-
Cell Host & Microbe May 2023Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver...
Acetaminophen (APAP) overdose is a leading cause of drug-induced liver injury (DILI). The impact of the gut microbiota and associated metabolites on APAP and liver function remains unclear. We show that APAP disturbance is associated with a distinct gut microbial community, with notable decreases in Lactobacillus vaginalis. Mice receiving L. vaginalis showed resistance to APAP hepatotoxicity due to the liberation of the isoflavone daidzein from the diet by bacterial β-galactosidase. The hepatoprotective effects of L. vaginalis in APAP-exposed germ-free mice were abolished with a β-galactosidase inhibitor. Similarly, β-galactosidase-deficient L. vaginalis produced poorer outcomes in APAP-treated mice than the wild-type strain, but these differences were overcome with daidzein administration. Mechanistically, daidzein prevented ferroptotic death, which was linked to decreased expression of farnesyl diphosphate synthase (Fdps) that activated a key ferroptosis pathway involving AKT-GSK3β-Nrf2. Thus, liberation of daidzein by L. vaginalis β-galactosidase inhibits Fdps-mediated hepatocyte ferroptosis, providing promising therapeutic approaches for DILI.
Topics: Animals; Mice; Acetaminophen; beta-Galactosidase; Chemical and Drug Induced Liver Injury; Gastrointestinal Microbiome; Isoflavones; Liver; Mice, Inbred C57BL; NF-E2-Related Factor 2
PubMed: 37100057
DOI: 10.1016/j.chom.2023.04.002 -
Annals of Palliative Medicine Jan 2022To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, β-catenin,...
BACKGROUND
To detect the correlation between Lactobacillus vaginalis and the expression of epithelial-mesenchymal transition (EMT)-related factors, E-cadherin, β-catenin, N-cadherin, and Vimentin, in postmenopausal cervical squamous intraepithelial lesions (SILs) and cervical squamous cell carcinoma (SCC), and to explore the possible mechanism.
METHODS
From January 2016 to January 2020, 30 postmenopausal patients with low-grade SIL (LSIL), 18 patients with high-grade SIL (HSIL), and 30 patients with SCC who underwent colposcopy biopsy in the Outpatient Department of the First Affiliated Hospital of Inner Mongolia Medical University were selected as the experimental group, and 30 postmenopausal normal women were selected as the control group. The expression of 16SrRNA of Lactobacillus vaginalis in each group was determined by the 16S third-generation full-length amplification sequencing technique. The mRNA expression levels of E-cadherin, β-catenin, N-cadherin, and Vimentin were detected by quantitative real-time polymerase chain reaction (qPCR). The correlation between the 16SrRNA expression level of Lactobacillus vaginalis and the mRNA expression level of the EMT-related proteins was compared among all groups.
RESULTS
(I) The progression of postmenopausal cervical SILs to cervical SCC was significantly positively correlated with age, number of pregnancies, smoking, pH value, positive rate of HPV16, and negatively correlated with total Lactobacillus 16SrRNA expression (P<0.0001). (II) The level of vaginal microbiota in postmenopausal women showed that Lactobacillus iners was dominant. With the progression of the disease, the expression levels of 16SrRNA in Lactobacillus iners and Lactobacillus total vagina decreased gradually, and the differences were statistically significant (P<0.05). (III) With the disease progresses. The expression of total Lactobacillus 16SrRNA was positively correlated with the mRNA expression of β-catenin and E-cadherin (r>0; P<0.05), and negatively correlated with the mRNA expression of Vimentin and N-cadherin (r<0; P<0.05).
CONCLUSIONS
In postmenopausal women, Lactobacillus vaginalis interacts with HPV and is associated with the occurrence of EMT, promoting the development of cervical lesions.
Topics: Alphapapillomavirus; Cadherins; Epithelial-Mesenchymal Transition; Female; Humans; Lactobacillus; Postmenopause; Pregnancy; Uterine Cervical Diseases; Vimentin; beta Catenin
PubMed: 35144405
DOI: 10.21037/apm-21-3581 -
Frontiers in Microbiology 2021Lactobacilli are the dominant members of the healthy human vaginal microbiota and represent the first defense line from pathogen infection, including vulvovaginal...
