Live Lactobacillus Research Articles

Lactobacillus crispatus-Mediated Gut-Reproductive Tract Axis-Alleviated Microbial Dysbiosis and Oviductal Inflammation in a Laying Hen Model.

Oviductal inflammation (OI) significantly reduces the egg production and economic returns in poultry farming. While Lactobacillus crispatus (LAC) is effective against inflammation, its role in treating or preventing oviductal inflammation is understudied. In this study, we investigated the therapeutic mechanisms of LAC on oviductal inflammation, with a focus on reproductive tract health, microbiome, gene expression, and cytokine levels. This study involved 24 Jingfen No. 6 laying hens aged 60 weeks, divided into four groups: the CON, OI, OI + LAC, and OI + heat-killed Lactobacillus crispatus (HLAC) groups. And it included a 10-day adaptation, a 7-day period for the development of OI using inflammation-inducing drugs (the control received saline), followed by an 8-day treatment in which the CON and OI groups received 1 mL of MRS broth daily, and the OI + LAC and OI + HLAC groups were treated with live and heat-killed Lactobacillus crispatus (109 CFUs/mL), respectively, with six hens in each group. This study showed that Lactobacillus crispatus supplementation significantly reduced the oviductal inflammation and atrophy in the hens, with the affected hens showing markedly lower egg production rates (p < 0.001) compared to the control and treated groups (OI + HLAC and OI + LAC). The daily intake of fresh (OI + LAC, p = 0.076) or heat-killed (OI + HLAC, p < 0.01) Lactobacillus crispatus notably enhanced the feed conversion efficiency. The OI group suffered significant ovarian damage and vascular rupture, more so than the CON group, while Lactobacillus crispatus supplementation mitigated this damage. The IL-1β, IL-6, and IL-8 levels were significantly elevated in the OI group compared to those in the OI + LAC group (p < 0.05), with a significant reduction in the TNF-α levels in the latter (p < 0.001). The supplementation improved the microbial composition in the cecum, isthmus, and shell gland, enriching the cecum with beneficial bacteria, such as Ruminococcus_torques_group and Megamonas. This approach fostered ovarian health and follicle differentiation and preserved the epithelial cell barrier function in the shell gland, reducing inflammatory damage in the genital tract. This dual efficacy underscores the role of the probiotic in diminishing oviductal inflammation, regardless of its state.

Upregulation of Immune checkpoint PD-L1 in Colon cancer cell lines and activation of T cells by Leuconostoc mesenteroides

Globally colorectal cancer ranks as the third most widespread disease and the third leading cause of cancer-associated mortality. Immunotherapy treatments like PD-L1 blockade have been used to inhibit the PD-L1 legend, which boosts the activity of cytotoxic T lymphocytes. Recently, studies suggest that some probiotics could potentially enhance the effectiveness of immunotherapy treatments for cancer patients. We found that in Caco-2 and HT-29 cells, the live Leuconostoc mesenteroides treatment resulted an increase in the PD-L1 expression and this treatment stimulated interferon-gamma (IFN-γ) production in Jurkat T-cells. Due to the well-established ability of IFN-γ to enhance PD-L1 expression, the combination of IFN-γ and L. mesenteroides was used in colon cancer cell lines and a resulting remarkable increase of over tenfold in PD-L1 expression was obtained. Interestingly, when L. mesenteroides and IFN-γ are present, the blockage of PD-L1 using PD-L1 antibodies not only improved the viability of Jurkat T-cells but also significantly boosted the levels of IFN-γ and IL-2, the T-cells activation marker cytokines. In addition to upregulating PD-L1, L. mesenteroides also activated Toll-like receptors (TLRs) and NOD-like receptors (NODs) pathways, specifically through TLR2 and NOD2, while also exerting a suppressive effect on autophagy in colon cancer cell lines. In conclusion, our findings demonstrate a significant upregulation of PD-L1 expression in colon cancer cells upon co-culturing with L. mesenteroides. Moreover, the presence of PD-L1 antibodies during co-culturing activates Jurkat T cells. The observed enhancement in PD-L1 expression may be attributed to the inhibition of the Autophagy pathway or activation of the hippo pathway.Graphical abstract textThe administration of Live Lactobacillus mesenteroides on colon cancer cells leads to the elevation of PD-L1, with a further increase observed in the presence of IFN-γ. Co-cultivation of Live L. mesenteroides with colon cancer cells in conjunction with anti-PD-L1 blockade antibody results in the enhanced viability of T cells.Key PointsCo-culturing L. mesenteroides increases PD-L1 gene and protein transaction in colon cancer.L. mesenteroides existing enhances T cells viability and activity.GPCR41/42 is a possible link between L. mesenteroides, YAP-1 and PD-L1.

Effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the Structure and Function of the Intestinal Flora in Rabbits Undergoing Hepatic Artery Infusion Chemotherapy.

Few studies have explored the biological mechanism by which probiotics alleviate adverse reactions to chemotherapy drugs after local hepatic chemotherapy perfusion by regulating the intestinal flora. This study investigates the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the intestinal microbial structure and intestinal barrier function, as well as the potential mechanism in rabbits after local hepatic chemotherapy infusion. Eighteen New Zealand White rabbits were randomly divided into a control group, a hepatic local chemotherapy perfusion group, and a hepatic local chemotherapy perfusion + Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets group to assess the effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets on the adverse reactions. The administration of Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets alleviated the intestinal flora disorder caused by local hepatic perfusion chemotherapy, promoted the growth of beneficial bacteria, and inhibited the growth of harmful bacteria. The Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets also reduced the levels of serum pro-inflammatory cytokines and liver injury factors induced by local hepatic perfusion chemotherapy. Our findings indicate that Combined Live Bifidobacterium, Lactobacillus, Enterococcus, and Bacillus Cereus Tablets can ameliorate the toxicity and side effects of chemotherapy by regulating intestinal flora, blocking pro-inflammatory cytokines, reducing liver injury factors, and repairing the intestinal barrier. Probiotics may be used as a potential alternative therapeutic strategy to prevent the adverse reactions caused by chemotherapy with local hepatic perfusion.

Origin of the neonatal gut microbiota and probiotic intervention: a randomized controlled trial.

This study aims to evaluate the origin of the neonatal gut microbiota on the 14th day and probiotic intervention in the third trimester. Samples were obtained from a total of 30 pregnant individuals and their offspring, divided into a control group with no intervention and a probiotic group with live combined Bifidobacterium and Lactobacillus tablets, analyzing by 16S rRNA amplicon sequencing of the V4 region to evaluate the composition of them. Non-metric multidimensional scaling and SourceTracker were used to evaluate the origin of neonatal gut microbiota. We found that the microbiota in the neonatal gut at different times correlated with that in the maternal microbiota. The placenta had more influence on meconium microbiota. Maternal gut had more influence on neonatal gut microbiota on the 3rd day and 14th day. We also found that the maternal gut, vaginal, and placenta microbiota at full term in the probiotic group did not have a significantly different abundance of Bifidobacterium, Lactobacillus, or Streptococcus. However, some other bacteria changed in the maternal gut and their neonatal gut in the probiotic group.

Lactobacillus casei Shirota probiotic drinks reduce antibiotic associated diarrhoea in patients with spinal cord injuries who regularly consume proton pump inhibitors: a subgroup analysis of the ECLISP multicentre RCT

Study designThis was a sub-group analysis of a multicentre, randomised, placebo-controlled, double-blind trial (ECLISP trial)ObjectivesTo assess the efficacy of a probiotic containing at least 6.5 × 109 live Lactobacillus casei Shirota (LcS) in preventing antibiotic associated diarrhoea (AAD) in patients with spinal cord injury (SCI) who consumed proton pump inhibitor (PPI) regularly. LcS or placebo was given once daily for the duration of an antibiotic course and continued for 7 days thereafter. The trial was registered with ISRCTN:13119162.SettingThree SCI centres (National Spinal Injuries Centre, Midland Centre for Spinal Injuries and Princess Royal Spinal Cord Injuries Centre) in the United KingdomMethodsBetween November 2014, and November 2019, 95 eligible consenting SCI patients (median age: 57; IQ range: 43-69) were randomly allocated to receive LcS (n = 50) or placebo (n = 45). The primary outcome is the occurrence of AAD up to 30 days after finishing LcS/placebo.ResultsThe LcS group had a significantly lower incidence of AAD at 30 days after finishing the antibiotic course (28.0 v 53.3%, RR: 95% CI: 0.53, 0.31–0.89; z = 2.5, p = 0.01). Multivariate logistic regression analysis identified that LcS can reduce the risk of AAD at 30 days (OR: 0.36, 95% CI 0.13, 0.99, p < 0.05). No intervention-related adverse events were reported during the study.ConclusionsLcS has the potential to prevent AAD in what could be considered a defined vulnerable group of SCI patients on regular PPI. A confirmatory, randomised, placebo-controlled study is needed to confirm this apparent therapeutic success to translate it into appropriate clinical outcomes.SponsorshipYakult Honsha Co., Ltd.

