UNASSIGNED: Psilocybin and related tryptamines have come into the spotlight in recent years as potential therapeutics for depression. Research on the mechanisms of these effects has historically focused on the direct effects of these drugs on neural processes. However, in addition to such neural effects, alterations in peripheral physiology may also contribute to their therapeutic effects. In particular, substantial support exists for a gut microbiome-mediated pathway for the antidepressant efficacy of other drug classes, but no prior studies have determined the effects of tryptamines on microbiota.
UNASSIGNED: To address this gap, in this preliminary study, male Long Evans rats were treated with varying dosages of oral psilocybin (0.2 or 2 mg/kg), norbaeocystin (0.25 or 2.52 mg/kg), or vehicle and their fecal samples were collected 1 week and 3 weeks after exposure for microbiome analysis using integrated 16S ribosomal DNA sequencing to determine gut microbiome composition.
UNASSIGNED: We found that although treatment with neither psilocybin nor norbaeocystin significantly affected overall microbiome diversity, it did cause significant dose- and time-dependent changes in bacterial abundance at the phylum level, including increases in Verrucomicrobia and Actinobacteria, and decreases in Proteobacteria.
UNASSIGNED: These preliminary findings support the idea that psilocybin and other tryptamines may act on the gut microbiome in a dose- and time-dependent manner, potentially identifying a novel peripheral mechanism for their antidepressant activity. The results from this preliminary study also suggest that norbaeocystin may warrant further investigation as a potential antidepressant, given the similarity of its effects to psilocybin.

UNASSIGNED: The oral cavity and gut tract, being interconnected and rich in microbiota, may have a shared influence on gingivitis. However, the specific role of distinct gut microbiota taxa in gingivitis remains unexplored. Utilizing Mendelian Randomization (MR) as an ideal method for causal inference avoiding reverse causality and potential confounding factors, we conducted a comprehensive two-sample MR study to uncover the potential genetic causal impact of gut microbiota on gingivitis.
UNASSIGNED: Instrumental variables were chosen from single nucleotide polymorphisms (SNPs) strongly associated with 418 gut microbiota taxa, involving 14,306 individuals. Gingivitis, with 4,120 cases and 195,395 controls, served as the outcome. Causal effects were assessed using random-effect inverse variance-weighted, weighted median, and MR-Egger methods. For replication and meta-analysis, gingivitis data from IEU OpenGWAS were employed. Sensitivity analyses included Cochran\'s Q tests, funnel plots, leave-one-out analyses, and MR-Egger intercept tests. This study aimed to assess the genetic correlation between the genetically predicted gut microbiota and gingivitis using linkage disequilibrium score regression (LDSC).
UNASSIGNED: Three gut microbiota taxa (class Actinobacteria id.419, family Defluviitaleaceae id.1924, genus Defluviitaleaceae UCG011 id.11287) are predicted to causally contribute to an increased risk of gingivitis (P< 0.05). Additionally, four gut microbiota taxa (class Actinobacteria id.419, genus Escherichia Shigella id.3504, genus Ruminococcaceae UCG002 id.11360) potentially exhibit inhibitory causal effects on the risk of gingivitis (P< 0.05). No significant evidence of heterogeneity or pleiotropy is detected. Our findings indicate a suggestive genetic correlation between class Actinobacteria id.419, class Bacteroidia id.912, family Defluviitaleaceae id.1924, genus Escherichia Shigella id.3504 and gingivitis.
UNASSIGNED: Our study establishes the genetic causal effect of 418 gut microbiota taxa on gingivitis, offering insights for clinical interventions targeting gingivitis. Subsequent research endeavors are essential to corroborate the findings of our present study.

