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Chronic endometritis (CE) is common in patients with infertility, and it is challenging to treat with antibiotics as bacteria often acquire resistance to the antibiotics, which leads to frequent recurrence of the condition. Probiotics, especially Lactobacillus species, are known for their usefulness in treating reproductive infections. This study evaluated Lactobacillus crispatus chen 01 (L. crispatus chen 01) isolated from healthy women who were 22-30 years old and married with children. In vitro experiments showed that L. crispatus chen 01 inhibited pathogens and reduced inflammation in CE mice by downregulating inflammatory proteins (TLR, MyD88, and p65/p-p65; L + Abx vs M, P < 0.01), improving histopathological features, and inhibiting bacterial growth. It also regulated endometrial processes, such as enhancing embryo implantation (BMP2 and Wnt4, L + Abx vs M, P < 0.01) via the Wnt/ß-catenin pathway, leading to increased pregnancy rates (L + Abx vs M, 100% vs 0%) in mice. In clinical trials, L. crispatus chen 01 improved progesterone levels (P = 0.0038), pregnancy rates (C vs Abx + L. c, 76.19% vs 87.18%), and pathological changes in CE patients. The findings from this study identify the administration of L. crispatus chen 01 as a promising intervention for CE that could improve pregnancy rates.
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Rosacea, a chronic inflammatory dermatological condition, is characterized by facial erythema and pustules. Recent investigations have delved into the interplay between the gut microbiota and rosacea pathogenesis, unveiling promising avenues for therapeutic intervention. In this study, we screened and isolated strains Ligilactobacillus salivarius 23-006 and Lacticaseibacillus paracasei 23-008 from the feces of healthy volunteers and evaluated the intervention effects of probiotics on rosacea by constructing an LL37 induced rosacea-like mouse model. Our results showed that both L. salivarius 23-006 and L. paracasei 23-008 were probiotic strains with favourable properties. In specific, we observed that both L. salivarius 23-006 and L. paracasei 23-008 alleviated skin lesions, reduced skin inflammatory infiltrates, and decreased the expression of inflammatory factors in mice, with the combination of L. salivarius 23-006 and L. paracasei 23-008 having the most significant effect. Moreover, the combination of strains reduced the expression of cathelicidin LL37 and rosacea-associated factors by inhibiting the TLR2/MyD88/NF-κB pathway. The 16S rRNA analysis showed that the combination enhanced the intestinal barrier, restored intestinal microbiota homeostasis, and up-regulated the abundance of Lactobacillus while down-regulating the abundance of Coprococcus and Oscillospira. We also explored the effects of postbiotics of L. salivarius 23-006 and L. paracasei 23-008 on rosacea. While postbiotics could also ameliorate the rosacea-like phenotype in mice via the TLR2/MyD88/NF-κB pathway, the effects were not as pronounced as those observed with probiotic treatment. However, the postbiotics still enhanced the intestinal barrier, up-regulated the Lactobacillus abundance, and modulated the intestinal microbiota. In conclusion, our study revealed that L. salivarius 23-006 and L. paracasei 23-008 improved rosacea by regulating the TLR2/MyD88/NF-κB pathway and intestinal microbiota, providing a theoretical basis for the treatment of rosacea.