Exploring the health-promoting potential: Dietary intervention with live or inactivated Lactobacillus gasseri HM1 probiotics in obese mice

BackgroundThis study explores the impact of dietary interventions with live or inactivated Lactobacillus gasseri HM1 probiotics on metabolic health in mice. MethodsAfter inducing obesity in 24 mice with a high-fat diet, they transitioned to a standard chow diet (SCD) while receiving a daily oral placebo, live HM1, heat-killed HM1 (HK-HM1), or sonication-killed HM1 (SK-HM1) for 6 weeks. ResultsResults indicate that SCD with live HM1 significantly improved triglyceride levels, glucose tolerance, and insulin sensitivity. SK-HM1 improved perirenal fat inflammation and reduced serum leptin concentration, while HK-HM1 showed improvements in inflammation in fat tissues and reduced serum IL-6, leptin, and catalase protein levels. Both HK-HM1 and SK-HM1 reduced colon IL-6, TGF-β1, and IL-1β cytokine levels, with HK-HM1 having the most significant effect. ConclusionsThese findings underscore the potential of dietary interventions with HM1 probiotics to enhance metabolic health, revealing distinct benefits between live and inactivated forms.

Effect of probiotics plus zinc supplementation on clinical outcomes of infants and children with acute infectious diarrhea: a randomized controlled trial.

Findings are conflicting regarding the effect of zinc supplementation on disease severity in children with acute gastroenteritis. To examine the effects of probiotics and zinc on the clinical outcomes of infants and children with acute infectious diarrhea. In this randomized controlled trial, children with mild or moderate to severe acute gastroenteritis in the Kurdistan Region from November 2021 to June 2022 were diagnosed clinically and randomly assigned to the experimental or control group. The experimental group (n=50) received probiotics and zinc, whereas the control group (n=51) received probiotics alone for 1 week. The product contained live Bifidobacterium infantis, Lactobacillus paracasei, and Lactobacillus rhamnosus (10×106 colony-forming units/day for 7 days). Zinc syrup was administered to the probiotic plus zinc group. Each 5 mL of syrup contained 15 mg of zinc sulfate. Dehydration and disease severity in both groups were measured using the Clinical Dehydration Scale and the Modified Vesikari Scale, respectively. An illness episode was defined as an episode of gastroenteritis with a total score of ≥9 on the Modified Vesikari Scale (range, 0-20). The probiotic and probiotic plus zinc groups were similar in age (1.79 years vs. 1.69 years, respectively; P= 0.645), sex (male/female ratio: 1.43 and 1.0, respectively; P=0.373), and medical characteristics. The groups had similar mean dehydration and disease severity scores and a similar incidence of dehydration recovery (some dehydration, 3.92% and 4.00%, respectively; P=1.000), and recovery from mild gastroenteritis (0.0% and 2.0%, respectively; P=0.495) at 2 weeks. Significant decreases in mean dehydration severity and disease severity score (1.80 to 0 and 6.66 to 0, respectively; P<0.001) and the development of dehydration (some dehydration, from 94.0% to 4.0%; P<0.001) from baseline to 2 weeks were noted in the probiotics plus zinc group. The probiotics group responded similarly. The development of mild gastroenteritis was significantly reduced from baseline to 2 weeks (90.2% to 0% and 78.0% to 2.0% in the probiotics and probiotics plus zinc groups, respectively; P<0.0001). The probiotics plus zinc group had a shorter mean recovery time (1.34 days vs. 2.00 days, respectively; P<0.001). Taking probiotics plus zinc did not significantly affect disease severity in children with gastroenteritis at 2 weeks. However, the probiotics plus zinc group recovered more quickly than the probiotics group.

Effects of Mesalamine Combined with Live Combined Bifidobacterium, Lactobacillus and Enterococcus Capsules on Intestinal Mucosa Barrier Function and Intestinal Microbiota in Mildly Active Crohn’s Disease Patients

Objective: This study is aimed at investigating the impact of mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules on intestinal mucosa barrier function and intestinal microbiota in mildly active Crohn’s disease patients. Methods: Ninety-six Crohn’s disease patients in mild activity period were randomized into the control group (treated with mesalamine) and the observation group (treated with mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules) (n = 48). After 4 wk of treatment, the patients were evaluated for their clinical efficacy. Intestinal microbiota counts, serum inflammatory factors, T lymphocyte subsets, and mucosal barrier function indicators in both groups were assessed. Results: After 4 wk of treatment, the total clinical effective rate of the observation group was higher than that of the control group. The number of Lactobacillus acidophilus (L. acidophilus) and Bifidobacterium Longum (B. longum) in the intestinal tract, serum IL-10 levels, and peripheral blood CD4+ and CD4+/CD8+ levels were higher, and the number of Bacteroides vulgatus (B. vulgatus), the levels of TNF-α, IL-6, CRP, CD8+, ET, D-lactate, DAO, and urine L/M ratio were lower in the observation group in comparison to those in the control group (all p < 0.05). Conclusion: Mesalamine combined with Live combined Bifidobacterium, Lactobacillus and Enterococcus capsules are more effective in treating mildly active Crohn’s disease.