Chronic periodontitis caused by the bacteria Porphyromonas gingivalis is thought to be a risk factor for the advancement of oral squamous cell carcinoma (OSCC). Virulence factors of P. gingivalis include gingipains, outer membrane surface lipoproteins, and fimbriae contribute to the activation of oncogenic pathways in OSCC by up-regulating different cytokines. Gingipains (Arg and Lys) proteases have an important role in the activation of proMMP-9, which promotes cellular invasion and metastatic ability of OSCC. Thus gingipains and MMP-9 were actively investigated as potential therapeutic targets in OSCC therapy. Various natural bioactive compounds from Actinobacteria have been explored for their anticancer potential in a variety of cancers, but very few studies have been reported in OSCC. Therefore, the current study is focused to identify potential actinobacterial compounds that can be considered as a therapeutic target against gingipains and inflammatory proteins in OSCC through high-throughput virtual screening, Molecular Docking (MD), and Molecular Dynamics Simulation (MDS) approaches. A total of 179 bioactive secondary metabolites of Actinobacteria were explored for their binding affinity against six virulence proteins of P. gingivalis. The Molecular Docking studies revealed that among 179 metabolites screened, Actinosporin G showed a highly acceptable binding affinity of -7.9 kcal/mol with RgpB (1CVR), and exhibited multi-protein targeting and drug-likeness property and passed level of toxicity. Comprehensive docking interaction of the best top-ranked Actinosporin G with OSCC-related protein targets illustrated high binding affinity towards MMP-9 and JAK-1 proteins among all targeted receptor proteins. The molecular dynamic (MD) simulation has been executed for the metabolite Actinosporin G for both bacterial gingipain (RgpB) and MMP-9 & JAK-1 showed stable intermolecular binding with both hydrogen and hydrophobic interactions. In conclusion, this work suggests that the bioactive secondary metabolite of Actinosporin G from Actinobacteria genera may serve as a promising therapy for P. gingivalis-induced OSCC.
UNASSIGNED:
UNASSIGNED: The online version contains supplementary material available at 10.1007/s40203-024-00209-0.

Obesity is a metabolic and chronic inflammatory disease involving genetic and environmental factors. This study aimed to investigate the causal relationship among gut microbiota abundance, plasma metabolomics, peripheral cell (blood and immune cell) counts, inflammatory cytokines, and obesity.
Summary statistics of 191 gut microbiota traits (N = 18,340), 1,400 plasma metabolite traits (N = 8,299), 128 peripheral cell counts (blood cells, N = 408,112; immune cells, N = 3,757), 41 inflammatory cytokine traits (N = 8,293), and 6 obesity traits were obtained from publicly available genome-wide association studies. Two-sample Mendelian randomization (MR) analysis was applied to infer the causal links using inverse variance-weighted, maximum likelihood, MR-Egger, weighted median, weighted mode, and Wald ratio methods. Several sensitivity analyses were also utilized to ensure reliable MR results. Finally, we used mediation analysis to identify the pathway from gut microbiota to obesity mediated by plasma metabolites, peripheral cells, and inflammatory cytokines.
MR revealed a causal effect of 44 gut microbiota taxa, 281 plasma metabolites, 27 peripheral cells, and 8 inflammatory cytokines on obesity. Among them, five shared causal gut microbiota taxa belonged to the phylum Actinobacteria, order Bifidobacteriales, family Bifidobacteriaceae, genus Lachnospiraceae UCG008, and species Eubacterium nodatum group. Furthermore, we screened 42 shared causal metabolites, 7 shared causal peripheral cells, and 1 shared causal inflammatory cytokine. Based on known causal metabolites, we observed that the metabolic pathways of D-arginine, D-ornithine, linoleic acid, and glycerophospholipid metabolism were closely related to obesity. Finally, mediation analysis revealed 20 mediation relationships, including the causal pathway from gut microbiota to obesity, mediated by 17 metabolites, 2 peripheral cells, and 1 inflammatory cytokine. Sensitivity analysis represented no heterogeneity or pleiotropy in this study.
Our findings support a causal relationship among gut microbiota, plasma metabolites, peripheral cells, inflammatory cytokines, and obesity. These biomarkers provide new insights into the mechanisms underlying obesity and contribute to its prevention, diagnosis, and treatment.

Gut microbiota (GM) is a crucial underlying player during sepsis pathogenesis. However, the causal relationship is unclear and remains to be determined. A two-sample Mendelian randomization study was implemented. The statistical data about sepsis together with GM summarized from genome-wide association studies were evaluated. Instrumental variables were defined as single-nucleotide polymorphisms with prominent correlations with exposure. The inverse-variance-weighted test was employed as a major approach of Mendelian randomization analysis to estimate of causal relationships. The inverse-variance-weighted analysis results demonstrated that at different taxa levels, Actinobacteria and Bifidobacteriaceae influence sepsis. Actinobacteria had negative relationships to sepsis risk at the phylum (β = -0.34, SE = 0.10, p = 0.0008) and class (β = -0.23, SE = 0.07, p = 0.0011) levels in outcome coded ieu-b-69. Actinobacteria at the phylum level (β = -0.22, SE = 0.10, p = 0.027) was also negatively associated with sepsis in outcome coded ieu-b-4980. Bifidobacteriaceae at the order (β = -0.20, SE = 0.06, p = 0.0021), family (β = -0.20, SE = 0.06, p = 0.0021), and genus (β = -0.20, SE = 0.06, p = 0.0007) levels were all negatively correlated with the risk of sepsis in outcome coded ieu-b-69. The results of the Wald ratio model showed that Tyzzerella genus (OR (95%CI) = 0.6902[0.4907,0.9708], p = 0.0331) and Gastranaerophilales order (OR (95%CI) = 0.5907[0.3516,0.9926], p = 0.0468) were negatively connected with sepsis. This study implied at different taxa levels Actinobacteria and Bifidobacteriaceae, Tyzzerella genus, and Gastranaerophilales order have a causal relationship with sepsis, indicating that they are protective factors for the incidence of sepsis.