Lactobacilli are the dominant members of the healthy human vaginal microbiota and represent the first defense line from pathogen infection, including vulvovaginal candidiasis. Biofilm is the predominant microbial growth form in nature, and the formation of biofilms inside the human body has important implications in health and disease. In particular, the formation of biofilm by members of the human resident microbiota is desirable, as it can improve microbial persistence and influence functionality. In the present study, we investigated the capability of 16 vaginal strains (belonging to , , and species) to form biofilms, and we correlated their mode of growth to anti- activity. strains were the best biofilm producers, and high variability was registered in the level of biofilm formation among and strains. Culture supernatants derived from biofilm and planktonic growth were tested toward a panel of clinical isolates (, , , and ) and their metabolome assessed by H-NMR. and strains exhibited the best fungistatic profile, and biofilms enhanced their anti- activity; on the contrary, strains were more effective when grown in a planktonic mode. Biofilm/planktonic mode of growth also affects metabolism, mainly influencing nitrogen and amino acid pathways, and anti- activity is instead strictly related to carbohydrate metabolism. The present study underlined the strict interdependence between microbial mode of growth, metabolism, and functional properties. Biofilm formation by members of the healthy human microbiota represents a crucial issue in the field of microbial physiology and host-microbiota interactions, beyond supporting the development of new antimycotic strategies based on probiotics grown in adherence.
PubMed: 34777300
DOI: 10.3389/fmicb.2021.750368 -
Frontiers in Immunology 2022Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but...
Food allergy is a serious public health problem because of its high incidence and risk. Probiotics can induce immune regulation in patients with allergic diseases, but its mechanism is not fully clear. In this paper, β-lactoglobulin (β-LG)-sensitized mice were used as models to explore the mechanism of KV9 (KV9) and FN3 (FN3) on reducing allergic reactions and regulating immune cell function. The results showed that oral administration of KV9 and FN3 significantly reduced the scores of allergic symptoms, hypothermia symptoms, and serum levels of β-LG-specific immunoglobulins E (β-LG-sIgE), histamine, and mast cell protease in allergic mice. Flow cytometry analysis of intestinal dendritic cells (DCs) showed that the proportion of CD11c+major histocompatibility complex (MHC)-II+DCs, CD11c+CD80+DCs, and CD11c+ CD86+DCs increased after KV9 and FN3 intervention, indicating that the strains induced immature DCs and decreased the antigen-presenting capacity of DCs. Meanwhile, the toll-like receptor 4 (TLR4)-NF-κB signaling pathway was activated in DCs. The secretion of interleukin-12 (IL-12) was significantly increased, while interleukin-4 (IL-4) was decreased by DCs after KV9 and FN3 intervention, indicating that DCs have the potential to promote T-cell differentiation into T helper type 1 (Th1) cells. Furthermore, the proportion of CD3+CD8-IFN-γ+ T cells in the spleen increased, while CD3+CD8-IL-4+T cells decreased after oral administration of KV9 and FN3, correcting the T helper type 2 (Th2)-skewed immune responses. These results indicate that KV9 and FN3 reduce β-LG-induced allergic symptoms in mice, and suggest that the two potential probiotics might be used as an alternative therapeutic agent for mitigating food allergy.
Topics: Animals; Bifidobacterium animalis; Dendritic Cells; Food Hypersensitivity; Histamine; Immunoglobulin E; Interleukin-12; Interleukin-4; Lactobacillus; Lactoglobulins; Mice; NF-kappa B; Peptide Hydrolases; Toll-Like Receptor 4
PubMed: 36238281
DOI: 10.3389/fimmu.2022.992605 -
NPJ Biofilms and Microbiomes Aug 2023Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal...