Effect of transvaginal Lactobacillus supplementation on reversing lower genital tract dysbiosis and improving perinatal outcomes in PCOS patients after IVF-FET: a study protocol for a multicenter randomized controlled trial

BackgroundSignificant lower genital tract (LGT) dysbiosis and an associated lower rate of clinical pregnancy after in vitro fertilization–frozen embryo transfer (IVF-FET) among polycystic ovary syndrome (PCOS) patients have been previously reported by our group. We aimed to assess whether transvaginal Lactobacillus supplementation can reverse LGT dysbiosis and further improve perinatal outcomes in PCOS patients after IVF-FET.Methods/designThis is a protocol for a multicenter, open-label, randomized controlled trial in China. Women diagnosed with PCOS who are undergoing IVF-FET treatment will be recruited. Allocation to the intervention/control arms at a ratio of 1:1 will be executed by an electronic randomization system. Participants in the intervention arm will receive the live Lactobacillus capsule vaginally for 10 consecutive days before embryo transfer, while those in the control arm will receive standard individualized care. The primary outcomes will be the clinical pregnancy rate, implantation rate, and live birth rate. 16S rRNA sequencing and liquid chromatography–mass spectrometry will be conducted to evaluate the LGT microbiome and systemic metabonomics before and after the intervention. A sample of 260 participants will provide 95% power to detect a 20% increase in the rate of clinical pregnancy (α = 0.025, one-tailed test, 15% dropout rate). A total of 300 participants will be recruited.DiscussionThis is the first large and multicenter randomized controlled trial aimed at assessing the efficacy of transvaginal Lactobacillus supplementation on restoring the LGT microbiome and improving perinatal outcomes in PCOS patients after IVF-FET. This pragmatic trial is promising for increasing the rates of clinical pregnancy and live birth in PCOS patients after IVF-FET.Ethics and disseminationEthical review approval was obtained from the Medical Research Ethics Committees of the International Peace Maternity and Child Health Hospital of Shanghai Jiao Tong University (15 October 2020, GKLW 2020-29). To maximize dissemination, these findings will be reported in open access publications in journals with high impact, and oral and poster conference presentations will be performed.Trial registrationChiCTR ChiCTR2000036460. Registered on 13 September 2020, https://www.chictr.org.cn/showproj.html?proj=59549.

The effect of a microbiological product based on &lt;i&gt;Lactobacillus buchneri&lt;/i&gt; on barley growth and productivity in the Vologda region

The purpose of the work was to study the effect of the experimental microbiological product ‘Naturost-Aktiv’, developed on the basis of live bacteria Lactobacillus buchneri, on barley growth and productivity in the Vologda region. The study was carried out during the vegetation periods of 2019, 2020 and 2022 on the experimental field of the FSBIS «Vologda Research Center of the Russian Academy of Sciences», as well as in production conditions on the fields of the APC Collective farm «Peredovoy» (Vologda Region). The product ‘Naturost-Aktiv’ was applied twice, when the seeds of the experimental group were soaked in the working solution (1 ml of the product per 1 liter of water) and the phyllosphere of the plants was sprayed in the tillering phase. Tap water was used as control. As a result, there has been identified an increase in the potential energy supply of barley. The area of an individual leaf of experimental plants exceeded the control by 16 %, and the content of the total chlorophylls (a+b) exceeded by 34–42 %, which contributed to a more active accumulation of dry mass of experimental plants in comparison with the control (duringthe action of the product there was an increase in the dry weight of the plant by 12–65 % relative to the control). The changes in the plant growth processes also affected the grain productivity, which increased by 8–26 % in the variants with the product compared to the control. The results of the production experiment, in general, turned out to be like the results of small-plot experiments. Thus, in the conditions of real management, grain productivity of the barley variety ‘Sonet’ increased by 14 % with the use of the product ‘Naturost-Aktiv’ relative to the control. Grain productivity improvement was associated both with an increase in the number of productive shoots and with an increase in the weight of an individual grain.

