Vaginal microbiota: Potential targets for vulvovaginal candidiasis infection.

Vulvovaginal candidiasis (VVC) is the second most common cause of vaginal infection globally after bacterial vaginosis (BV) and associated with adverse reproductive and obstetric outcomes, including preterm delivery, sexually transmitted infections and pelvic inflammatory disease. Although effective control of VVC is achievable with the use of traditional treatment strategies (i.e., antifungals), the possibility of drug intolerance, treatment failure and recurrence, as well as the appearance of antifungal-resistant Candida species remain critical challenges. Therefore, alternative therapeutic strategies against VVC are urgently required. In recent years, an improved understanding of the dysbiotic vaginal microbiota (VMB) during VVC has prompted the consideration of administering -biotics to restore the balance of the VMB within the context of VVC prevention and treatment. Here, we aim to summarize the current evidence of the anti-Candida effects of probiotics, postbiotics and synbiotics and their potential use as an alternative/complementary therapy against VVC. Additionally, this review discusses advantages and challenges associated with the application of -biotics in VVC to provide guidance for their later use. We also review new developments in VVC therapy, i.e., vaginal microbiota transplantation (VMT) as an emerging live biotherapeutic therapy against VVC and discuss existing shortcomings associated with this nascent field, expecting to stimulate further investigations for introduction of new therapies against VVC.

Evaluation of the Anti-Aging Effects of a Probiotic Combination Isolated From Centenarians in a SAMP8 Mouse Model.

Population aging is a prominent global problem in today's society. However, there are currently no good methods to treat or prevent aging, so anti-aging research has crucial implications. In this research, we screened bacteria from centenarians, and finally selected four probiotics (Lactobacillus fermentum SX-0718, L. casei SX-1107, Bifidobacterium longum SX-1326, and B. animalis SX-0582) to form a probiotic combination. By using the senescence accelerated mouse prone 8 (SAMP8) model, the anti-aging effects of the probiotic combination were evaluated by using behavioural testing, neuroinflammation, intestinal inflammation, and intestinal microbiota. The results showed that probiotic combination improved the impaired spatial memory, motor dysfunction, and decreased exploratory behavior in aging mice. The probiotic combination inhibited Toll-like receptor 4 (TLR4)/nuclear factor kappa B (NFκB)-induced neuroinflammation and up-regulated the expression of Sirt 1 to protect hippocampal neurons. At the same time, the probiotic combination regulated the intestinal microbiota, reduced the relative abundance of Alistipes and Prevotella in SAMP8 mice, inhibited TLR4/NFκB-induced intestinal inflammation, and increased the expression of intestinal permeability related proteins zonula occludens-1 (ZO-1) and Occuldin. The anti-aging effects of the probiotic combination may be through the regulating intestinal microbiota and inhibiting TLR4/NFκB-induced inflammation. This research provides the basis and technical support for the future production and application of the probiotic combination.

Antidiabetic effect of an engineered bacterium Lactobacillus plantarum-pMG36e -GLP-1 in monkey model.

Glucagon-like peptide-1 (GLP-1) reduces postprandial hyperglycaemia, but its short half-life inhibits clinical application. The aim of the current study was to evaluate the treatment efforts of an engineered strain, Lactobacillus plantarum-pMG36e-GLP-1 (L. plantarum-pMG36e-GLP-1), that continuously expresses GLP-1 in spontaneous type 2 diabetes mellitus (T2DM) monkeys. After 7 weeks of oral supplementation with L. plantarum-pMG36e-GLP-1, the fasting blood glucose (FPG) of monkeys was significantly (p < 0.05) reduced to a normal level and only a small amount of weight was lost. The results of metagenomic sequencing showed that L. plantarum-pMG36e-GLP-1 caused a substantial (p < 0.05) reduction in the intestinal pathogen Prevotella and marked enhancement of butyrate-producing Alistipes genera. According to the functional analysis using Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathways, 19 metabolism-related pathways were significantly enriched in T2DM monkeys after treatment with L. plantarum-pMG36e-GLP-1. LC-MS faecal metabolomics analysis found 41 significant differential metabolites (11 higher and 30 lower) in monkeys after treatment pathways linked to the metabolism of cofactors and vitamins were the most relevant. The present study suggests that L. plantarum-pMG36e-GLP-1 had an impact on the gut microbial composition and faecal metabolomic profile in spontaneous T2DM monkeys and may be a novel candidate for diabetes treatment.

