Research Roundup: New Insights into Crohn’s Disease and More

Research

Every week there are numerous scientific studies published. Here’s a look at some of the more interesting ones.

The Connection Between the Microbiome and Crohn’s Disease

The microbiome is the trillions of microorganisms that live in the body. Increasingly, the microbiome is being found to have an influence on a variety of diseases, not just of the gastrointestinal tract. Researchers at the University of Pennsylvania, working on the microbiomes of dogs, evaluated the connection between a prescription diet, the gut microbiome, and disease remission in Crohn’s in dogs. They published their research in the journal Microbiome.

“The bacteria in the gut are known to be a really important factor in tipping the scales toward disease,” stated Daniel Beiting, senior author of the study and an assistant professor in Penn’s School of Veterinary Medicine. “And the environmental factor that seems to contribute the most to rapid changes in the microbiome is what you eat. Given that dogs’ microbiomes are extremely similar to those of humans, we thought this was an intriguing model to ask, ‘Could diet be impacting this disease through an impact on the microbiome?’”

They treated a population of pet dogs that had canine chronic enteropathy (CE), which has similar symptoms as Crohn’s—weight loss, gut inflammation, diarrhea, occasional vomiting, loss of appetite. They collected stool samples at the beginning of the study and periodically through the study. They used genetic sequencing to catalog the microbes present as well as the metabolic products in the stools. This provided a functional read-out of the microbiome. On the diet, 20 of the 29 dogs went into remission. The genomic and metabolite analysis showed specific changes in those dogs; particularly, the ones that responded to the diet have increased secondary bile acids which are produced when specific gut microbes consume bile released by the liver. They then identified the “good” microbes that produce secondary bile acids, such as Clostridium hiranonis.

They found in working with a dataset of children with Crohn’s disease who were treated with a specialized liquid diet, that the children who responded to the therapy best had increased numbers of the bacteria species Clostridium scindens, which is a potent producer of secondary bile acids. “This study has greatly improved our knowledge of pediatric IBD and will lead to new therapies for children suffering with this disease,” said Robert N. Baldassano, study co-author and pediatric gastroenterologist at Children’s Hospital of Philadelphia.

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Protective Proteins Found Associated with Lower Blood Sugar in Type 2 Diabetes

Patients with type 2 diabetes who have high levels of IL-36 cytokines have lower blood sugar levels, suggesting that those proteins are linked to better blood glucose levels. IL-36 cytokines are part of the interleukin-1 family, which are implicated in the development of obesity-related diseases. At their root, these patients with type 2 diabetes appeared to have better control of their blood sugar levels than type 2 diabetes patients without them.

New Drug May Protect Against Memory Loss and Nerve Damage in Alzheimer’s

Researchers with the University at Buffalo and Tetra Therapeutics have identified a drug, BPN14770, that in preclinical research prevents amyloid-beta’s effects on the nervous system. Beta-amyloid is linked to Alzheimer’s disease, although its role is no longer as clear as was once thought. The drug appears to activate mechanisms that support nerve health and prevent dementia. It appears to activate phosphodiesterase 4D (PDE4D), an enzyme involved in memory formation, learning, neuroinflammation and traumatic brain injury.

New Technique IDs Brain Cell Structure and Epigenetics Simultaneously

Researchers with the Salk Institute combined two separate analytical techniques to analyze how epigenetics affects certain types of brain cells. The technique is called single-nucleus methyl-3C sequencing (sn-m3C-seq). This allowed the scientists to identify gene regulatory machinery in specific cell types but may also lead the way to understanding how some cells malfunction to cause disease. The Salk researchers’ approach allowed for the differentiation of cell types based on the structure of the chromosomes and simultaneously determining the methylation patterns. Previously the two approaches were separate, which made it difficult or impossible to determine how chromosome structure and methylation patterns were related.

Gene Therapy for Inherited Blindness Requires Good Timing

In 2017, the FDA approved Spark Therapeutics’ Luxturna, a gene therapy for biallelic RPE65 mutation-associated retinal dystrophy, a rare, genetic form of blindness. The company was acquired by Roche in 2019. Researchers recently conducted work on dogs with the therapy to determine more information about when the therapy is most appropriate and effective. Earlier research had suggested that, at least in dogs, if you gave the treatment when the retina was deteriorating, that deterioration would continue. So even though the therapy would provide relief, the disease would continue to progress. The research found that, in dogs at least, the therapy could be given when more than 63% of photoreceptor cells remained and the therapy was long-lasting, but below that threshold, the disease continued.

The Genetics Behind Flu-Related Heart Complications

Individuals with severe cases of the flu sometimes develop life-threatening heart problems, even when they were otherwise previously healthy. Researchers have a better understanding why now. In mice, they identified mutations in a gene called IFITM3 which is known to increase the risk of flu hospitalizations and deaths. The gene codes for a protein critical to the human immune response, especially for preventing the invasion of viruses. By knocking out the gene in mice and infecting them with the flu, they found that the lack of the gene increased the odds of heart abnormalities and death.

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