ANALYSIS OF T-CELL IMMUNITY IN WOMEN WITH VAGINAL MICROBIOTA DISORDERS UNDER COMPLEX TREATMENT

Introduction. Immunological aspects of vaginal microbiota encompass the state of humoral and cellular immunity, which serves the primary function of nonspecific immune system stimulation. Therefore, alterations in its species composition lead to numerous disruptions in both cellular and humoral immune responses. The aim of the study – to investigate the parameters of T-cell immunity in women of reproductive age with vaginal microbiota disorders. Research Methods. We examined 115 women of reproductive age with vaginal microbiota disorders. To treat bacterial vaginosis in the third group of women according to the “Anomalous Vulvovaginal Discharge” treatment protocol, we selected the antibiotic metronidazole. In the second group with an intermediate type of vaginal microbiota, probiotics containing live Lactobacillus casei IMB B-7280 strains in the form of capsules and suppositories were used to normalize the species composition. After applying comprehensive therapy, we assessed the indicators of T-cell immunity in the study groups before treatment and one month after treatment. Results and Discussion. When studying T-cell immunity in women of reproductive age with vaginal microbiota disorders, no statistically significant changes in the levels of T-cells (CD3+, CD19-), T-helpers (CD4+, CD8-), and T-suppressors/T-cytotoxic cells (CD4-, CD8+) were found within the reference norms. However, statistically significant differences in T-suppressors/T-cytotoxic cells (CD4-, CD8+) were observed before treatment depending on the study groups. The lowest statistically significant level of these cells was found in the group of women with bacterial vaginosis, but the indicators of this immune branch tended to increase compared to the control group after complex treatment. After probiotic therapy, there was a tendency to increase T-helpers (CD4+, CD8-) in women with an intermediate type of vaginal microbiota. Conclusions. In conclusion, the analysis of the studied parameters of cellular immunity in women with vaginal microbiota disorders revealed a statistically significant decrease in T-suppressors/T-cytotoxic cells (CD4-, CD8+), which deepened as the vaginal microbiota disorder progressed. This indicates the influence of the species composition of vaginal microbiota on the T-suppressor/T-cytotoxic cellular immune branch.

Research on the development of composition and technology of an emulgel with a probiotic component for the treatment of infectious and inflammatory diseases

The aim was conducted research to develop the composition and technology of a new soft preparation under the conventional name "Probioskin" for topical use with a probiotic component in the form of an emulgel.&#x0D; Materials and methods of work. The homogeneity was determined by visual inspection of the experimental samples, using a biological microscope XSP-128 ULAB. The rheological (structural and mechanical) properties of the samples were studied using a Rheolab QC rheoviscosimeter (Anton Paar, Austria) with a C-CC27/SS coaxial cylinder system. The Rheolab QC rheometer is equipped with RheoPlus software. Microbiological studies and biotesting on a biological model of infusoria were performed under aseptic conditions of a laminar flow box (biological safety cabinet AC2-4E1 "Esco", Indonesia) of the Department of Biotechnology of the National University of Pharmacy. The identification of lactobacilli and the number of live cells as critical indicators of a preparation containing live microorganisms were performed at each stage of the study. Bacterioscopic control was carried out by examining smears prepared from samples of the dissolved drug and stained by Gram stain. Bacteriological control was performed by inoculation on thick MRS-4 medium and liquid MRS-1 medium. The number of live lactobacilli (when lactobacilli were co-cultured with the drug components at the stages of development and in the finished product) was determined by surface sowing on Petri dishes with thick MRS-4 medium; after 48 h of incubation at (37±1)°C, colonies grown on the surface of the medium were counted and the number of live lactobacilli expressed in CFU was calculated in 1 ml of the drug.&#x0D; Results and discussion. Based on the conducted research, the composition of a soft preparation for topical use containing dexpanthenol, lactic acid, lyophilized lactobacillus biomass, propylene glycol, peach oil, polysorbate-80, aristoflex AVC, tocopherol, and purified water was developed. The production process of the developed Probioskin product is carried out according to a standardized scheme and consists 8 stages: preparation of raw materials, preparation of oil concentrate of the probiotic component, preparation of aqueous concentrate of active substances, preparation of gel base, preparation of emulsion, dosing into tubes, packaging of tubes into packs, packaging of packs into group containers.&#x0D; Conclusions. On the basis of a complex research, the composition and rational technology of a soft preparation for topical use under the conventional name "Probioskin" in the form of an emulsion was developed.&#x0D; Key words: pharmacological research, soft drug, emulgel, probiotics, dermatological diseases

Ameliorative effect of Lactobacillus plantarum CCFM8661 on oleic acid-induced acne: Integrated the gut microbiota link to the acne pathogenesis.