Combination of an engineered Lactococcus lactis expressing CXCL12 with light-emitting diode yellow light as a treatment for scalded skin in mice.

Impaired wound closure is an increasingly crucial clinical challenge. Recently, wound healing has shifted towards innovative treatments that exploit nanotechnology, biomaterials, biologics and phototherapy. Here, we constructed an engineered MG1363-pMG36e-mCXCL12 strain with pMG36e plasmid encoding stromal cell-derived factor 1α (named CXCL12) and evaluated the synergistic effects of light-emitting diode (LED) yellow light and MG1363-pMG36e-mCXCL12 on scald wounds in mice. The results indicated that the combined treatment with LED yellow light with mCXCL12 delivering strain accelerated wound closure, tissue remodelling, re-epithelialization and hair follicle regeneration and inhibited over-inflammation oppositely in the central and surrounding wounds by macroscopic, histopathologic and immunohistochemistry parameters. Furthermore, combination therapy increased the epidermal growth factor and Ki67-positive cells and upregulated beta-catenin (ß-catenin), cellular-myelocytomatosis (c-Myc), wingless-type MMTV integration site family member 1 (Wnt1), Jagged 1, neurogenic locus notch homolog protein 1 (Notch 1) and hairy and enhancer of split 1 (Hes 1) protein levels of the Wnt and Notch signalling pathways. It also facilitated collagen fibrogenesis and deposition and improved the activities of hydroxyproline, superoxide dismutase and glutathione peroxidase in scalded granulation tissue, in addition to reducing the inflammatory factors interleukin 1 beta (IL-1ß) and tumour necrosis factor alpha (TNF-α). The combined treatment effectively reduced skin pathogens Ralstonia and Acinetobacter to further reduce the risk of infection. Overall, combination of LED yellow light and MG1363-pMG36e-mCXCL12 represents a potential strategy for the treatment of cutaneous wounds.

Evaluation of Sodium Hypochlorite Irrigant, Bingpeng Irrigant, and Fufang Bingpeng Irrigant as Endodontic Irrigants During Passive Ultrasonic Irrigation.

Given the increasing prevalence of antibiotic resistance among bacterial strains and the side effects caused by synthetic drugs, it is increasingly important to investigate potential herbal alternatives. In the present study, antimicrobial, cell cytotoxicity, and cleaning tests were performed to evaluate the potential of Fufang Bingpeng irrigant as a root canal irrigant, in addition to q-PCR and high-throughput sequencing analyses. Our in vitro results showed a low minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of Fufang Bingpeng irrigant against Porphyromonas gingivalis ATCC 33277 (6.25 and 12.5%, respectively), Prevotella intermedius ATCC 25611 (6.25 and 6.25%, respectively), Fusobacterium nucleatum ATCC 25286 (6.25 and 6.25%, respectively), Enterococcus faecalis ATCC 19433 (25 and 25%, respectively), and Bacteriodes fragilis ATCC 25285 (12.5 and 12.5%, respectively). Furthermore, it effectively removed the remaining debris and increased the number of open dentinal tubules in root canals compared to the NaCl irrigant (p < 0.05). Fufang Bingpeng irrigant also presented low cytotoxicity to L929 cells compared to the NaClO irrigant. The in vivo results indicated that all irrigants used significantly reduced the number of bacteria compared to the number prior to treatment, and only 1/104.95 bacteria remained in the root canal following the use of Fufang Bingpeng irrigant (p < 0.001). Moreover, the high-throughput sequencing results indicated that all irrigants markedly enhanced the α diversity in the root canal compared to the before preparation control group, while Fufang Bingpeng maintained better microbial diversity than other groups. Therefore, Fufang Bingpeng irrigant presents a promising alternative for use as a root canal irrigant in clinical settings.

Evaluation of the Treatment Effect of Aloe vera Fermentation in Burn Injury Healing Using a Rat Model.

