Bacteria-Derived Compatible Solutes Ectoine and 5α-Hydroxyectoine Act as Intestinal Barrier Stabilizers to Ameliorate Experimental Inflammatory Bowel Disease

Abstract

Earlier studies showed that the compatible solute ectoine (1) given prophylactically before induction of colitis by 2,4,6-trinitrobenzenesulfonic acid (TNBS) in rats prevented histological changes induced in the colon and the associated rise in inflammatory mediators. This study was therefore conducted to investigate whether ectoine (1) and its 5α-hydroxy derivative (2) would also be effective in treating an already established condition. Two days after inducing colitis in rats by instilling TNBS/alcohol in the colon, animals were treated orally once daily for 1 week with either 1 or 2 (50, 100, 300 mg/kg). Twenty-four hours after the last drug administration rats were sacrificed. Ulcerative lesions and colon mass indices were reduced by 1 and 2 in a bell-shaped manner. Best results were obtained with 100 mg/kg ectoine (1) and 50 mg/kg 5α-hydroxyectoine (2). The solutes normalized the rise in myeloperoxidase, TNFα, and IL-1β induced by TNBS but did not affect levels of reduced glutathione or ICAM-1, while reducing the level of fecal calprotectin, an established marker for inflammatory bowel disease. The findings indicate that the naturally occurring compatible solutes ectoine (1) and 5α-hydroxyectoine (2) possess an optimum concentration that affords maximal intestinal barrier stabilization and could therefore prove useful for better management of human inflammatory bowel disease.

Exploring the Therapeutic Potential of Ectoine in Duchenne Muscular Dystrophy: Comparison with Taurine, a Supplement with Known Beneficial Effects in the mdx Mouse

“…To our knowledge, this is the first study describing weight loss in ectoine-treated mice. Previous studies have reported either no effect of ectoine on body weight or weight loss in experimental colitis, counteracted by ectoine treatment [ 21 , 44 ]. The mechanism by which ectoine might exert this effect remains unknown and needs further investigation.…”

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

“…While ectoine lowers the melting temperature of double-stranded DNA, hydroxyectoine conversely elevates it (Seip et al 2011 ). Recently, the field of application is expanding due to studies demonstrating anti-inflammatory effects of ectoine and ectoine derivatives in intestinal bowel disease and carbon nanoparticle induced airway inflammation, as well as protein stabilizing effects in neurodegenerative diseases (Abdel-Aziz et al 2013 , 2015 ; Bazazzadegan et al 2017 ; Unfried et al 2014 ). Promising applications as adjuvant treatment in these diseases led to a gain in CAGR (calculated annual growth rate) for the ectoine market and therefore to a demand for feasible biotechnological production processes (Becker and Wittmann 2020 ).…”

Biosynthesis of the Stress-Protectant and Chemical Chaperon Ectoine: Biochemistry of the Transaminase EctB

“…In a substantial subgroup of ectoine producers (Prabhu et al, 2004;Garcia-Estepa et al, 2006;Bursy et al, 2007;Czech et al, 2018a), ectoine is modified in a position-and stereo-specific reaction by the ectoine hydroxylase (EctD; EC 1.14.11.55) (Inbar et al, 1993;Bursy et al, 2007;Höppner et al, 2014). The resulting 5-hydroxyectoine often possesses superior functionpreserving attributes when compared with ectoine or it is preferentially produced during stationary phase (Borges et al, 2002;Manzanera et al, 2004;Schiraldi et al, 2006;Bursy et al, 2007;Harishchandra et al, 2010;Tanne et al, 2014;Abdel-Aziz et al, 2015).…”