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Catelicidinas , Factor 88 de Diferenciación Mieloide , FN-kappa B , Probióticos , Rosácea , Transducción de Señal , Receptor Toll-Like 2 , Probióticos/farmacología , Probióticos/administración & dosificación , Rosácea/microbiología , Animales , Factor 88 de Diferenciación Mieloide/metabolismo , Receptor Toll-Like 2/metabolismo , Ratones , FN-kappa B/metabolismo , Humanos , Ligilactobacillus salivarius/fisiología , Piel/microbiología , Péptidos Catiónicos Antimicrobianos , Femenino , Lacticaseibacillus paracasei/fisiología , Masculino , Modelos Animales de Enfermedad , Microbioma Gastrointestinal/efectos de los fármacos , Ratones Endogámicos C57BL , InflamaciónRESUMEN
Growing evidence have indicated the crucial role of intratumor microbiome in a variety of solid tumor. However, the intratumoral microbiome in gynecological malignancies is largely unknown. In the present study, a total of 90 Han patients, including 30 patients with cancer in cervix, ovary, and endometrium each were enrolled, the composition of intratumoral microbiome was assessed by 16S rDNA amplicon high throughput sequencing. We found that the diversity and metabolic potential of intratumoral microbiome in all three cancer types were very similar. Furthermore, all three cancer types shared a few taxa that collectively take up high relative abundance and positive rate, including Pseudomonas sp., Comamonadaceae gen. sp., Bradyrhizobium sp., Saccharomonospora sp., Cutibacterium acnes, Rubrobacter sp., Dialister micraerophilus, and Escherichia coli. Additionally, Haemophilus parainfluenzae and Paracoccus sp. in cervical cancer, Pelomonas sp. in ovarian cancer, and Enterococcus faecalis in endometrial cancer were identified by LDA to be a representative bacterial strain. In addition, in cervical cancer patients, alpha-fetoprotein (AFP) (correlation coefficient = -0.3714) was negatively correlated (r = 0.4, 95% CI: 0.03 to 0.7) with Rubrobacter sp. and CA199 (correlation coefficient = 0.3955) was positively associated (r = 0.4, 95% CI: 0.03 to 0.7) with Saccharomonospora sp.. In ovarian cancer patients, CA125 (correlation coefficient = -0.4451) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.09) with Porphyromonas sp.. In endometrial cancer patients, CEA (correlation coefficient = -0.3868) was negatively correlated (r = -0.4, 95% CI: -0.7 to -0.02) with Cutibacterium acnes. This study promoted our understanding of the intratumoral microbiome in gynecological malignancies.IMPORTANCEIn this study, we found the compositional spectrum of tumor microbes among gynecological malignancies were largely similar by sharing a few taxa and differentiated by substantial species owned uniquely. Certain species, mostly unreported, were identified to be associated with clinical characteristics. This study prompted our understanding of gynecological malignancies and offered evidence for tumor microbes affecting tumor biology among cancers in the female reproductive system.
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As a chemotherapy agent, cisplatin (DDP) is often associated with drug resistance and gastrointestinal toxicity, factors that severely limit therapeutic efficacy in patients with ovarian cancer (OC). Naringin has been shown to increase sensitivity to cisplatin, but whether the intestinal microbiota is associated with this effect has not been reported so far. In this study, we applied a humanized mouse model for the first time to evaluate the reversal of cisplatin resistance by naringin, as well as naringin combined with the microbiota in ovarian cancer. The results showed that naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 had an inhibitory effect on the tumor, significantly reducing tumor size (p<0.05), as well as the concentrations of serum tumor markers CA125 and HE4, increased the relative abundance of Bifidobacterium and Bacteroides, inhibit Toll-like receptor 4 (TLR4)/nuclear factor κB (NF-κB)-induced intestinal inflammation and increase the expression of intestinal permeability-associated proteins ZO-1 (p<0.001) and occludin (p<0.01). In conclusion, the above data demonstrate how naringin combined with Bifidobacterium animalis subsp. lactis NCU-01 reverses cisplatin resistance in ovarian cancer by modulating the intestinal microbiota, inhibiting the TLR4/NF-κB signaling pathway and modulating the p38MAPK signaling pathway.
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Female genital tract infection with high-risk human papilloma virus (HR-HPV) has the risk of developing into cervical cancer, and there is still a lack of effective therapeutic strategies. Probiotic intervention is considered as a potential intervention for HR-HPV, while exploration into living probiotic preparations for specific diseases remains limited and insufficient. This prospective controlled pilot study was conducted to observe the effect of intravaginal transplantation of a vaginal isolated natural probiotic strain, Lactobacillus crispatus chen-01, on the clearance of high-risk HPV infection. 100 women with high-risk HPV infection were enrolled and randomly divided into placebo group and probiotic treatment group, which received intravaginal transplantation of L. crispatus chen-01. Cervical exfoliated cells were collected 6 months later for detecting DNA load, typing of HPV, and cytological analysis. Our results showed that vaginal transplantation with L. crispatus chen-01 significantly reduced viral load of HPV, ameliorated HPV clearance rate, and improved vaginal inflammation state without causing obvious adverse reactions. Analysis of 16S rRNA sequencing revealed that L. crispatus chen-01 could effectively reconstitute the vaginal microbiota in women with high-risk HPV, which might be one of the underlying mechanisms of the beneficial effect of L. crispatus chen-01 transplantation. Our results suggested that vaginal transplantation of L. crispatus chen-01 might be a promising treatment for patients with high-risk HPV infection.
