This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: An interdisciplinary team of researchers from UConn and the University of Pittsburgh is filling knowledge gaps about the surprising roles that our microbiomes play in our health. The team's recent studies, published in Gastro Hep Advances and The Journal of Physiology, focus on Bacteroidota species that grow in our guts and mouths, where they produce glycine lipids that interact with our metabolism.
The researchers found that microbiome-derived glycine lipids circulate systemically and improve mitochondrial function, which may prevent the progression of metabolic-dysfunction steatotic liver disease (MASLD) and regulate mitochondrial functioning in skeletal muscle tissue. While lipids produced by bacteria are usually associated with disease-causing processes, in 2022 members of the team—including Dr. Frank Nichols, professor of periodontology in the UConn School of Dental Medicine, Dr.
Robert Clark, professor in the Department of Immunology in UConn School of Medicine, and Department of Nutritional Sciences associate professor Christopher Blesso—published their findings showing that these lipids acted like signals that had an immunosuppressive effect in the development of atherosclerosis and liver inflammation. "Based on previous research, we expected that microbial glycine lipids would be pro-inflammatory and they'd worsen the disease. What we saw was the opposite and that surprised us," says Blesso.
To look closer at the impacts on the liver, the researchers focused on the glycine lipids' influence on MASLD. MASLD is a common form of liver disease, impacting around 30% of the adult population, and the treatment options are limited. Using a chronic liver disease mouse model, the researchers induced the progression of MASLD by feeding mice a high-fat, high-sugar diet simulating a typical Western diet.
The mice gained weight, accumulated fat in their livers and developed inflammation, Blesso explains. Then the researchers administered one of two microbial glycine lipids of interest. "(In our previous research) lipid 654 (L654) attenuated some of the liver injury, and then this other lipid is the newest lipid that Nichols has identified, called lipid 1256 (L1256) that is more potent at least in vitro than L654," says Blesso.
"The mice were getting one-microgram injections every other day for eight weeks, and then we looked at the disease process." Looking at the morphology and histopathology of the liver samples with the help of Department of Pathobiology and Veterinary Science associate professor Neha Mishra, they determined that both L654 and L1256 significantly attenuated the disease severity. The researchers also measured gene regulation and found an enhancement of genes that control mitochondrial biogenesis and fat oxidation, which helped protect against the progression of MASLD. "We found that if you deplete the exposure to these microbial glycine lipids, it enhances inflammation," says Blesso.
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