Inflammatory bowel disease (IBD) is associated with gut dysbiosis and can lead to colitis-associated malignancies. Bacteroides uniformis (Bu) regulates animal intestinal homeostasis; however, the mechanism by which it alleviates colitis in mice remains unknown. We investigated the effects of B. uniformis JCM5828 and its metabolites on female C57BL/6J mice with dextran sulfate sodium salt (DSS) induced colitis. Treatment with Bu considerably alleviated colitis progression and restored the mechanical and immune barrier protein expression. Additionally, Bu increased the abundance of the symbiotic bacteria Bifidobacterium and Lactobacillus vaginalis while decreasing that of pathogenic Escherichia-Shigella, and modulated intestinal bile acid metabolism. Bu largely regulated the expression of key regulatory proteins of the NF-κB and mitogen-activated protein kinase (MAPK) signaling pathways in colonic tissues and the differentiation of TH17 cells. However, Bu could not directly inhibit TH17 cell differentiation in vitro; it modulated the process in the lamina propria by participating in bile acid metabolism and regulating key metabolites (alpha-muricholic, hyodeoxycholic, and isolithocholic acid), thereby modulating the intestinal immune response. Our findings suggest that Bu or bile acid supplements are potential therapies for colitis and other diseases associated with intestinal barrier dysfunction.
Topics: Female; Mice; Animals; Th17 Cells; Bile Acids and Salts; Gastrointestinal Microbiome; Mice, Inbred C57BL; Colitis; Microbiota; Cell Differentiation; Dextran Sulfate
PubMed: 37580334
DOI: 10.1038/s41522-023-00420-5 -
Microbiology Spectrum Feb 2023The gut of babies born vaginally is rapidly colonized by spp. after birth, while in infants born by cesarean section (C-section), the presence of bifidobacteria drops...
The gut of babies born vaginally is rapidly colonized by spp. after birth, while in infants born by cesarean section (C-section), the presence of bifidobacteria drops dramatically, increasing the risk of developing gastrointestinal disorders. Considering that newborns naturally come into contact with maternal lactobacilli as they pass through the birth canal, the aim of this work is to exploit for the first time the bifidogenic activity exerted by the cell-free supernatants (CFSs) from lactobacilli of vaginal origin, belonging to the species Lactobacillus crispatus, Lactobacillus gasseri, Limosilactobacillus vaginalis, and Lactiplantibacillus plantarum. CFSs were recovered after 7 h, 13 h, and 24 h of fermentation and assessed for the ability to stimulate the planktonic growth and biofilms of strains belonging to species widely represented in the gut tract. A bifidogenic effect was observed for all CFSs; such activity was maximal for CFSs recovered in exponential phase and was strongly dependent on the species of lactobacilli. Importantly, no stimulating effects on an intestinal Escherichia coli strain were observed. CFSs from L. vaginalis BC17 showed the best bifidogenic profile since they increased bifidobacterial planktonic growth by up to 432% and biofilm formation by up to 289%. The CFS at 7 h from BC17 was successfully formulated with a hyaluronic acid-based hydrogel aimed at preventing and treating breast sores in lactating women and exerting bifidogenic activity in infants born mainly by C-section. Bifidobacteria in the gut tract of infants play crucial roles in the prevention of gastrointestinal diseases and the maturation of the immune system. Consequently, strategies to trigger a bifidogenic shift in the infant gut are highly desirable. Evidences suggest that the presence of a maternal vaginal microbiota dominated by health-promoting lactobacilli and the development of a bifidobacterium-enriched gut microbiota in newborns are interconnected. In this context, we found out that the cell-free supernatants from lactobacilli of vaginal origin were able to effectively stimulate the proliferation of spp. grown in free-floating and biofilm forms. The cell-free supernatant from BC17 showed excellent bifidogenic behavior, which was preserved even after its incorporation into a nipple formulation for lactating women. Lactobacilli derivatives, such as cell-free supernatants, have gained increasing interest by virtue of their safer profile than that of living cells and can be proposed as an ecosustainable approach to favor gut colonization of infants by bifidobacteria.
Topics: Infant; Humans; Infant, Newborn; Female; Pregnancy; Cesarean Section; Bifidobacterium; Lactation; Lactobacillus
PubMed: 36602371
DOI: 10.1128/spectrum.02009-22 -
Zhong Nan Da Xue Xue Bao. Yi Xue Ban =... Nov 2022Pelvic floor dysfunction (PFD) seriously affects women's physical and mental health. Pregnancy and childbirth are recognized as high-risk factors for PFD, and studies...
