The Effects of Iron Deficiency on the Gut Microbiota in Women of Childbearing Age.

Iron deficiency anemia (IDA) is the most prevalent and common nutritional deficiency worldwide and is a global health problem with significant risk, particularly among women of reproductive age. Oral iron supplementation is the most widely used and cost-effective treatment for iron deficiency and IDA. However, there are limitations regarding side effects such as enteritis, treatment compliance, and bioavailability. Intestinal microbiome characteristic research has been recently conducted to overcome these issues, but more is needed. Against this background, a metagenomics study on the 16S gene in the feces of young women vulnerable to IDA was conducted. As a result of analyzing 16 normal subjects and 15 IDA patients, significant differences in bacterial community distribution were identified. In particular, a significant decrease in Faecalibacterium was characteristic in IDA patients compared with normal subjects. Furthermore, in the case of patients who recovered from IDA following iron supplementation treatment, it was confirmed that Faecalibacterium significantly recovered to normal levels. However, no significance in beta diversity was seen compared with before treatment. There were also no differences in the beta diversity results between the recovered and normal subjects. Therefore, intestinal dysbiosis during the disease state was considered to be restored as IDA improved. Although the results were derived from a limited number of subjects and additional research is needed, the results of this study are expected to be the basis for developing treatment and prevention strategies based on host-microbiome crosstalk in IDA.

A Clinical Trial to Evaluate the Efficacy of α-Viniferin in Staphylococcus aureus - Specific Decolonization without Depleting the Normal Microbiota of Nares.

Staphylococcus aureus is currently a significant multidrug-resistant bacterium, causing severe healthcare-associated and community-acquired infections worldwide. The current antibiotic regimen against this pathogen is becoming ineffective due to resistance, in addition, they disrupt the normal microbiota. It highlights the urgent need for a pathogen-specific drug with high antibacterial efficacy against S. aureus. α-Viniferin, a bioactive phytochemical compound, has been reported to have excellent anti-Staphylococcus efficacy as a topical agent. However, so far, there were no clinical trials that have been conducted to elucidate its efficacy. The present study aimed to investigate the antibacterial efficacy of α-viniferin against S. aureus in a ten-day clinical trial. Based on the results, α-viniferin showed 50% minimum inhibitory concentrations (MIC50 values) of 7.8 µg/ml in culture broth medium. α-Viniferin was administered in the nares three times a day for ten days using a sterile cotton swab stick. Nasal swab specimens were collected before (0 days) and after finishing the trial (10th day), and then analyzed. In the culture and RT-PCR-based analysis, S. ureus was reduced significantly: 0.01. In addition, 16S ribosomal RNA-based amplicon sequencing analysis showed that S. aureus reduced from 51.03% to 23.99% at the genus level. RNA-seq analysis was also done to gain insights into molecular mechanisms of α-viniferin against S. aureus, which revealed that some gene groups were reduced in 5-fold FC cutoff at two times MIC conditions. The study results demonstrate α-viniferin as a potential S. aureus-specific drug candidate.

In vitro activity of DNF-3 against drug-resistant Mycobacterium tuberculosis.

Due to the emergence of multidrug-resistant and extensively drug-resistant (XDR) strains of Mycobacterium tuberculosis, new antituberculosis drugs are urgently required to improve the efficacy of current tuberculosis (TB) treatment. To achieve this goal, ca. 1000 chemical compounds were screened for potential antimycobacterial activity, among which methyl 5-(2-diethylaminoethoxy)-7,12-dioxo-7,12 dihydrodinaphtho[1,2-b;2',3'-d]furan-6-carboxylate (DNF-3) showed strong activity against all of the tested drug-susceptible and -resistant M. tuberculosis strains, with 50% minimum inhibitory concentrations (MIC50 values) of 0.02-0.39 µg/mL both in culture broth and within murine RAW 264.7 macrophage cells. When DNF-3 was used in combination with rifampicin or streptomycin, it exhibited direct synergy against XDR-TB and an additive effect against M. tuberculosis H37Rv. DNF-3 displayed a long post-antibiotic effect (PAE) that was comparable with rifampicin but was superior to isoniazid, streptomycin and ethambutol. Importantly, DNF-3 showed no cytotoxicity to any cell line tested, with a selectivity index (SI) of >32. DNF-3 was also active against 27 nontuberculous mycobacteria (NTM) strains, Staphylococcus spp. and Streptococcus spp. Taken together, these results indicate that DNF-3 is a promising new candidate drug for treating TB. Further studies are warranted to establish the in vivo effect and therapeutic potential of DNF-3.

In vitro activity of collinin isolated from the leaves of Zanthoxylum schinifolium against multidrug- and extensively drug-resistant Mycobacterium tuberculosis.