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Lactobacillus crispatus , Infecciones por Papillomavirus , Probióticos , Vagina , Femenino , Humanos , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Infecciones por Papillomavirus/terapia , Infecciones por Papillomavirus/virología , Proyectos Piloto , Lactobacillus crispatus/aislamiento & purificación , Vagina/microbiología , Vagina/virología , Adulto , Estudios Prospectivos , Administración Intravaginal , Carga Viral , Persona de Mediana Edad , Papillomaviridae/genética , Papillomaviridae/aislamiento & purificación , MicrobiotaRESUMEN
Cancer presents a formidable challenge in modern medicine due to the intratumoral heterogeneity and the dynamic microenvironmental niche. Natural or genetically engineered oncolytic bacteria have always been hailed by scientists for their intrinsic tumor-targeting and oncolytic capacities. However, the immunogenicity and low toxicity inevitably constrain their application in clinical practice. When nanomaterials, characterized by distinctive physicochemical properties, are integrated with oncolytic bacteria, they achieve mutually complementary advantages and construct efficient and safe nanobiohybrids. In this review, we initially analyze the merits and drawbacks of conventional tumor therapeutic approaches, followed by a detailed examination of the precise oncolysis mechanisms employed by oncolytic bacteria. Subsequently, we focus on harnessing nanomaterial-assisted oncolytic bacteria (NAOB) to augment the effectiveness of tumor therapy and utilizing them as nanotheranostic agents for imaging-guided tumor treatment. Finally, by summarizing and analyzing the current deficiencies of NAOB, this review provides some innovative directions for developing nanobiohybrids, intending to infuse novel research concepts into the realm of solid tumor therapy.
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Diarrhea of college students (DCS) is a prevalent issue among college students, affecting their daily lives and academic performance. This study aims to explore the potential effect of Bifidobacterium breve BB05 supplements on the DCS. Initially, fifty healthy and fifty diarrheal students were recruited in the observational experiment and allocated into control and diarrhea groups, respectively. Subsequently, one hundred diarrheal students were newly recruited in the intervention experiment and randomly allocated into placebo and probiotic groups, both treated for 2 weeks. Questionnaires (BSS, HAMA-14, and HDRS-17) were performed to assess the students' diarrheal states and mental health at baseline and post-treatment. Fecal samples underwent 16S rRNA sequencing and Enzyme-Linked Immunosorbent Assay to evaluate gut microbiota and fecal metabolite alternations. Results indicated that B. breve BB05 supplementation significantly enriched (p < 0.05) the reduced gut microbial diversity caused by diarrhea. Diarrhea resulted in notable alterations in gut microbiota composition, as exhibited by elevated Collinsella and Streptococcus, alongside substantially decreased Bifidobacterium, Bacteroides, and Prevotella, while B. breve BB05 supplementation partially restored the compromised gut microbiota at both the phylum and genus levels, particularly by increasing Bifidobacterium and Roseburia (p < 0.05). Importantly, questionnaire results suggested that B. breve BB05 administration achieved superior efficacy in relieving diarrhea symptoms and the associated anxiety and depression in college students. An increased fecal concentration of 5-hydroxytryptamine (5-HT) was also observed in the probiotic group, while Acetylcholine (ACH), Epinephrine (EPI), and Noradrenaline/Norepinephrine (NANE) reduced, revealing the potential of B. breve BB05 in alleviating anxiety and depression via modulating the microbiota-gut-brain axis. Furthermore, correlation analysis suggested that the altered microbiota and fecal neurotransmitters were closely associated with the mental symptoms. These results endorse B. breve BB05 intervention as a promising and innovative approach to alleviate both diarrhea and mental health conditions among college students.
