• rAmuc_1100: A Novel Postbiotic Candidate Superior to Metformin in a Diabetic Mouse Model
  • Mahdi Pshgahi,1 Saeid Bouzari,2 Maryam Tajabadi Ebrahimi,3 Seyed Davar Siadat,4,*
    1. Science Department, Science and research Branch, Islamic Azad University, Tehran, Iran
    2. Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran
    3. Science Department, Science Faculty, Tehran Central Branch, Islamic Azad University, Tehran, Iran
    4. Department of Molecular Biology, Pasteur Institute of Iran, Tehran, Iran


  • Introduction: Akkermansia muciniphila, a gut bacterium known for degrading mucin, has recently attracted significant interest due to its positive metabolic effects in conditions such as obesity and type 2 diabetes mellitus (T2DM). Among the various bioactive molecules derived from this bacterium, the outer membrane protein Amuc_1100 stands out as a highly abundant component that may deliver therapeutic benefits independently of the live microorganism. This research focused on assessing the antidiabetic efficacy of the recombinant Amuc_1100 protein (rAmuc_1100) relative to metformin, extracellular vesicles (EVs), and live A. muciniphila in a mouse model simulating T2DM.
  • Methods: Following amplification, the gene encoding Amuc_1100 was cloned into an expression system and heterologously expressed in Escherichia coli. The recombinant protein was then purified using affinity chromatography techniques. Simultaneously, extracellular vesicles were isolated employing sequential ultrafiltration and ultracentrifugation protocols. Diabetes was induced in mice by administering nicotinamide and streptozotocin combined with a high-fat dietary regimen. The diabetic animals were subsequently distributed into six groups: untreated control, EVs, rAmuc_1100, metformin, a combination of rAmuc_1100 and metformin, and live A. muciniphila. Oral administration of respective treatments continued for 10 days. Blood glucose levels in both fasting and fed states were measured, and oral glucose tolerance tests (OGTT) were conducted to evaluate metabolic responses.
  • Results: Treatment with recombinant Amuc_1100 alone resulted in the most pronounced decrease in fasting and non-fasting blood glucose levels and notably enhanced glucose tolerance during OGTT (p < 0.0001). This effect exceeded that observed with metformin monotherapy, and no additive benefit was observed with combined treatment. Moderate glycemic improvements were observed in groups receiving EVs and live A. muciniphila.
  • Conclusion: The recombinant Amuc_1100 protein demonstrates strong antidiabetic potential, positioning it as a promising, well-characterized postbiotic candidate. These results endorse further exploration of rAmuc_1100 as a safe and effective alternative or adjunct therapy in managing T2DM.
  • Keywords: Akkermansia muciniphila, Extracellular vesicles, Amuc-1100, Diabetes Mellitus Type 2, Metformin.