The gut microbiota is a complex and diverse population of microorganisms, consisting of bacteria, viruses, and fungi that serve many purposes in the human body. Studies have shown that dysbiosis (imbalance) and/or a decreased diversity of intestinal microbial flora is directly correlated with numerous diseases, including inflammatory diseases. Ulcerative colitis, autoimmune hepatitis, and rheumatoid arthritis are among the inflammatory diseases that demonstrate a notable association and have shown promising responses to a treatment designed to enhance gut health, called Fecal Microbiota Transplant (FMT). FMT involves the transfer of fecal microbes from a healthy donor to an individual suffering from a specific disease. Through the compilation of scholarly sources, this project aims to provide a more in-depth understanding of the impact of the gut microbiota on inflammatory diseases and yield information as to why FMT is a promising course of action to treat the three diseases mentioned previously. While working to demystify the intricate interplay between gut microbiota and inflammatory diseases, this literature review will also offer insights on where researchers should focus their efforts to provide new methods of treatment, bringing hope to millions of individuals worldwide.

Aging is a universal physiological process that is a part of all living organisms. Aging is caused by structural changes to metabolic and signal transduction pathways. In order to understand the impact of these molecular structures we use model organism Caenorhabditis elegans (C. elegans), a transparent nematode roundworm which is characterized by having a short generation time and short lifespan, making it easy to manipulate and monitor for aging studies. In invertebrate model systems, hundreds of drugs have been found to prolong life. Each drug has a restricted range of targets and cannot, by itself, have a beneficial effect on the full range of molecular processes involved in aging. Combinations of pro-longevity drugs with additive or synergistic mechanistic targets may be more beneficial than using the drugs alone. In addition to drug combinations, we will be using an optimized testing device to observe and conduct analysis of C. elegans. We can more easily observe thousands of individual C. elegans with the WorMotel system when combined with automated imaging and analysis than with any manual experiment. Screening medication combinations to find additive or synergistic interactions can be improved due to this platform. Data is currently being collected and will be analyzed later this month. Our goal is to further understand the benefits of pro-longevity drug combinations on aging on C. elegans.

Tryptophan metabolism is linked to the development of autoimmunity, suggesting one of its active metabolites activates immune responses. Our own data utilizing a mouse model suggests a link between the tryptophan metabolite, indole, and autoimmune arthritis leading to the hypothesis that indole is pathogenic. The similarities in joint inflammation which develops in the mouse Collagen Induced Arthritis (CIA) model resembles inflammation in human patients. To investigate the effect of tryptophan metabolism and indole production, we devised 3 treatment groups to determine the effect/severity on inflammatory response during CIA model. DBA mice of six to eight weeks old were used in the experiment to ensure a fully mature immune system. Mice were immunized with complete Freund’s adjuvant (CFA) and collagen at day zero and day twenty-one, given formulated diets and indole, and scored for joint inflammation regularly. At day 35, serum was collected for analysis of anti-collagen autoantibody production by ELISA for anti-collagen Immunoglobulin G (IgG) and IgG isotypes (IgG1, IgG2a, and IgG 2b). Tryptophan produces indole by metabolic pathway and affects anti-CII antibodies, which then affects joint inflammation. Changing mice to a tryptophan deficient diet reduced auto-immune arthritis as C3 activation and IgG 2b was lower. Removal of indole (TD) from CIA mouse diets led to less pathology observed. The importance of this is to facilitate a better understanding which can translate to treatment for analogous human auto-immune arthritis and risk factors. This data also helps to highlight the role of diet and gut microbiota regarding those with predisposed conditions.