Acne vulgaris is an inflammatory disease of the pilosebaceous unit of the skin that has serious adverse effects on the physical and mental health of patients. Probiotics are extensively employed in dermatology and could be an alternative option for acne therapy. Here, we evaluated the effect of oral ingestion of live and inactivated Lactobacillus plantarum CCFM8661 on oleic acid-induced acne using a mouse model. Results found that live L. plantarum CCFM8661 suppressed the skin inflammation and serum hormone (insulin and testosterone) production in acne mice. Parallelly, live L. plantarum CCFM8661 effectively reduced the formation of skin lipids (TG and NEFA), and normalized the expression of skin lipid metabolism-related genes (PPRA-γ, SREBP-1c, ACCα, FASN, PPRA-α, ACOX1, HSL and ATGL). In comparison, inactivated L. plantarum CCFM8661 had no effect on skin inflammation or serum hormone secretion, but decreased the skin TG and normalized the expression of skin lipid metabolism-related genes (PPRA-γ, SREBP-1c, FASN and ATGL) in acne mice. Both live and inactivated L. plantarum CCFM8661 raised the richness of gut microbiota, reduced the ratio of Bacteroidetes: Firmicutes, and decreased the relative abundance of Staphylococcus in the feces of acne mice. Oral ingestion of L. plantarum CCFM8661, particularly live cells, could alleviate acne by suppressing skin inflammation, normalizing the metabolism of hormones and skin lipids, which may be achieved by improving the gut microbial ecosystem. This article is protected by copyright. All rights reserved.

Orally administrated Lactobacillus gasseri TM13 and Lactobacillus crispatus LG55 can restore the vaginal health of patients recovering from bacterial vaginosis.

https://classic.clinicaltrials.gov/ct2/show/, identifier NCT04771728.

Rapid-dissolving electrospun nanofibers for intra-vaginal antibiotic or probiotic delivery

The emergence of probiotics as an alternative and adjunct to antibiotic treatment for microbiological disturbances of the female genitourinary system requires innovative delivery platforms for vaginal applications. This study developed a new, rapid-dissolving form using electrospun polyethylene oxide (PEO) fibers for delivery of antibiotic metronidazole or probiotic Lactobacillus acidophilus, and performed evaluation in vitro and in vivo. Fibers did not generate overt pathophysiology or encourage Gardnerella growth in a mouse vaginal colonization model, inducing no alterations in vaginal mucosa at 24 hr post-administration. PEO-fibers incorporating metronidazole (100 µg MET/mg polymer) effectively prevented and treated Gardnerella infections (∼3- and 2.5-log reduction, respectively, 24 hr post treatment) when administered vaginally. Incorporation of live Lactobacillus acidophilus (107 CFU/mL) demonstrated viable probiotic delivery in vitro by PEO and polyvinyl alcohol (PVA) fibers to inhibit Gardnerella (108 CFU/mL) in bacterial co-cultures (9.9- and 7.0-log reduction, respectively, 24 hr post-inoculation), and in the presence of vaginal epithelial cells (6.9- and 8.0-log reduction, respectively, 16 hr post-inoculation). Administration of Lactobacillus acidophilus in PEO-fibers achieved vaginal colonization in mice similar to colonization observed with free Lactobacillus. acidophilus. These experiments provide proof-of-concept for rapid-dissolving electrospun fibers as a successful platform for intra-vaginal antibiotic or probiotic delivery.

Chinese expert consensus on the application of live combined Bifidobacterium, Lactobacillus, and Enterococcus powder/capsule in digestive system diseases (2021).

Disturbance of gut microbiota is associated with pathological change in multiple diseases. Probiotics can improve symptoms and exert clinical effects via regulation of gastrointestinal microecological environments, and a probiotic product commonly dispensed by Chinese physicians is a combination of live Bifidobacterium, Lactobacillus, and Enterococcus in powder/capsule form. It contains three strains-of Bifidobacterium longum, Lactobacillus acidophilus, and Enterococcus faecalis-which can act synergistically to balance the microbiome, regulate immunity, and repair the gut barrier. Although this product has been proven safe and effective in clinical practice, uncertainty remains regarding its use to treat digestive system diseases. To date, there have been no reference standards to guide clinical practice and no relevant expert consensus on this product, in China. Following a literature search, evidence was graded and classified according to the grading of recommendations assessment, development, and evaluation (GRADE) system and consensus was secured from a panel of 52 experts. An expert consensus has been formed, on the clinical application of live combined Bifidobacterium, Lactobacillus, and Enterococcus in various digestive system diseases, to provide reference for its clinical use. Bifidobacterium triple viable powder/capsule may offer benefits, by regulating the balance of intestinal microecology. It can be used for the treatment and prevention of various digestive system diseases with good overall safety; further research is needed to confirm its application in other contexts. The recommendations in this consensus will be confirmed or refined in light of future research and clinical practice.

