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After finding high levels of corisin — a small peptide produced by Staphylococcus bacteria in the gut — in the blood of patients with diabetic kidney fibrosis, the researchers used computer simulations and tissue and mouse experiments to track how corisin affects the kidneys, how it gets there from the gut, and a possible method of countering it with antibody treatment.

“Our earlier studies showed corisin can damage cells and worsen tissue scarring and fibrosis in other organs, so we suspected it might be a hidden driver of kidney fibrosis,” said Illinois animal sciences professor Isaac Cann, who led the study with Mie University immunology professor Dr. Esteban Gabazza. Cann and Gabazza are affiliates of the Carl R. Woese Institute for Genomic Biology at Illinois. “Our new findings suggest corisin is indeed a hidden culprit behind progressive kidney damage in diabetes, and that blocking it could offer a new way to protect kidney health in patients.”

The researchers published their findings in the journal Nature Communications.

Diabetic kidney fibrosis is a major cause of kidney failure worldwide, yet the key drivers of it have remained a mystery, and no treatments can stop the process, said Dr. Taro Yasuma of Mie University, a medical doctor and the first author of the manuscript.

“Many people with longstanding diabetes eventually develop kidney fibrosis, and once it progresses, there are limited options beyond dialysis or kidney transplantation. Current treatments mainly focus on controlling blood sugar and blood pressure, but there’s no cure that stops or reverses the scarring or fibrotic process,” Yasuma said.

The researchers began by screening the blood and urine of patients with diabetic kidney disease. They found that patients had significantly more corisin than their healthy counterparts, and that the amount of corisin in the blood correlated with the extent of kidney damage.

Upon seeing the same results in mice with kidney fibrosis, the researchers tracked what corisin was doing in the kidneys of the mice. They found that corisin speeds up aging in kidney cells, setting off a chain reaction from inflammation to cell death to a buildup of scar tissue, eventually resulting in the loss of kidney function and worsening fibrosis.

But how was corisin getting from the gut to the kidneys? Cann and Gabazza’s groups collaborated with U. of I. chemical and biomolecular engineering professor Diwakar Shukla’s group to produce computer simulations and laboratory experiments to follow corisin’s journey from the gut to the bloodstream. They found that corisin can attach to albumin, one of the most common proteins in blood, and ride it through the bloodstream. When it reaches the kidneys, corisin detaches from the albumin to attack the delicate structures that filter blood and urine.

To confirm that corisin was the main culprit behind the kidney damage, the researchers gave the mice antibodies against corisin. They saw a dramatic reduction in the speed of kidney damage.

“When we treated the mice with an antibody that neutralizes corisin, it slowed the aging of kidney cells and greatly reduced kidney scarring,” said Gabazza, who also is an adjunct professor of animal sciences at Illinois. “While no such antibody is currently approved for use in humans, our findings suggest it could be developed into a new treatment.”

Next, the researchers plan to test anticorisin treatments in more advanced animal models, such as pigs, to explore how they could be adapted for safe use in humans. The U. of I. and Mie University have a joint invention disclosure on corisin antibodies.

“Our work suggests that blocking corisin, either with antibodies or other targeted therapies, could slow down or prevent kidney scarring in diabetes and thus enhance the quality of life for patients,” Cann said.

This study was supported by the Japan Science and Technology Agency, the Japan Society for the Promotion of Science, the Takeda Science Foundation, the

Japan Association for Diabetes Education and Care, the Eli Lilly Japan Innovation Research Grant, the Daiwa Security Foundation and the Charles and Margaret Levin Family Foundation. Cann is also a professor of microbiology and nutritional sciences and a member of the Center for East Asian and Pacific Studies at Illinois.

A collaborative research team led by Professor Jang Hyun Choi from the Department of Life Sciences at UNIST, in partnership with Professor Hwayoung Yun from the College of Pharmacy and Research Institute for Drug Development at Pusan National University (PNU), and Professor Neung Hwa Park from Ulsan University Hospital (UUH), has, for the first time globally, elucidated the role of microRNA-93 (miR-93), which is expressed in the liver, as a key genetic regulator in the development and progression of MASLD.

MiR-93 is a specialized RNA molecule expressed in hepatocytes that functions to suppress the expression of specific target genes. The team observed abnormally elevated levels of miR-93 in both patients with fatty liver disease and animal models. Through molecular analysis, they demonstrated that miR-93 promotes lipid accumulation, inflammation, and fibrosis by inhibiting the expression of SIRT1, a gene involved in lipid metabolism within liver cells.

In experiments utilizing gene editing techniques to eliminate miR-93 production in mice, researchers observed a marked reduction in hepatic fat accumulation, along with significant improvements in insulin sensitivity and liver function indicators. Conversely, mice with overexpressed miR-93 exhibited worsened hepatic metabolic function.

Furthermore, screening 150 FDA-approved drugs revealed that niacin (vitamin B3) most effectively suppresses miR-93. Mice treated with niacin showed a significant decrease in hepatic miR-93 levels and a notable increase in SIRT1 activity. The activated SIRT1 restored disrupted lipid metabolism pathways, thereby normalizing liver lipid homeostasis.

The research team explained, “This study precisely elucidates the molecular origin of MASLD and demonstrates the potential for repurposing an already approved vitamin compound to modulate this pathway, which has high translational clinical relevance.”

They added, “Given that niacin is a well-established and safe medication used to treat hyperlipidemia, it holds promise as a candidate for combination therapies targeting miRNA pathways in MASLD.”

This research was supported by various including the National Research Foundation of Korea (NRF) and the Korea Research Institute of Bioscience and Biotechnology (KRIBB). The findings were published online in the prestigious biomedical journal, Metabolism: Clinical and Experimental. Participants include Dr. Yo Han Lee and Kieun Park from UNIST, along with Professor Joonho Jeong from Ulsan University Hospital and Jinyoung Lee from Pusan National University, as co-first authors.