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Bifidobacterium breve , Diarrea , Heces , Microbioma Gastrointestinal , Probióticos , Estudiantes , Humanos , Diarrea/microbiología , Diarrea/terapia , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Método Doble Ciego , Masculino , Estudiantes/psicología , Femenino , Adulto Joven , Heces/microbiología , Universidades , AdultoRESUMEN
Population aging is a substantial challenge for the global sanitation framework. Unhealthy aging tends to be accompanied by chronic diseases such as cardiovascular disease, diabetes, and cancer, which undermine the welfare of the elderly. Based on the fact that aging is inevitable but retarding aging is attainable, flexible aging characterization and efficient anti-aging become imperative for healthy aging. The gut microbiome, as the most dynamic component interacting with the organism, can affect the aging process through its own structure and metabolites, thus holding the potential to become both an ideal aging-related biomarker and an intervention strategy. This review summarizes the value of applying gut microbiota as aging-related microbial biomarkers in diagnosing aging state and monitoring the effect of anti-aging interventions, ultimately pointing to the future prospects of microbial intervention strategies in maintaining healthy aging.
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Gastrointestinal symptoms constitute a frequent complication in postoperative patients with valvular heart disease (VHD), impacting their postoperative recovery. Probiotics contribute to regulating human gut microbiota balance and alleviating postoperative gastrointestinal symptoms. Our objective involved assessing the potential of Bifidobacterium animalis subsp. lactis LPL-RH to alleviate postoperative gastrointestinal symptoms and expedite patient recovery. Adult patients diagnosed with VHD scheduled for valve surgery were enrolled. 110 patients were randomly divided into two groups and received LPL-RH or a placebo for 14 days. Gastrointestinal symptoms were evaluated using the Gastrointestinal Symptoms Questionnaire. An analysis of the time to recovery of bowel function and various postoperative variables was conducted in both study groups. Variations in the intestinal microbiota were detected via 16S rRNA sequencing. The study was completed by 105 participants, with 53 in the probiotic group and 52 in the placebo group. Compared to the placebo group, LPL-RH significantly reduced the total gastrointestinal symptom score after surgery (p = 0.004). Additionally, LPL-RH was found to significantly reduce abdominal pain (p = 0.001), bloating (p = 0.018), and constipation (p = 0.022) symptom scores. Furthermore, LPL-RH dramatically shortened the time to recovery of bowel function (p = 0.017). Moreover, LPL-RH administration significantly enhanced patients' postoperative nutrition indexes (red blood cell counts, hemoglobin level, p < 0.05). Microbiome analysis showed that the composition and diversity of the postoperative intestinal microbiota differed between the probiotic and placebo groups. No adverse incidents associated with probiotics were documented, emphasizing their safety. This study initially discovered that oral B. animalis subsp. lactis LPL-RH can assist in regulating intestinal microbiota balance, alleviating gastrointestinal symptoms, promoting intestinal function recovery, and enhancing nutrition indexes in patients with VHD after surgery. Regulating the intestinal microbiota may represent a potential mechanism for LPL-RH to exert clinical benefits.
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Bifidobacterium animalis , Microbioma Gastrointestinal , Enfermedades de las Válvulas Cardíacas , Probióticos , Humanos , Microbioma Gastrointestinal/efectos de los fármacos , Masculino , Femenino , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Probióticos/farmacología , Persona de Mediana Edad , Enfermedades de las Válvulas Cardíacas/cirugía , Adulto , Complicaciones Posoperatorias/microbiología , Anciano , Enfermedades Gastrointestinales , Método Doble CiegoRESUMEN
Helicobacter pylori is a prevalent bacterial pathogen globally, implicated in various gastrointestinal disorders. Current recommended antibiotic therapies for H. pylori infection have been proven to be therapeutically insufficient, with low eradication rates and high recurrence rates. Emerging evidence suggests that antibiotic therapy for H. pylori can lead to gastrointestinal and subsequent vaginal dysbiosis, posing challenges for conventional antibiotic approaches. Thus, this article proposes a novel probiotic therapy involving simultaneous oral and intra-vaginal probiotic administration alongside antibiotics for H. pylori treatment, aiming to enhance eradication rates and mitigate dysbiosis. We begin by providing an overview of gastrointestinal and vaginal microbiota and their interconnectedness through the vagina-gut axis. We then review the efficacy of current antibiotic regimens for H. pylori and discuss how antibiotic treatment impacts the vaginal microenvironment. To explore the feasibility of this approach, we evaluate the effectiveness of oral and intra-vaginal probiotics in restoring normal microbiota in the gastrointestinal and vaginal tracts, respectively. Additionally, we analyze the direct mechanisms by which oral and intra-vaginal probiotics act on their respective tracts and discuss potential cross-tract mechanisms. Considering the potential synergistic therapeutic effects of probiotics in both the gastrointestinal and vaginal tracts, dual-channel probiotic therapy holds promise as a more effective approach for H. pylori eradication and dysbiosis mitigation, presenting a novel concept in the collaborative treatment of gastrointestinal and genital disorders.
