse studies, the researchers discovered that a type of “bad” bacteria known as Proteobacteria feeding on urea, a waste product that can end up back in the colon, played an important role in the development of dysbiosis.

The “bad” bacteria, which harbor the urease enzyme, convert urea into ammonia (nitrogen metabolism), which is then reabsorbed by bacteria to make amino acids that are associated with dysbiosis in Crohn’s disease. “Good” bacteria may not respond in a similar manner, and thus may serve as a potential therapeutic approach to engineer the microbiome into a healthier state and treat disease.

“The study is important is because it shows that the movement of nitrogen into bacteria is an important process in the development of dysbiosis,” Wu said. “It also proves using a single enzyme can reconfigure the entire composition of the gut microbiota.”

The research was conducted by Wu and colleagues from Penn Medicine and Children’s Hospital of Philadelphia (CHOP), under the PennCHOP Microbiome Program with funding from the Crohn’s and Colitis Foundation.

To investigate the role of nitrogen metabolism in dysbiosis, the researchers performed a metabolomic analysis characterizing small molecules in fecal samples from 90 patients with Crohn’s disease from the Pediatric Longitudinal Study of Elemental Diet and Stool Microbiota Composition (PLEASE) study and 26 healthy children.

The results showed that fecal amino acids, a result of bacterial nitrogen metabolism, were significantly associated with Crohn’s disease, dysbiosis, and an abundance of Proteobacteria in patients. That led the researchers to track nitrogen metabolism activity in the mouse models to help reveal mechanisms that might be targets for the treatment of disease.

To show that urease regulated bacterial nitrogen metabolism and leads to dysbiosis, the microbiome’s slate had to be wiped clean before the microbiota could be engineered into a specific configuration. Researchers previously showed pretreating mice with antibiotics (vancomycin and neomycin) and polyethylene glycol (PEG), an intestinal purging agent used by patients in preparation for a colonoscopy, significantly reduced the bacterial load enough to create an opportunity for a newly introduced bacterial community to establish themselves.

Using this approach, in the current study, researchers showed that inoculating pre-treated mice with a single bacterial species, Escherichia coli, altered the gut microbiome in a significant way, depending on the presence of urease. Mice injected with urease-negative E. coli did not lead to dysbiosis, while mice with urease-positive E. coli did. The urease-positive E. coli also exacerbated colitis in the mice.

Similar to mice, treating five human subjects with the same two antibiotics and PEG also successfully reduced bacterial load in their intestinal tract by 100,000-fold, suggesting that it might be possible to engineer the composition of the gut microbiota in patients with inflammatory bowel disease.

“Now that we can effectively reduce bacterial load in humans it may now be possible to engineer the microbiota into a different configuration in a manner similar to what we have achieved in mice,” Wu said. “Although we’re closer now, there is still more work to be done.”

In fact, the Penn and CHOP team are currently conducting a therapeutic clinical study in patients with refractory Crohn’s disease using a strategy based on data from this study that focuses on deeply altering the gut microbiota.

“The outcomes of this study and the analysis of collected biospecimens will be an important first step in building a technology platform to engineer a beneficial composition of the gut microbiota for the treatment of inflammatory bowel diseases,” Wu said.


Explore further:
New link found between gut bacteria and age-related conditions

More information:
J. Ni el al., “A role for bacterial urease in gut dysbiosis and Crohn’s disease,” Science Translational Medicine (2017). stm.sciencemag.org/lookup/doi/ … scitranslmed.aah6888

Journal reference:
Science Translational Medicine

Provided by:
Perelman School of Medicine at the University of Pennsylvania

Tagged with:

About author

Related Articles