In this study, an actinomycete was isolated from sea mud. The strain K1 was identified as Saccharomonospora sp. by 16S rDNA. The optimal enzyme production temperature, initial pH, time, and concentration of the inducer of this actinomycete strain K1 were 37 °C, pH 8.5, 72 h, and 2% dextran T20 of medium, respectively. Dextranase from strain K1 exhibited maximum activity at 8.5 pH and 50 °C. The molecular weight of the enzyme was <10 kDa. The metal ions Sr2+ and K+ enhanced its activity, whereas Fe3+ and Co2+ had an opposite effect. In addition, high-performance liquid chromatography showed that dextran was mainly hydrolyzed to isomaltoheptose and isomaltopentaose. Also, it could effectively remove biofilms of Streptococcus mutans. Furthermore, it could be used to prepare porous sweet potato starch. This is the first time a dextranase-producing actinomycete strain was screened from marine samples.

UNASSIGNED: Studies have found that gut microbiota may be associated with the development of erectile dysfunction (ED); however, the exact link between the two remains unclear. This study aimed to elucidate the relationship between the gut microbiota and the risk of ED from a genetic perspective.
UNASSIGNED: We investigated the relationship between the gut microflora and ED using two-sample Mendelian randomization. GWAS-pooled data for ED were obtained from 223805 participants in Europe. GWAS summary data for ED were obtained from 223805 subjects in Europe and that for the gut microbiota were obtained from 18340 participants in 24 cohorts. We used the inverse-variance weighted (IVW) estimator as the primary method for the preliminary analysis, and the MR-Egger, weighted median (WM), simple model, and weighted model as secondary methods. We used Cochrane\'s Q-test, to detect heterogeneity, MREgger to detect pleiotropy, and the leave-one-out method to test the stability of the MR results. Ultimately, we genetically predicted a causal relationship between 211 gut microbiota and ED.
UNASSIGNED: A total of 2818 SNPs associated with gut microflora were screened in the ED correlation analysis based on the assumption of instrumental variables. The results of MR analysis showed a causal relationship between the six gut microbes and ED occurrence. The results of the fixed effects IVW method revealed five gut microflora, including Lachnospiraceae (OR, 1.265; P = 0.008), Lachnospiraceae NC2004 group (OR, 1.188; P = 0.019), Oscillibacter (OR, 1.200; P = 0.015), Senegalimassilia (OR, 1.355; P = 0.002), Tyzzerella3 (OR, 1.133; P = 0.022), to be negatively associated with ED. In addition, the IVW method revealed Ruminococcaceae UCG-013 (OR, 0.827; P = 0.049) to be positively associated with ED. Quality control results showed no heterogeneity or horizontal pleiotropy in the MR analysis (P > 0.05).
UNASSIGNED: Six gut microbes were genetically associated with ED; of which, Ruminococcaceae UCG-013 was causally associated with a reduced risk of ED development. Our findings provide a new direction for research on the prevention and treatment of ED; however, the mechanisms and details require further investigation.

The genus Nocardia comprises gram-positive bacteria, most of which are pathogenic and cause opportunistic infections of the lungs, skin, and brain in humans. Based on a collaboration study with the Medical Mycology Research Center, Chiba University, we focused on Nocardia actinomycetes as a new natural-product resource. First, by culturing (monoculture) Nocardia in various media, we isolated a new aminocyclitol nabscessin A from Nocardia abscessus IFM10029T and a new γ-lactone inohanalactone from Nocardia inohanaensis IFM0092T. On the other hand, by imitating the state in which the genus Nocardia actinomycete infects animal cells and culturing the genus in the presence of animal cells (coculture), this genus was expected to produce new compounds through interactions with the animal cells. Using mouse macrophage-like cells (J774.1) as animal cells, a new pantothenic acid amide derivative and a cyclic peptide, nocarjamide, with Wnt signal activation activity were isolated from Nocardia tenerifensis IFM10554T strain.

