Influence of long-term antibiotic therapy on gut microbiome composition and metabolic profile in pulmonary tuberculosis

The use of long-term multicomponent antibiotic therapy is the most effective way to treat tuberculosis (TB). However, little is known about the effect of this chemotherapy on the human intestinal microflora. The purpose of this study was to analyze an effect of long-term antibiotic therapy on gut microbiome composition and metabolic profile in TB patients. We used deep sequencing of fecal samples from 23 treatment-naive TB patients to reconstruct the metabolic capacity and strain/species-level abundance in the gut microbiome. Two fecal samples were obtained from each patient: before and after treatment. We showed that TB treatment regimen does not disrupt the overall diversity of the gut microbiome but does have an impact on gut bacterial microbiome composition and metabolic profile. While taking first-line anti-tuberculosis drugs (isoniazid, rifampicin, ethambutol, pyrazinamide), TB patients showed an apparent increase in Actinobacteria abundance. Pairwise comparison of metagenomic data revealed 28 differentially represented bacterial taxa, of which three species Bacteroides cellulosilyticus, Enterocloster aldensis, Clostridium spiroforme were strongly enriched in TB patients post-chemotherapy, whereas 25 species were enriched in TB patients before treatment (Bifidobacterium catenulatum, Enterococcus faecium, Bacteroides salyersiae, Bacteroides xylanisolvens, Bacteroides eggerthii, Lachnospira eligens, Akkermansia muciniphila, Ruminococcus lactaris, etc.) (p 0.05). The metabolic profile of the gut microbiome was characterized by increased metabolic processes aimed at the growth and division of microbial cells. Iron is the main limiting factor for growth and reproduction. In addition, it is important to note the prevalence of glycolysis and lactate fermentation as the major means for energy production by intestinal microbiota

Short Route to the Total Synthesis of Natural Muricadienin and Investigation of Its Cytotoxic Properties

An original synthesis of the acetogenin muricadienin, the bioprecursor of solamin, has been developed. The key step in the five-step 41% overall yield synthesis is the catalytic cross-cyclomagnesiation reaction of functionally substituted 1,2-dienes with EtMgBr in the presence of Cp₂TiCl₂ and magnesium metal. It has been demonstrated for the first time that muricadienin exhibits a moderate in vitro inhibitory activity against topoisomerases I and IIα, key cell cycle enzymes. Using flow cytometry, muricadienin was shown to have high cytotoxicity toward the HEK293 kidney cancer cells (IC₅₀ 0.39 μM)