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Antibacterianos , Disbiosis , Infecciones por Helicobacter , Helicobacter pylori , Probióticos , Vagina , Probióticos/administración & dosificación , Femenino , Humanos , Disbiosis/terapia , Antibacterianos/administración & dosificación , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/terapia , Infecciones por Helicobacter/microbiología , Vagina/microbiología , Vagina/efectos de los fármacos , Helicobacter pylori/efectos de los fármacos , Administración Intravaginal , Administración OralRESUMEN
The high prevalence of constipation after fracture surgery brings intolerable discomfort to patients on the one hand, and affects post-surgery nutrient absorption on the other hand, resulting in poor prognosis. Given the acknowledged probiotic properties of Lactobacillus rhamnosus, 100 fracture patients with post-surgery constipation were centrally enrolled and administered orally with L. rhamnosus JYLR-127 to assess the efficacy of probiotic-adjuvant therapy in alleviating post-fracture constipation symptoms. The results showed that L. rhamnosus JYLR-127 improved fecal properties, promoted gastrointestinal recovery, and relieved constipation symptoms, which were mainly achieved by elevating Firmicutes (p < 0.01) and descending Bacteroidetes (p < 0.001), hence remodeling the disrupted intestinal microecology. In addition, blood routine presented a decrease in C-reactive protein levels (p < 0.05) and an increase in platelet counts (p < 0.05) after probiotic supplementation, prompting the feasibility of L. rhamnosus JYLR-127 in anti-inflammation, anti-infection and hemorrhagic tendency prevention after fracture surgery. Our study to apply probiotics in ameliorating constipation after fracture surgery is expected to bless the bothered patients, and provide broader application scenarios for L. rhamnosus preparations.
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Estreñimiento , Fracturas Óseas , Lacticaseibacillus rhamnosus , Complicaciones Posoperatorias , Probióticos , Humanos , Estreñimiento/terapia , Probióticos/uso terapéutico , Probióticos/administración & dosificación , Femenino , Masculino , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Método Simple Ciego , Fracturas Óseas/cirugía , Fracturas Óseas/complicaciones , Adulto , Microbioma Gastrointestinal , Heces/microbiología , Anciano , Resultado del TratamientoRESUMEN
Cadmium (Cd) is recognized as being linked to several liver diseases. Currently, due to the limited spectrum of drugs available for the treatment of Cd intoxication, developing and designing antidotes with superior detoxification capacity and revealing their underlying mechanisms remains a major challenge. Therefore, we developed the first next-generation probiotic E. coli 1917-pSK18a-MT that delivers metallothionein (MT) to overcome Cd-induced liver injury in C57BL/6 mice by utilizing bacterial surface display technology. The results demonstrate that E. coli 1917-pSK18a-MT could efficiently express MT without altering the growth and probiotic properties of the strain. Moreover, we found that E. coli 1917-pSK18a-MT ameliorated Cd contamination-induced hepatic steatosis, inflammatory cell infiltration, and liver fibrosis by decreasing the expression of aminotransferases along with inflammatory factors. Activation of the Nrf2-Keap1 signaling pathway also further illustrated the hepatoprotective effects of the engineered bacteria. Finally, we showed that E. coli 1917-pSK18a-MT improved the colonic barrier function impaired by Cd induction and ameliorated intestinal flora dysbiosis in Cd-poisoned mice by increasing the relative abundance of the Verrucomicrobiota. These data revealed that the combination of E. coli 1917 and MT both alleviated Cd-induced liver injury to a greater extent and restored the integrity of colonic epithelial tissues and bacterial dysbiosis.
