Metformin is recognized as the best choice for initial treatment of hyperglycemia in patients with type 2 diabetes mellitus having several advantages over other types of anti-diabetic medications. However metformin is widely described as poorly tolerated due to gastrointestinal tract (GIT) side effects. Our previous studies have shown that metformin treatment induces shifts in the taxonomic and functional profile of the gut microbiome. It is observed that co-administration of probiotics with metformin has shown beneficial effects on reducing GIT side effects of metformin. In addition to probiotics, prebiotics such as polyherbal formulations are also widely considered in the treatment of GIT dysbiosis. The project is based on the hypothesis that a polyherbal formulation as an add-on treatment has the ability to improve the outcome of conventional antidiabetic therapy by targeting the composition of the gut microbiome. The overall aim of this project is to evaluate the effects of interactions between metformin and traditionally used polyherbal formulations on gut microbiota in a prospective crossover study involving type 2 diabetes mellitus patients. We suppose that the study will bring forward an alternative approach to impact the gut microbiome by polyherbal formulation providing a more effective clinical use. It is expected that the implementation of the project will advance the development of drug-supplementary-based solutions for the treatment of metabolic disease

Periodontal diseases (PDD) are one of the most common diseases, affecting up to 90% of adults during their life, but 11% develop severe-type periodontitis (PD). P.gingivalis (Pg) is proposed as a major etiologic agent and keystone pathogen of PD. PD is associated with rheumatoid arthritis, atherosclerotic cardiovascular disease, diabetes, Alzheimer, Parkinson\\\'s disease, and certain cancers. Peptidylarginine deiminase (PPAD) is a critical virulence factor of Pg - an enzyme that citrullinates Pg proteins, changing conformation and function and ensuring maturation. PPAD also citrunillate host proteins - identified in inflammatory arthritis, multiple sclerosis, glaucoma, psoriasis, myositis, and sporadic Creutzfeldt-Jakob disease. Immunization against Pg various antigens had demonstrated the production of specific antibodies (Abs), reduction of bone mass loss, and any recognizable side effects. The main goal of this project is to develop a prototype PPAD-targeted therapeutic vaccine for therapy and prevention of Pg-caused PD and its caused systemic conditions. To achieve the set goal - a vaccine prototype will be created, based on plant VLPs, containing PPAD on the surface as a target antigen for neutralizing Ab development. Vaccine immunogenicity test will be done in mice by determining Ab titers, classes, avidity by ELISA, testing in cell cultures, and WB. The efficacy of the prototype will be tested in a mouse disease model, monitoring disease progression.

Celiac Disease (CeD) is incurable autoimmune disorder that affects the small intestine and is caused by gluten, barley and rye ingestion. CeD has a strong genetic component as individuals carring HLA-DQ2 or HLA-DQ8 variant have a higher risk of developing the disease. It is more common in individuals with familial history of the disease. When CeD patient consumes gluten, their immune system reacts by attacking the lining of the intestine, leading to inflammation and damage of the villi. Unfortunately, there are no human based in vitro models for CeD and only one mouse model available. Therefore, we aim to model the pathogensis of CeD by using patient derived induced pluripotent stem cells (iPSC) in CeD on a PDMS-free organ chip (CDOC) through the following tasks: reprogramming patient and healthy donor somatic cells into iPSC, differentiate patient and healthy donor derived iPSC into intestinal organoids and endothelial cells and seed them on the chip in a co-culture with patient peripheral blood mononuclear cells and evaluate the villious stuctures during co-culture. After the model is established pathogenesis will be induced with gluten and disease model and healthy villi structures will be evaluated by immunofluorescence, gut barrier integrity measurments and cytokine secretion. The establishment of CDOC will give a model for future development of drugs and treatment of CeD and a better understanding of the disease ethiology