Microbiota therapeutics for inflammatory bowel disease: the way forward.

Microbiota therapeutics that transplant faecal material from healthy donors to people with mild-to-moderate ulcerative colitis have shown the potential to induce remission in about 30% of participants in small, phase 2 clinical trials. Despite this substantial achievement, the field needs to leverage the insights gained from these trials and progress towards phase 3 clinical trials and drug approval, while identifying the distinct clinical niche for this new therapeutic modality within inflammatory bowel disease (IBD) therapeutics. We describe the lessons that can be learned from past studies of microbiota therapeutics, from full spectrum donor stool to defined products manufactured in vitro. We explore the actionable insights these lessons provide on the design of near-term studies and future trajectories for the integration of microbiota therapeutics in the treatment of IBD. If successful, microbiota therapeutics will provide a powerful orthogonal approach (complementing or in combination with existing immunomodulatory drugs) to raise the therapeutic ceiling for the many non-responders and partial responders within the IBD patient population.

Ectoines as novel anti-inflammatory and tissue protective lead compounds with special focus on inflammatory bowel disease and lung inflammation.

The compatible solute ectoine is one of the most abundant and powerful cytoprotectant in the microbial world. Due to its unique ability to stabilize biological membranes and macromolecules it has been successfully commercialized as ingredient of various over-the-counter drugs, achieving primarily epithelial protection. While trying to elucidate the mechanism of its cell protective properties in in-vitro studies, a significant anti-inflammatory effect was documented for the small molecule. The tissue protective potential of ectoine considerably improved organ quality during preservation. In addition, ectoine and derivatives have been demonstrated to significantly decrease inflammatory cytokine production, thereby alleviating the inflammatory response following organ transplantation, and launching new therapeutic options for pathologies such as Inflammatory Bowel Disease (IBD) and Chronic Obstructive Pulmonary Disease (COPD). In this review, we aim to summarize the knowledge of this fairly nascent field of the anti-inflammatory potential of diverse ectoines. We also point out that this promising field faces challenges in its biochemical and molecular substantiations, including defining the molecular mechanisms of the observed effects and their regulation. However, based on their potent cytoprotective, anti-inflammatory, and non-toxic properties we believe that ectoines represent promising candidates for risk free interventions in inflammatory pathologies with steeply increasing demands for new therapeutics.

Boosting Escherichia coli's heterologous production rate of ectoines by exploiting the non-halophilic gene cluster from Acidiphilium cryptum.

The compatible solutes ectoine and hydroxyectoine are synthesized by many microorganisms as potent osmostress and desiccation protectants. Besides their successful implementation into various skincare products, they are of increasing biotechnological interest due to new applications in the healthcare sector. To meet this growing demand, efficient heterologous overproduction solutions for ectoines need to be found. This study is the first report on the utilization of the non-halophilic biosynthesis enzymes from Acidiphilium cryptum DSM 2389T for efficient heterologous production of ectoines in Escherichia coli. When grown at low salt conditions (≤ 0.5% NaCl) and utilizing the cheap carbon source glycerol, the production was characterized by the highest specific production of ectoine [2.9 g/g dry cell weight (dcw)] and hydroxyectoine (2.2 g/g dcw) reported so far and occurred at rapid specific production rates of up to 345 mg/(g dcw × h). This efficiency in production was related to an unprecedented carbon source conversion rate of approx. 60% of the theoretical maximum. These findings confirm the unique potential of the here implemented non-halophilic enzymes for ectoine production processes in E. coli and demonstrate the first efficient heterologous solution for hydroxyectoine production, as well as an extraordinary efficient low-salt ectoine production.