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Cadmio , Enfermedad Hepática Inducida por Sustancias y Drogas , Escherichia coli , Microbioma Gastrointestinal , Metalotioneína , Ratones Endogámicos C57BL , Probióticos , Animales , Probióticos/farmacología , Microbioma Gastrointestinal/efectos de los fármacos , Metalotioneína/metabolismo , Cadmio/toxicidad , Ratones , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Disbiosis , Masculino , Hígado/efectos de los fármacos , Hígado/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Aging is a degenerative disease in which organisms and neurological functions decline. Emerging research has underscored the vital role of the gut microbiota in age-related processes. However, the identification of aging-associated core microbiota remains limited. In this investigation, we isolated a strain of B. pseudocatenulatum NCU-08 from the feces of centenarians and assessed its impact on aging using a mouse model induced by D-gal. Our study revealed the exceptional probiotic attributes of B. pseudocatenulatum NCU-08. Administration of B. pseudocatenulatum NCU-08 significantly ameliorated age-related memory impairment, motor dysfunction, and anxiety-like behaviors in aging mice (p < 0.01). Moreover, tissue staining analysis demonstrated that B. pseudocatenulatum NCU-08 reduced the intensity of SA-ß-gal-positive in the hippocampus of aging mice. It also reversed pathological damage and structural abnormalities in brain and intestinal tissue. B. pseudocatenulatum NCU-08 inhibited neuroinflammation induced by TLR4/NF-κB (p < 0.01) and preserved the blood-brain barrier integrity by activating the AMPK/Sirt1 pathway (p < 0.05). Furthermore, it mitigated neuronal apoptosis and oxidative stress by upregulating the PI3K/AKT signaling pathway (p < 0.01) and enhancing the activities of antioxidant enzymes, including GSH-Px (p < 0.01), SOD (p < 0.01), and CAT (p < 0.01). Besides, analysis of 16S rRNA sequencing data demonstrated that treatment with B. pseudocatenulatum NCU-08 restored intestinal microbiota homeostasis after senescence. It enhanced the abundance of beneficial bacteria while suppressing the growth of pathogenic microorganisms. In summary, our study unveiled that this novel strain of B. pseudocatenulatum NCU-08 exerts anti-aging effects through regulating the AMPK/Sirt1 pathway and intestinal microbiota. It holds promise as a functional food for promoting anti-aging effects and offers a novel approach to address aging and associated metabolic disorders.
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Proteínas Quinasas Activadas por AMP , Envejecimiento , Bifidobacterium , Microbioma Gastrointestinal , Probióticos , Transducción de Señal , Sirtuina 1 , Animales , Microbioma Gastrointestinal/efectos de los fármacos , Sirtuina 1/metabolismo , Sirtuina 1/genética , Ratones , Probióticos/farmacología , Transducción de Señal/efectos de los fármacos , Masculino , Proteínas Quinasas Activadas por AMP/metabolismo , Humanos , Ratones Endogámicos C57BL , Hipocampo/metabolismo , Hipocampo/efectos de los fármacosRESUMEN
Immune checkpoint blockade (ICB) has revolutionized cancer therapy but only works in a subset of patients due to the insufficient infiltration, persistent exhaustion, and inactivation of T cells within a tumor. Herein, we develop an engineered probiotic (interleukin [IL]-12 nanoparticle Escherichia coli Nissle 1917 [INP-EcN]) acting as a living drug factory to biosynthesize anti-PD-1 and release IL-12 for initiating systemic antitumor immunity through T cell cascade regulation. Mechanistically, INP-EcN not only continuously biosynthesizes anti-PD-1 for relieving immunosuppression but also effectively cascade promote T cell activation, proliferation, and infiltration via responsive release of IL-12, thus reaching a sufficient activation threshold to ICB. Tumor targeting and colonization of INP-EcNs dramatically increase local drug accumulations, significantly inhibiting tumor growth and metastasis compared to commercial inhibitors. Furthermore, immune profiling reveals that anti-PD-1/IL-12 efficiently cascade promote antitumor effects in a CD8+ T cell-dependent manner, clarifying the immune interaction of ICB and cytokine activation. Ultimately, such engineered probiotics achieve a potential paradigm shift from T cell exhaustion to activation and show considerable promise for antitumor bio-immunotherapy.
