ABSTRACT
Adequate nutrient supply is crucial for the proper development of the embryo. Although nutrient supply is determined by maternal diet, the gut microbiota also influences nutrient availability. While currently there is no cure for neural tube defects (NTDs), their prevention is largely amenable to maternal folic acid and inositol supplementation. The gut microbiota also contributes to the production of these nutrients, which are absorbed by the host, but its role in this context remains largely unexplored. In this study, we performed a functional and morphological analysis of the intestinal tract of loop-tail mice (Vangl2 mutants), a mouse model of folate/inositol-resistant NTDs. In addition, we investigated the changes in gut microbiota using 16S rRNA gene sequencing regarding (1) the host genotype; (2) the sample source for metagenomics analysis; (3) the pregnancy status in the gestational window of neural tube closure; (4) folic acid and (5) D-chiro-inositol supplementation. We observed that Vangl2+/Lp mice showed no apparent changes in gastrointestinal transit time or fecal output, yet exhibited increased intestinal length and cecal weight and gut dysbiosis. Moreover, our results showed that the mice supplemented with folic acid and D-chiro-inositol had significant changes in their microbiota composition, which are changes that could have implications for nutrient absorption.
Subject(s)
Microbiota , Neural Tube Defects , Female , Pregnancy , Mice , Animals , RNA, Ribosomal, 16S/genetics , Neural Tube Defects/prevention & control , Folic Acid/pharmacology , Dietary Supplements , Inositol , Disease Models, AnimalABSTRACT
As a new potentially mineralizable fluorinated surfactant, 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was synthesized and exposed to a standardized Zahn-Wellens test (OECD 302B). After the release of fluoride indicating the mineralization of the trifluoromethyl group, 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was subjected to a further biodegradation test carried out in a fixed bed bioreactor (FBBR). Evolution of biodegradation routes and pursuit was done by quadrupole linear ion trap mass spectrometer (QqLIT-MS) and quadrupole time-of-flight tandem mass spectrometer (QqTOF-MS). Biotransformation was initiated via hydroxylation in the alkyl chain at different positions. Hydroxy-9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate was further oxidized with subsequent scission of the molecule forming mainly p-(trifluoromethyl)phenolate, which was mineralized releasing inorganic fluoride. These results demonstrate, that the new synthesized fluorosurfactant 9-[4-(trifluoromethyl)phenoxy]nonane-1-sulfonate is completely biotransformed. However, some intermediates, depending on the position of hydroxylation, impede further mineralization.
Subject(s)
Biodegradation, Environmental , Sulfonic Acids/metabolism , Surface-Active Agents/metabolism , Bioreactors , Chromatography, High Pressure Liquid/methods , Sulfonic Acids/chemical synthesis , Tandem Mass SpectrometryABSTRACT
The synthesis of 1-(tert-butoxycarbonyl)-7-[1-(tert-butoxycarbonyl)-3-methylbutyl]-6-oxo-1,7-diazaspiro[4.5]decanes (S,S)-1a and (S,R)-1b is described. Derivatives 17a,b and 19a are prepared for use in peptide synthesis as constrained surrogates of the Pro-Leu and Gly-Leu dipeptides. The Ac-[Gly-Leu]-Met-NH(2) derivatives (S,S,S)-2a and (S,R,S)-2b, with the tripeptidic C-terminal region present in tachykinins, are also synthesized. Conformational analyses of these tripetide analogues by NMR experiments and molecular modeling calculations show that both (S,S,S)-2a and (S,R,S)-2b epimers are gamma-turn/distorted type II beta-turn mimetics.
