At the University of Toronto, researchers have made an exciting discovery about the compounds naturally present in our gut.
They’ve found that these compounds can help reduce inflammation and improve symptoms related to various digestive problems by interacting with a crucial, yet not well-understood, part of our cells known as a nuclear receptor.
The gut microbiome, which is the community of bacteria living in our digestive system, produces these beneficial compounds as a side effect of breaking down what we eat.
These by-products have the ability to bind to nuclear receptors, which are vital for converting DNA information into proteins and other essential molecules in our body.
Jiabao Liu, a research associate at U of T’s Donnelly Centre for Cellular and Biomolecular Research and the first author of the study, explained their approach. “We conducted an unbiased screen of small molecules across the human gut microbiome,” Liu said.
This process led them to identify molecules that behave similarly to man-made compounds currently used to manage a specific nuclear receptor known as the constitutive androstane receptor, or CAR.
This receptor is key to how our liver handles foreign substances, including medications, and is involved in controlling inflammation in the intestines.
The findings, which were published in the journal Nature Communications, highlight the potential of these natural compounds for developing new drugs.
Henry Krause, the study’s principal investigator and a professor of molecular genetics at the Donnelly Centre and the Temerty Faculty of Medicine, noted the challenges of studying CAR.
“One issue with CAR is that we don’t have compounds that effectively bind to both human and mouse versions of the receptor,” Krause explained.
This compatibility is crucial for early research stages that involve animal models before human testing. Previous efforts have focused on creating synthetic activators that sometimes over-stimulate the receptor, causing unwanted effects.
However, the natural compounds identified by the Toronto team, named diindolylmethane (DIM) and diindolylethane (DIE), do not have these drawbacks.
Interestingly, while DIM was already known from previous studies, DIE was discovered for the first time in the human microbiome through this research.
Both compounds were able to regulate CAR effectively in liver cells from both humans and mice and matched the performance of a synthetic CAR activator known as CITCO, without causing side effects like liver enlargement in mice.
This breakthrough is particularly promising because it opens the door to using DIM and DIE in animal studies, which can then be translated into human treatments.
“This receptor is linked to several health issues, including diabetes, fatty liver disease, and ulcerative colitis in the small intestine,” Liu highlighted. With these natural compounds, there’s potential to treat these conditions more effectively.
By tapping into the therapeutic potential of compounds already present in our bodies, the researchers at the University of Toronto are paving the way for new, safer treatments for a range of digestive and metabolic diseases.
If you care about health, please read studies that vitamin D can help reduce inflammation, and vitamin K could lower your heart disease risk by a third.
For more information about health, please see recent studies about new way to halt excessive inflammation, and results showing foods that could cause inflammation.
The research findings can be found in Nature Communications.
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