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Interleucina-12 , Probióticos , Receptor de Muerte Celular Programada 1 , Animales , Interleucina-12/metabolismo , Probióticos/farmacología , Ratones , Receptor de Muerte Celular Programada 1/metabolismo , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Humanos , Ratones Endogámicos C57BL , Línea Celular Tumoral , Linfocitos T/inmunología , Linfocitos T/metabolismo , Linfocitos T CD8-positivos/inmunología , Linfocitos T CD8-positivos/metabolismo , Escherichia coli/metabolismo , Neoplasias/inmunología , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Nanopartículas , Femenino , Activación de Linfocitos/efectos de los fármacos , Activación de Linfocitos/inmunologíaRESUMEN
BACKGROUND: Depression affects a significant portion of the global population and has emerged as one of the most debilitating conditions worldwide. Recent studies have explored the relationship between depression and the microbiota of the intestine, revealing potential avenues for effective treatment. METHODS: To evaluate the potential alleviation of depression symptoms, we employed a depression C57BL/6 mice model induced by chronic unpredictable mild stress (CUMS). We administered Lactiplantibacillus plantarum JYLP-326 and conducted various animal behavior tests, including the open-field test (OFT), sucrose preference test (SPT), and tail-suspension test (TST). Additionally, we conducted immunohistochemistry staining and analyzed the hippocampal and colon parts of the mice. RESULTS: The results of the behavior tests indicated that L. plantarum JYLP-326 alleviated spontaneous behavior associated with depression. Moreover, the treatment led to significant improvements in GFAP and Iba1, suggesting its potential neuroprotective effects. Analysis of the hippocampal region indicated that L. plantarum JYLP-326 administration upregulated p-TPH2, TPH2, and 5-HT1AR, while downregulating the expression of pro-inflammatory cytokines IL-1ß, IL-6, and TNF-α. In the colon, the treatment inhibited the TLR4-MyD88-NF-κB pathway and increased the levels of occludin and ZO-1, indicating improved intestinal barrier function. Additionally, the probiotic demonstrated a regulatory effect on the HMGB1-RAGE-TLR4 signaling pathway. CONCLUSIONS: Our findings demonstrate that L. plantarum JYLP-326 exhibits significant antidepressant-like effects in mice, suggesting its potential as a therapeutic approach for depression through the modulation of gut microbiota. However, further investigations and clinical trials are required to validate its safety and efficacy for human use.
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Depresión , Microbioma Gastrointestinal , Humanos , Ratones , Animales , Depresión/tratamiento farmacológico , Depresión/etiología , Receptor Toll-Like 4/metabolismo , Disbiosis/tratamiento farmacológico , Disbiosis/metabolismo , Ratones Endogámicos C57BL , Antidepresivos/farmacología , Antidepresivos/uso terapéutico , Antidepresivos/metabolismo , Hipocampo/metabolismo , Estrés Psicológico/complicaciones , Estrés Psicológico/tratamiento farmacológico , Estrés Psicológico/metabolismo , Modelos Animales de EnfermedadRESUMEN
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.
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Gastrointestinal symptoms are a common postoperative complication in patients with congenital heart disease (CHD), affecting their postoperative recovery. Probiotic intervention may be a promising therapeutic approach to alleviate postoperative gastrointestinal symptoms. This study aimed to evaluate the potential of Lactobacillus plantarum 24-7 (L. plantarum 24-7) in mitigating postoperative gastrointestinal symptoms and promoting patient recovery. Adult CHD patients scheduled for surgical intervention were recruited. One hundred and twenty patients were randomized and received L. plantarum or placebo intervention twice daily for ten days. Gastrointestinal symptoms were assessed utilizing the Gastrointestinal Symptom Rating Scale (GSRS). Various postoperative variables were analyzed across both groups. Alterations in gut microbiota were evaluated through 16S rRNA sequencing. 112 patients completed the study, with 55 in the probiotic group and 57 in the placebo group. While the disparity in overall postoperative GSRS scores between the two groups did not reach statistical significance (P = 0.067), marked differences were observed in bloating (P = 0.004) and hard stool (P = 0.030) scores. Furthermore, individuals within the probiotic group exhibited lower postoperative neutrophil counts (P = 0.007) and concurrently higher lymphocyte counts (P = 0.001). Variations in the diversity and composition of postoperative gut microbiota were discerned between the probiotic and placebo groups. Remarkably, no probiotic-related adverse events were documented. Supplementation with L. plantarum was well-tolerated and demonstrated partial efficacy in ameliorating gastrointestinal symptoms in postoperative CHD patients. Modulating the gut microbiota may be a potential mechanism by which L. plantarum exerts clinical benefits.