The increases in titanium dioxide nanoparticles (TiO2-NPs) released into the environment have raised concerns about their toxicity. However, their phytotoxic impact on plants is not well studied. Therefore, this study aimed at a deeper understanding of the TiO2-NPs phytotoxic impact on barley (Hordeum vulgare) growth and stress defense. We also hypothesized that soil inoculation with bioactive Rhodospirillum sp. JY3 strain can be applied as a biological fertilizer to alleviate TiO2-NPs phytotoxicity. At TiO2-NPs phytotoxicity level, photosynthesis was significantly retarded (∼50% reduction) in TiO2-NPs treated-barley plants which accordingly affect the biomass of barley plants. This retardation was accompanied by a remarkable induction of oxidative damage (H2O2, lipid peroxidation) with a concomitant reduction in the antioxidant defense metabolism. At a glance, Rhodospirillum sp. JY3 ameliorated the reduction in growth by enhancing the photosynthetic efficiency in contaminated barley plants. Moreover, Rhodospirillum sp. JY3 inoculation reduced the oxidative damage induced by TiO2-NPs via quenching H2O2 production and lipid peroxidation. Regarding the antioxidant defense arsenal, Rhodospirillum sp. JY3 enhanced both enzymatic (e.g. peroxidase (POX), catalase (CAT), superoxide dismutase (SOD), …. etc.) and non-enzymatic (glutathione (GSH), ascorbate (ASC), polyphenols, flavonoids, tocopherols) antioxidants in shoots and to a greater extent roots of barley plants. Moreover, the inoculation significantly enhanced the heavy metal-detoxifying metabolites (eg. phytochelatins, glutaredoxin, thioredoxin, peroxiredoxin) as well as metal-detoxifying enzymes in barley shoots and more apparently in roots of TiO2-NPs stressed plants. Furthermore, there was an organ-specific response to TiO2-NPs and Rhodospirillum sp. JY3. To this end, this study shed light, for the first time, on the molecular bases underlie TiO2-NPs stress mitigating impact of Rhodospirillum sp. JY3 and it introduced Rhodospirillum sp. JY3 as a promising eco-friendly tool in managing environmental risks to maintain agricultural sustainability.

Synbiotics are increasingly used by the general population to boost immunity. However, there is limited evidence concerning the immunomodulatory effects of synbiotics in healthy individuals. Therefore, we conducted a double-blind, randomized, placebo-controlled study in 106 healthy adults. Participants were randomly assigned to receive either synbiotics (containing Bifidobacterium lactis HN019 1.5 × 108 CFU/d, Lactobacillus rhamnosus HN001 7.5 × 107 CFU/d, and fructooligosaccharide 500 mg/d) or placebo for 8 weeks. Immune parameters and gut microbiota composition were measured at baseline, mid, and end of the study. Compared to the placebo group, participants receiving synbiotic supplementation exhibited greater reductions in plasma C-reactive protein (P = 0.088) and interferon-gamma (P = 0.008), along with larger increases in plasma interleukin (IL)-10 (P = 0.008) and stool secretory IgA (sIgA) (P = 0.014). Additionally, synbiotic supplementation led to an enrichment of beneficial bacteria (Clostridium_sensu_stricto_1, Lactobacillus, Bifidobacterium, and Collinsella) and several functional pathways related to amino acids and short-chain fatty acids biosynthesis, whereas reduced potential pro-inflammatory Parabacteroides compared to baseline. Importantly, alternations in anti-inflammatory markers (IL-10 and sIgA) were significantly correlated with microbial variations triggered by synbiotic supplementation. Stratification of participants into two enterotypes based on pre-treatment Prevotella-to-Bacteroides (P/B) ratio revealed a more favorable effect of synbiotic supplements in individuals with a higher P/B ratio. In conclusion, this study suggested the beneficial effects of synbiotic supplementation on immune parameters, which were correlated with synbiotics-induced microbial changes and modified by microbial enterotypes. These findings provided direct evidence supporting the personalized supplementation of synbiotics for immunomodulation.