Abstract P1-12-11: Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer

Abstract Objective: Pyrotinib, an oral irreversible pan-HER receptor tyrosine kinase inhibitor, showed promising efficacy and manageable safety profiles in the treatment of HER-2 positive breast cancer. Diarrhea is the most common adverse event associated with pyrotinib. This study aimed to evaluate the incidence and management of diarrhea secondary to pyrotinib in Chinese patients with HER-2 positive breast cancer. Methods: In this prospective real-world study, consecutive patients aged over 18 with HER-2 positive breast cancer and an Eastern Cooperative Oncology Group performance status (ECOG PS) of 0-2 who planned to receive pyrotinib-based regimens for at least 21 days were included. Pyrotinib-treated patients and those with preexisting gastrointestinal conditions were excluded. There were no planned management strategy or primary prophylaxis for diarrhea, while loperamide, montmorillonite powder or Golden Bifid (a live combined Bifidobacterium, Lactobacillus and Streptococcus Thermophilus tablet) were recommended. Treatment was given in accordance with routine clinical practice by investigators. For patients developed grade 3 or higher diarrhea, pyrotinib was suspended until the diarrhea improving to grade 1 or less, and secondary prophylaxis (such as loperamide, loperamide plus montmorillonite powder, or loperamide plus Golden Bifid) was administrated before pyrotinib resumption. The baseline characteristics of patients and details of diarrhea (onset time, duration, severity according to the National Cancer Institute-Common Terminology Criteria for Adverse Events version 4.03, treatment and prognosis) were collected. Results: Between August, 2020 and April, 2022, a total of 107 eligible patients were included, with a median age of 54 (range: 25-81) years old. Most patients (93.5%) had an ECOG PS of 0-1, and 51 patients (47.7%) were hormone receptor positive. A total of 46 patients (43.0%) received pyrotinib in the early stage and 61 (57.0%) in the advanced stage. Sixty-nine cases (64.5%) used pyrotinib-containing combination therapy (including 40 combined with capecitabine, 13 combined with trastuzumab, and 16 combined with other regimens), and 38 (35.5%) received pyrotinib alone. Ninety-eight cases (91.6%) reported diarrhea of any grade. Grade 1, 2 and 3 diarrhea occurred in 78 (72.9%), 9 (8.4%) and 11 (10.3%) patients, respectively. The median time to first onset of diarrhea of any grade was 2.5 (1-12) days, and the duration of first onset was 4 (1-24) days. The cumulative duration of diarrhea was 10 (1-60) days. Sixty-four, two, thirty, two patients used loperamide alone, montmorillonite powder alone, loperamide plus montmorillonite powder and loperamide plus Golden Bifid for the treatment of diarrhea, respectively. Eleven (10.3%) and seven (6.5%) patients experienced pyrotinib dose reduction and pyrotinib discontinuation. For 11 patients suffered grade 3 diarrhea, the median time to first onset of grade 3 diarrhea was 9 (4-14) days. Two, four and five patients administrated loperamide, loperamide plus Golden Bifid and loperamide plus montmorillonite powder as their secondary prophylaxis. Ten of eleven had grade 1 or 2 diarrhea after secondary prophylaxis, while one patient still suffered grade 3 diarrhea. All of them (11/11) held the pyrotinib dose. The incidence rate of constipation of all patients was 3.7%, which did not increase after treatment or secondary prophylaxis for diarrhea. Conclusion: In this study, the majority of patients developed pyrotinib associated diarrhea, and most of them were grade 1. About 10% patients reported grade 3 diarrhea, which can be managed by loperamide-based treatment and secondary prophylaxis. Table 1. Baseline characteristics of patients ECOG PS: Eastern Cooperative Oncology Group performance status; HER-2: human epidermal growth factor receptor 2. Table 2. Summary of patients developed diarrhea Table 3. Summary of patients developed grade 3 diarrhea Citation Format: Hong Liu, Li Ma, Xu Wang, Xinzhong Chang, Qi Yu, Qingfeng Huang, Chunfang Hao, Jun Liu, Jing Zhao, Shufen Li, Zhongsheng Tong, Yehui Shi, Ning Lu, Weipeng Zhao, Tong Wang, Xuchen Cao, Chen Wang, Juntian Liu, Ying Zhao, Lina Zhang, Baoliang Guo, Xin Wang, Xu Di, Chunhui Gao, Zongzhan Liu, Shuo Sun, Linwei Li. Real-world incidence and management of diarrhea secondary to pyrotinib in patients with HER-2 positive breast cancer [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-12-11.

