Biology subjects

Spacova, I.

Publications and source records attributed to Spacova, I..

7 recordsLinked to original sources

bioRxiv2026

Exopolysaccharides of Lactobacillus crispatus mediate key balancing interactions with the vaginal mucosa

Lactobacillus crispatus is a dominant member of the healthy vaginal microbiota, yet the mechanisms by which it modulates host immunity remain poorly defined, in part due to the lack of tractable in vivo models. Here, we integrate bacterial genetics, in vitro epithelial systems, human-derived data and proteomic approach (Olink) to uncover a critical role for L. crispatus exopolysaccharides (EPS) in shaping the bacteria-vagina interactions. Comparative genomics identified a conserved EPS biosynthetic locus, with the priming glycosyltransferase gene epsE emerging as a regulatory node, in line with its distinct expression in human vaginal samples. Functional disruption of epsE abrogated L. crispatus EPS production and revealed its role for immune modulation. In human vaginal epithelial monolayers, EPS presence enhanced immune-regulatory (LAP TGF-beta-1) and anti-inflammatory (CST5) responses, whereas its absence triggered elevated pro-inflammatory cytokines (IL-1{beta}, IL-6, IL-8) and matrix metalloproteinase (MMP-10). In a 3D vaginal organotypic model, EPS increased chemokines (CXCL5, CXCL6) linked to immune surveillance and the presence of the markers was validated in vaginal samples of healthy volunteers. These findings position EPS as a key immunomodulatory structure of L. crispatus, advancing our mechanistic understanding of host-commensal interactions and informing microbiome-based strategies to promote vaginal health.

microbiology↗

bioRxiv2025

Vitamin B2 Production by Vaginal Lactobacilli Promotes Symbiosis

The human vaginal microbiome, particularly with lactobacilli as the main inhabitants, plays a key role in maintaining womens health. While lactic acid-mediated pathogen exclusion is well known, broader metabolic functions of vaginal lactobacilli remain underexplored. In this study, we analyzed the vaginal microbiome and metabolome of 258 healthy women from the Isala program. Using targeted metabolomics analysis, we detected a high prevalence with strong interpersonal differences of most B-vitamins, their precursors, and vitamin A in the vaginal microenvironment. Riboflavin (B2) and biotin (B7) showed strong associations with Lactobacillus crispatus and Limosilactobacillus sp. Comparative genomics, phenotypic assays, and in vivo metatranscriptomic data (VIRGO2) collectively confirmed riboflavin biosynthesis by these taxa. Using a riboflavin overproducing Lim. reuteri as a functional model, we showed that microbially derived riboflavin and its pathway intermediates are transported across the vaginal epithelium and modulate host redox balance, cytokine production, and activation of mucosal-associated invariant T (MAIT) cells via induction of MR1 (Major histocompatibility complex, class I-related protein receptor), revealing a potential immunometabolic interface between the vaginal microbiota and its host.

microbiology↗

bioRxiv2025

The female intimate microbiome space

Despite its importance in health, the female skin microbiome remains understudied. In this study we explored microbial dispersal across intimate body sites, including the vagina, groins, breast and mouth. Microbial similarity correlated with physical proximity, suggesting dispersal influenced by hygiene or sexual activity. Notably, lactobacilli were unexpectedly abundant on breast skin. These findings highlight the need for research into microbiome dynamics and their implications for womens health.

microbiology↗

bioRxiv2024

Lacticaseibacillus rhamnosus GG in a chewable colonizes the nose and facilitates local immune benefits in allergic rhinoconjunctivitis patients

Current treatments fall short in managing allergic rhinitis (AR), emphasizing the need for additional strategies. Beneficial bacteria application shows promise in AR, however most studies focus on oral probiotic administration without monitoring the applied strains in the upper respiratory tract (URT) and their local effects. In this randomized, double-blind, placebo-controlled trial, the probiotic Lacticaseibacillus rhamnosus GG was administered via chewable tablets in seasonal AR patients, randomized to probiotic (n=33) or placebo (n=31) groups. Per-protocol analysis of the URT microbiome, immune markers and AR symptoms was performed. L. rhamnosus GG trafficked from chewables to the oropharynx (77%, p=0.02) and nasopharynx (41%, p<0.0001). Control of self-reported AR symptoms via validated questionnaires under grass pollen exposure was observed after two weeks of probiotic administration and not upon placebo. A local decrease in salivary interleukin-4 (p < 0.05) and nasal IL-13 (p < 0.0001) was observed in the probiotic group. These data indicate that L. rhamnosus GG chewables can target the URT and exert local effects on key allergy cytokines after temporal probiotic engraftment. ImportanceAllergic rhinitis (AR) or hay fever is a highly prevalent condition, impacting nearly half the population in some countries. Supplementation of beneficial bacteria or probiotics has gained increasing attention in AR, and a key innovative way to do this is direct administration to the upper airways. Our study shows for the first time that the model probiotic strain Lacticaseibacillus rhamnosus GG can traffic to the nose in AR patients when administered via a slow-releasing chewable tablet. This trafficking is associated with local benefits in the airways, including on grass pollen-induced nasal symptoms and allergy-related cytokines.