BACKGROUND: Tuberculosis is a very serious infectious disease that threatens humanity, and the emergence of multidrug-resistant (MDR), extensively drug-resistant (XDR) strains resistant to drugs suggests that new drug development is urgent. In order to develop new tuberculosis drug, we have conducted in vitro anti-tubercular tests on thousands of plant-derived substances and finally found collinin extracted from the leaves of Zanthoxylum schinifolium, which has an excellent anti-tuberculosis effect. PURPOSE: To isolate an anti-tubercular bioactive compound from the leaves of Z. schinifolium and evaluate whether this agent demonstrates any potential in vitro characteristics suitable for the development of future anti-tubercular drugs to treat MDR and XDR Mycobacterium tuberculosis. METHODS: The methanolic extracts of the leaves of Z. schinifolium were subjected to bioassay-guided fractionation against M. tuberculosis using a microbial cell viability assay. In addition, following cell cytotoxicity assay, an intracellular anti-mycobacterial activity of the most active anti-tubercular compound was investigated after it was purified. RESULTS: The active compound with anti-tubercular activity isolated from leaves of Z. schinifolium was identified as a collinin. The extracted collinin showed anti-tubercular activity against both drug-susceptible and -resistant strains of M. tuberculosis at 50% minimum inhibitory concentrations (MIC50s) of 3.13-6.25 µg/ml in culture broth and MIC50s of 6.25-12.50 µg/ml inside Raw264.7 and A549 cells. Collinin had no cytotoxicity against human lung pneumocytes up to a concentration of 100 µg/ml (selectivity index > 16-32). CONCLUSIONS: Collinin extracted from the leaves of Z. schinifolium significantly inhibits the growth of MDR and XDR M. tuberculosis in the culture broth. In addition, it also inhibits the growth of intracellular drug-susceptible and drug-resistant tuberculosis in Raw264.7 and A549 cells. To our knowledge, this is the first report on the in vitro anti-tubercular activity of collinin, and our data suggest collinin as a potential drug to treat drug-resistant tuberculosis. Further studies are warranted to assess the in vivo efficacy and therapeutic potential of collinin.

In vitro Antitubercular Activity of 3-Deoxysappanchalcone Isolated From the Heartwood of Caesalpinia sappan Linn.

Responsible for nearly 1.5 million deaths every year, the infectious disease tuberculosis remains one of the most serious challenges to global health. The emergence of multidrug-resistant tuberculosis and, more recently, extensively drug-resistant tuberculosis poses a significant threat in our effort to control this epidemic. New drugs are urgently needed to combat the growing threat of antimicrobial resistance. To achieve this goal, we screened approximately 500 species of medicinal plant methanol extracts and their solvent partitioned fractions for potential inhibitors of Mycobacterium tuberculosis growth. Using microdilution screening, the ethyl acetate solvent partitioned fraction from the heartwood of Caesalpinia sappan exhibited strong antitubercular activity. We isolated the active compound and identified it as 3-deoxysappanchalcone. The extracted 3-deoxysappanchalcone possessed activity against both drug-susceptible and drug-resistant strains of M. tuberculosis at MIC50 s of 3.125-12.5 µg/mL in culture broth and MIC50 s of 6.25-12.5 µg/mL inside macrophages and pneumocytes. 3-Deoxysappanchalcone was also found to act in partial synergy with streptomycin/ethambutol against M. tuberculosis H37Rv. 3-Deoxysappanchalcone had no cytotoxicity against the A549 cell line up to a concentration of 100 µg/mL (selectivity index > 8-32). Further studies are warranted to establish the in vivo effect and therapeutic potential of 3-deoxysappanchalcone. Copyright © 2017 John Wiley & Sons, Ltd.

Thymoquinone (TQ) inhibits the replication of intracellular Mycobacterium tuberculosis in macrophages and modulates nitric oxide production.

BACKGROUND: Human tuberculosis, which is caused by the pathogen Mycobacterium tuberculosis, remains a major public health concern. Increasing drug resistance poses a threat of disease resurgence and continues to cause considerable mortality worldwide, which necessitates the development of new drugs with improved efficacy. Thymoquinone (TQ), an essential compound of Nigella sativa, was previously reported as an active anti-tuberculosis agent. METHODS: In this study, the effects of TQ on intracellular mycobacterial replication are examined in macrophages. In addition, its effect on mycobacteria-induced NO production and pro-inflammatory responses were investigated in Mycobacterium tuberculosis (MTB)-infected Type II human alveolar and human myeloid cell lines. RESULTS: TQ at concentrations ranging from 12.5 to 25 µg/mL and 6.25 to 12.5 µg/mL reduced intracellular M. tuberculosis H37Rv and extensively drug-resistant tuberculosis (XDR-TB) 72 h post-infection in RAW 264.7 cells. TQ treatment also produced a concentration-dependent reduction in nitric oxide production in both H37Rv and XDR-TB infected RAW 264.7 cells. Furthermore, TQ reduced the expression of inducible nitric oxide synthase (iNOS) and pro-inflammatory molecules such as tumor necrosis factor-alpha (TNF-α) and interlukin-6 (IL-6) in H37Rv-infected cells and eventually reduced pathogen-derived stress in host cells. CONCLUSIONS: TQ inhibits intracellular H37Rv and XDR-TB replication and MTB-induced production of NO and pro-inflammatory molecules. Therefore, along with its anti-inflammatory effects, TQ represents a prospective treatment option to combat Mycobacterium tuberculosis infection.