Lactobacilli and Their Probiotic Effects in the Vagina of Reproductive Age Women.

In the present narrative review, the probiotic effects of vaginal Lactobacillus spp. are described in detail, covering the importance of the differential production of lactic acid, the lactic acid D/L isoforms, the questionable in vivo effect of hydrogen peroxide, as well as bacteriocins and other core proteins produced by vaginal Lactobacillus spp. Moreover, the microbe-host interaction is explained with emphasis on the vaginal mucosa. To understand the crucial role of Lactobacillus spp. dominance in the vaginal microbiota, different dysbiotic states of the vagina are explained including bacterial vaginosis and aerobic vaginitis. Finally, this review takes on the therapeutic aspect of live lactobacilli in the context of bacterial vaginosis. Until recently, there was very low-quality evidence to suggest that any probiotic might aid in reducing vaginal infections or dysbiosis. Therefore, clinical usage or over the counter usage of probiotics was not recommended. However, recent progress has been made, moving from probiotics that are typically regulated as food supplements to so-called live biotherapeutic products that are regulated as medical drugs. Thus, recently, a phase 2b trial using a Lactobacillus crispatus strain as a therapeutic add-on to standard metronidazole showed significant reduction in the recurrence of bacterial vaginosis by 12 weeks compared to placebo. This may constitute evidence for a brighter future where the therapeutic use of lactobacilli can be harnessed to improve women's health.

Effects of Combined Live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus Cereus Tablets on Post-Stroke Depression and Serum Inflammatory Factorse.

Although probiotics have been shown to improve several mental-related diseases, their association with post-stroke depression (PSD) remains unclear. This research aimed to investigate the effect of combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets on PSD and serum inflammatory factors. A total of 400 stroke patients treated from January 2020 to March 2022 in Shuyang Hospital were included and randomly divided into two groups: The observation group (n = 200) and the control group (n = 200). The control group was treated with conventional therapy, while the observation group was given combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets on the basis of conventional therapy. The Hamilton Depression Scale score was used to assess the degree and incidence of depression in the two groups. Recurrence and complications of PSD in stroke patients after treatment were followed up. In addition, ELISA (enzyme-linked immunosorbent assay) was employed for the detection of serum levels of nuclear factor kappa light chain enhancer of activated B cells (NF-κB), interleukin (IL)-1β and tumor necrosis factor (TNF)-α, and logistics regression analysis was also performed for the correlation between the occurrence of PSD and NF-κB, IL-1β, and TNF-α levels. The analysis of clinical baseline data showed that the two groups of patients were comparable. After treatment, the Hamilton Depression Scale score in the observation group was significantly lower than in the control group (p < 0.05), and the observation group had a lower incidence rate of PSD, follow-up recurrence rate and complications (p < 0.05). In addition, the observation group showed a significant decrease in the serum levels of NF-κB, IL-1β and TNF-α compared with the control group (p < 0.05). Further logistics regression analysis indicated that the levels of NF-κB (OR (odds ratio) = 3.337, p < 0.001), IL-1β (OR = 2.411, p < 0.001) and TNF-α (OR = 1.557, p < 0.001) were risk factors for the development of PSD. Combined live Bifidobacterium, Lactobacillus, Enterococcus and Bacillus cereus tablets can promote neurological recovery and remission of depression in stroke patients. Such effects may be achieved by regulating the levels of NF-κB, IL-1β and TNF-α.

Optimizing the vaginal microbiome as a potential strategy to reduce heterosexual HIV transmission.

Bacterial vaginosis (BV) is a proinflammatory genital condition characterized by high vaginal bacterial diversity and a paucity of Lactobacillus species. BV has been linked to an elevated risk of HIV acquisition among HIV-negative women and of forward HIV transmission to male sex partners among women living with HIV (adjusted hazard ratios of 1.69 and 3.17, respectively), potentially by eliciting genital inflammation in women with BV and their male sex partners. BV is also highly prevalent among women in sub-Saharan Africa, suggesting that BV treatment may have potential as an HIV prevention strategy. BV is typically treated with antibiotics but recurrence rates are high, possibly because treatment does not directly promote Lactobacillus growth. More recently, BV treatment strategies incorporating live biotherapeutic lactobacilli have led to sustained optimization of the vaginal microbiome and a decrease in inflammatory biomarkers previously associated with HIV susceptibility. Future studies are urgently needed to evaluate BV treatment strategies that can optimize the vaginal microbiome in the long term through colonization with H2 O2 -producing vaginal lactobacilli and to assess whether vaginal microbiota optimization is able to reduce the risk of HIV transmission.