Body-gut bacteria partnerships may unlock cholesterol control and fatty liver treatments
New research suggests potential solutions to fatty liver disease and high cholesterol by revealing the workings of body-gut bacteria partnerships. According to the study, the partnerships balance complex chemicals regulating bile acids for digestion, cholesterol control, and fat metabolism.
Published in Nature, the research reveals that when gut bacteria produce bile acids that activate the farnesoid X receptor (FXR), the body counters this by producing bile acid-methylcysteamines (BA-MCYs), which help maintain metabolic balance.
Nutrition Insight speaks with the paper author, Frank Schroeder, a professor at Cornell University’s Boyce Thompson Institute, about how dietary changes, such as increasing fiber intake, could enhance BA-MCY production and offer new avenues for managing health issues.
Signaling molecules
Schroeder explains that bile acids don’t just help digest fats in the liver. They also act as signaling molecules to regulate fat and cholesterol levels.
“The textbook model of bile acid signaling puts the microbiota in charge: They produce free bile acids, which are agonists of a lynchpin regulator of cholesterol metabolism and fat storage — the nuclear receptor, FXR.”
“If the microbiota produces too many active free bile acids, cholesterol and fat metabolism can be negatively impacted. For example, fat can accumulate in the liver, which can then contribute to the development of non-alcoholic fatty liver disease,” he explains.
According to the study, a high-fiber diet has a strong positive impact on BA-MCY production. However, Schroeder says they cannot yet know which foods are best.
He explains that the gut and bile acid connection was not examined more closely before because BA-MCYs are more difficult to detect.
Gut bacteria produce bile acids that activate the FXR, which the body counters with BA-MCYs to help maintain metabolic balance.“Because, on the one hand, their mass spectroscopic properties make them look like artifacts derived from other, very well-known bile acid derivatives. In addition, the fact that BA-MCYs are produced in the host’s intestine, not the liver, like other host-derived bile acids, may have prevented their identification.”
Mice to human applications
Schroeder says there is a need to better understand how these compounds work in mice to determine what problems might arise when attempting to turn the research into treatments.
“Do they regulate overall body fat? Can BA-MCY supplementation decrease overall cholesterol levels? Are there positive implications for cardiovascular disease? Can BA-MCYs provide long-term benefits for liver health?”
He adds that the next step is to clarify how BA-MCY production is regulated in people, such as by determining how different diets and lifestyle factors affect BA-MCY production.
“Importantly, because the BA-MCYs occur naturally in the human body, the timeline to developing these compounds as drugs may be significantly shorter than other drug leads based on non-natural, purely synthetic compounds,” he continues.
According to Schroeder, his team will look into what dietary regimens might boost the production of BA-MCY if their mouse studies continue to show significant metabolic benefits, such as on liver fat levels and cholesterol metabolism. “Of course, this would have to be done in mouse models first, but subsequent human validation would be very straightforward.”
In recent developments, Nutrition Insight explored fiber-fortified product health benefits with professionals from Sensus, COMET, Tate & Lyle, Alland & Robert, and Ingredion.
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