microbiology↗

bioRxiv2023

Resource-efficient nitrogen removal from source separated urine with partial nitritation/anammox in a membrane aerated biofilm reactor

Source separation and decentralized urine treatment can cut costs in centralized wastewater treatment by diverting 80% of the nitrogen load in sewage. One promising approach for nitrogen removal in this context is partial nitritation/anammox (PN/A), reducing the aeration demand by 67% and organics dosage by 100% compared to nitrification/denitrification. Whilst previous studies with suspended biomass have encountered stability issues during PN/A treatment of urine, a PN/A biofilm was hypothesized to be more resilient. Its use for urine treatment was pioneered here for maximum rates and efficiencies in the energy efficient membrane-aerated biofilm reactor (MABR). Nitrogen removal rates of 1.0 g N L-1 d-1 and removal efficiencies of 80-95% were achieved during a 335-day stable operation at 28{degrees}C on stabilized (pH>11), diluted urine (10%). A balance between N2 and NO3 - formation was observed whilst optimizing the supply of O2 and was rate limiting for the conversion towards N2. Short-term operation on less- and undiluted urine yielded N removal rates of 0.6-0.8 g N L-1 d-1 and removal efficiencies of 93% on 66% urine and 85% on undiluted urine. Metataxonomic analysis and fluorescence in-situ hybridization confirmed the presence of biofilms consisting of nitrifiers (Nitrosomonas, Nitrospira) at the membrane side and anammox bacteria ("Candidatus Brocadia") at the anoxic bulk side. The findings suggest that a biofilm approach to PN/A treatment of urine overcomes stability issues, and a PN/A-MABR has significant potential for resource efficient decentralized treatment. In human long-duration deep-space missions, this gravity-independent technology could produce N2 to compensate artificial atmosphere losses whilst facilitating water recovery from urine. [GRAPHICAL ABSTRACT, COLOR] O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=101 SRC="FIGDIR/small/572732v1_ufig1.gif" ALT="Figure 1"> View larger version (39K): org.highwire.dtl.DTLVardef@1680b0corg.highwire.dtl.DTLVardef@1ad822dorg.highwire.dtl.DTLVardef@3d5c4borg.highwire.dtl.DTLVardef@764841_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioengineering↗

bioRxiv2022

Live biotherapeutic throat spray for respiratory virus inhibition and interferon pathway induction

Respiratory viruses such as influenza viruses, respiratory syncytial virus (RSV), and coronaviruses initiate infection at the mucosal surfaces of the upper respiratory tract (URT), where the resident respiratory microbiome has an important gatekeeper function. In contrast to gut-targeting administration of beneficial bacteria against respiratory viral disease, topical URT administration of probiotics is currently underexplored, especially for the prevention and/or treatment of viral infections. Here, we report the selection and formulation of a broad-acting throat spray with live lactobacilli which induce interferon regulatory pathways and are able to inhibit respiratory viruses. Rational selection of Lactobacillaceae strains was based on safety, applicability, and potential antiviral and immunostimulatory efficacy in the URT. Three strains, Lacticaseibacillus casei AMBR2, Lacticaseibacillus rhamnosus GG and Lactiplantibacillus plantarum WCFS1 significantly reduced the cytopathogenic effects of RSV, influenza A/H1N1 and B viruses, and HCoV-229E coronavirus in co-culture models with bacteria, virus and host cells. Subsequently, these strains were formulated in a throat spray and human monocytes were employed to confirm the formulation process did not reduce the interferon regulatory pathway-inducing capacity. Administration of the throat spray in healthy volunteers revealed that the lactobacilli were capable of temporary colonization of the throat in a metabolically active form.

microbiology↗

bioRxiv2018

Topical cream with live lactobacilli modulates the skin microbiome and reduce acne symptoms

The skin is home to an important part of our commensal microbiota, despite it being a cool, acidic and desiccated environment. Tailored microbiome modulation approaches with, for example probiotics, are highly challenging for this body site. Here we show by next-generating sequencing that Lactobacillus taxa -especially those known to be dominant in the human vagina- are underestimated members of the skin microbiota. Specific Lactobacillus strains were selected in the lab and formulated in a viable form in an oil in water-based topical cream. Facial application by patients with mild-to-moderate acne symptoms was able to reduce inflammatory lesions and comedone formation. This was associated with a temporary modulation of the skin microbiome, including a reduction in relative abundance of staphylococci and an increase in lactobacilli. Skin microbiome modulation by addition of carefully formulated lactobacilli seems to be new therapeutic option to reduce antibiotic use for common acne symptoms.

clinical trials↗