Burn injury is a growing medical problem associated with public health, and few effective agents are available for treatment of this disease. In the present study, a burn injury rat model was developed and the accelerated effect of Aloe vera fermentation on burn injury healing was evaluated. Our results indicated that Aloe vera fermentation could markedly reduce the DPPH (56.12%), O2·- (93.5%), ·OH (76.12%), Fe2+ chelation (82%), and oxygen-reduction activity (0.28 µg/ml) and significantly inhibited the growth of pathogens S. typhimurium ATCC 13311 (inhibition zone diameter: 14 mm), S. enteritidis ATCC13076 (IZD: 13 mm), S. flexneri ATCC 12022 (IZD: 18 mm), E. coli 44102 (IZD: 10 mm), L. monocytogenes ATCC 19111 (IZD: 18 mm), S. dysenteriae 301 (IZD: 20 mm), S. aureus COWAN1 (IZD: 19 mm), and P. acnes ATCC 11827 (IZD: 25 mm) in vitro. The in vivo results indicated that Aloe vera fermentation produced more eosinophils and fibroblasts and less vessel proliferation compared with the model group on the 14th day, which had greatly accelerated burn injury healing via shedding of the scab and promoting hair growth. ELISA results indicated that Aloe vera fermentation had significantly reduced the production of proinflammatory factors TNF-α and IL-1ß (p < 0.05) and greatly enhanced the yield of anti-inflammatory factor IL-4 in animal serum (p < 0.05). In addition, the high-throughput sequencing results indicated that Aloe vera fermentation obviously increased the percentage of Firmicutes (65.86% vs. 49.76%), while reducing the number of Bacteroidetes (27.60% vs. 45.15%) compared with the M group at the phylum level. At the genus level, Aloe vera fermentation increased the probiotic bacteria Lactobacillus (3.13% vs. 2.09%) and reduced the pathogens Prevotella (10.60% vs.18.24%) and Blautia (2.91% vs. 16.41%) compared with the M group. Therefore, we concluded that the use of Aloe vera fermentation significantly accelerates burn injury healing via reduction of the severity of inflammation and through modification of gut microbiota.

Reclamation of Chinese herb residues using probiotics and evaluation of their beneficial effect on pathogen infection.

Environmental pollution caused by herb residues and the huge waste of medicinal ingredients contained in herb residues hinder the development of traditional Chinese medicine enterprises. To solve this problem, several probiotics were tested, and Lactobacillus plantarum (HM218749) was finally selected for the reuse of herb residues of Jianweixiaoshi tablets. A mouse model of Helicobacter pylori infection was developed to evaluate the anti-H. pylori infection activity of the herb residue fermentation supernatant using a urease activity test, histological imaging, an enzyme-linked immunosorbent assay (ELISA) and denaturing gel gradient electrophoresis (DGGE). The results demonstrated that the herb residue fermentation supernatant successfully inhibited urease activity, slowed cell infiltration in the gastric area and significantly reduced the production of interleukin-6 (IL-6), IL-8 and TNF-α in the treatment group (p<0.01). In addition, the DGGE results indicated that the herb residue fermentation supernatant was beneficial for the recovery of the disturbed microbiota in the infected model to the normal condition, in which L. gasseri (GU417842.1) and L. johnsonii (HQ828141.1) were dominant in all groups. Therefore, the probiotics exhibited strong potential for the development of herb residues in this study, and the products showed strong potential in curing H. pylori infections.

Reclamation of Herb Residues Using Probiotics and Their Therapeutic Effect on Diarrhea.

Residues from herbal medicine processing in pharmaceutical plants create a large amount of waste (herb residues), which consists mainly of environmental pollution and medicinal waste. In order to resolve this problem, probiotics of Bacillus (B.) subtilis, Aspergillus (A.) oryzae, and Lactobacillus (L.) plantarum M3 are selected to reuse herb residue of Jianweixiaoshi tablets (JT), and an antibiotic-associated diarrhea (AAD) mouse model was established to evaluate the therapeutic effects of the herb residue fermentation supernatant. Our results indicated that the fermentation supernatant had scavenged 77.8% of 2,2-diphenyl-1-picrylhydrazyl (DPPH), 78% of O2•-, 36.7% of •OH, 39% of Fe2+ chelation, and 716 mg/L reducing power. The inhibition zones for Salmonella (S.) typhimurium, S. enteritidis, Shigella (Sh.) flexneri, Escherichia (E.) coli, Listeria (L.) monocytogenes, Sh. dysenteriae 301, and Staphylococcus (S.) aureus were 17, 14, 19, 18, 20, 19, and 20 mm, respectively. The in vivo results indicated that the fermentation supernatant resulted in a high diarrhea inhibition rate (56%, p < 0.05), greatly enhanced the disruption of bacterial diversity caused by antibiotics, and restored the dominant position of L. johnsonii in the treatment and recovery stages. Therefore, the combination of the herb residue and probiotics suggests a potential to explore conversion of these materials for the possible development of therapies for AAD.