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Microbioma Gastrointestinal , Cardiopatías Congénitas , Lactobacillus plantarum , Probióticos , Adulto , Humanos , ARN Ribosómico 16S , Probióticos/uso terapéutico , Cardiopatías Congénitas/cirugíaRESUMEN
Ovarian cancer poses a significant threat to women's health, with conventional treatment methods encountering numerous limitations, and the emerging engineered bacterial anti-tumor strategies offer newfound hope for ovarian cancer treatment. In this study, we constructed the VNP20009-Abvec-Igκ-MIIP (VM) engineered strain and conducted initial assessments of its in vitro growth performance and the expression capability of migration/invasion inhibitory protein (MIIP). Subsequently, ID8 ovarian cancer cells and mouse cancer models were conducted to investigate the impact of VM on ovarian cancer. Our results revealed that the VM strain demonstrated superior growth performance, successfully invaded ID8 ovarian cancer cells, and expressed MIIP, consequently suppressing cell proliferation and migration. Moreover, VM specifically targeted tumor sites and expressed MIIP which further reduced the tumor volume of ovarian cancer mice (p < 0.01), via the downregulation of epidermal growth factor receptor (EGFR), Ras, p-MEK, and p-ERK. The downregulation of the PI3K/AKT signaling pathway and the decrease in Bcl-2/Bax levels also indicated VM's apoptotic potency on ovarian cancer cells. In summary, our research demonstrated that VM exhibits promising anti-tumor effects both in vitro and in vivo, underscoring its potential for clinical treatment of ovarian cancer. KEY POINTS: ⢠This study has constructed an engineered strain of Salmonella typhimurium capable of expressing anticancer proteins ⢠The engineered bacteria can target and colonize tumor sites in vivo ⢠VM can inhibit the proliferation, migration, and invasion of ovarian cancer cells.
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Vacunas Bacterianas , Neoplasias Ováricas , Fosfatidilinositol 3-Quinasas , Humanos , Femenino , Animales , Ratones , Neoplasias Ováricas/terapia , Transducción de Señal , Modelos Animales de Enfermedad , Quinasas de Proteína Quinasa Activadas por MitógenosRESUMEN
Proton pump inhibitors (PPIs) are currently routinely used for the treatment of reflux esophagitis (RE); however, with frequent symptom recurrence after discontinuation and limited clinical improvement in accompanying gastrointestinal symptoms. This study aims to explore the adjuvant therapeutic effect of Bifidobacterium supplement for RE patients. A total of 110 eligible RE patients were recruited and randomly assigned to the placebo and probiotic groups. All patients were treated with rabeprazole tablets and simultaneously received either Bifidobacterium animalis subsp. lactis MH-02 or placebo for 8 weeks. Patients who achieved clinical remission then entered the next 12 weeks of follow-up. RDQ, GSRS scores, and endoscopy were performed to assess clinical improvement, and changes in intestinal microbiota were analyzed with high-throughput sequencing. Our results revealed that MH-02 combined therapy demonstrated an earlier time to symptom resolution (50.98% vs. 30.61%, p = 0.044), a significant reduction in the GSRS score (p = 0.0007), and a longer mean time to relapse (p = 0.0013). In addition, high-throughput analyses showed that MH-02 combined therapy increased the α (p = 0.001) diversity of gut microbiota and altered microbial composition by beta diversity analysis, accompanied with significantly altered gut microbiota taxa at the genus level, where the abundance of some microbial genera including Bifidobacterium, Clostridium, and Blautia were increased, while the relative abundance of Streptococcus and Rothia were decreased (p < 0.05). Collectively, these results support the beneficial effects of MH-02 as a novel complementary strategy in RE routine treatment.