OBJECTIVES
Pelvic floor dysfunction (PFD) seriously affects women's physical and mental health. Pregnancy and childbirth are recognized as high-risk factors for PFD, and studies have shown that vaginal microenvironmental disorders can promote the development of pelvic organ prolapse. In this study, we intend to investigate whether the changes in vaginal microecology during pregnancy affect the pelvic floor function and participate in the development of postpartum PFD, and provide a basis for the prevention and treatment of PFD.
METHODS
A total of 358 full-term mothers who delivered in Third Xiangya Hospital, Central South University from November 2019 to April 2020 were selected and underwent review 6 to 8 weeks after delivery. The pelvic floor structures were examined using pelvic floor ultrasound, and ultrasound values were measured at rest and at maximum Valsalva maneuver. One hundred and seventy women with PFD were assigned in a PFD group, and 188 women without PFD were assigned in a control group. The clinical data of all mothers were collected, and the clinical data and the results of microecological testing for vaginal secretions after 36 weeks of gestation and before delivery were compared between the 2 groups. The correlation of PFD with leucorrhoea cleanliness, lactobacillus level, bacterial vaginosis (BV), and vulvovaginal candidiasis (VVC) was analyzed, and logistic regression analysis was used to screen for independent risk factors for PFD.
RESULTS
The incidences of VVC, BV, Lactobacillus vaginalis deficiency, and leucorrhoea cleanliness ≥III° were all higher in the PFD group than those in the control group (P<0.05). Among them, leukocyte cleanliness ≥III°and lack of Lactobacilli in the vagina were independent risk factors for the development of PFD, while VVC and BV were not independent risk factors for the development of PFD.
CONCLUSIONS
Postpartum PFD is related to vaginal microecological imbalance in late pregnancy, among which Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° are independent risk factors for the occurrence of PFD. Therefore, pregnant women with Lactobacillus vaginalis deficiency and leucorrhoea cleanliness ≥III° in late pregnancy should pay attention to the occurrence of postpartum PFD, and early diagnosis and effective intervention of postpartum PFD should be enhanced.
Topics: Pregnancy; Female; Humans; Pelvic Floor; Mothers
PubMed: 36481640
DOI: 10.11817/j.issn.1672-7347.2022.220100 -
Journal of Traditional and... Mar 2023Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study...
BACKGROUND AND AIM
Dachengqi Decoction (DCQD) as a classic traditional Chinese medicine has been reported to be effective in treating asthma, but its mechanism remains unknown. This study aimed to reveal the mechanisms of DCQD on the intestinal complications of asthma mediated by group 2 innate lymphoid cells (ILC2) and intestinal microbiota.
EXPERIMENTAL PROCEDURE
Ovalbumin (OVA) was used to construct asthmatic murine models. IgE, cytokines (e.g., IL-4, IL-5), fecal water content, colonic length, histopathologic appearance, and gut microbiota were evaluated in asthmatic mice treated with DCQD. Finally, we administered DCQD to antibiotic-treated asthmatic mice to measure the ILC2 in the small intestine and colon.
RESULTS AND CONCLUSION
DCQD decreased pulmonary IgE, IL-4, and IL-5 levels in asthmatic mice. The fecal water content, the colonic length weight loss, and the epithelial damage of jejunum, ileum, and colon of asthmatic mice were ameliorated by DCQD. Meanwhile, DCQD greatly improved intestinal dysbiosis by enriching , and in the whole intestine, and only in the colon. However, DCQD caused less abundant and in the small intestine of asthmatic mice. A higher ILC2 proportion in different gut segments of asthmatic mice was reversed by DCQD. Finally, significant correlations appeared between DCQD-mediated specific bacteria and cytokines (e.g., IL-4, IL-5) or ILC2. These findings indicate that DCQD alleviated the concurrent intestinal inflammation in OVA-induced asthma by decreasing the excessive accumulation of intestinal ILC2 in a microbiota-dependent manner across different gut locations.
PubMed: 36970460
DOI: 10.1016/j.jtcme.2023.01.003 -
MBio Aug 2022It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to...
It is important to understand the microbial features of the cerebral thrombus and its clinical relevance in stroke patients, of which data were scarce. We aimed to investigate the microbial features of cerebral thrombi retrieved via thrombectomy in stroke patients with large vessel occlusion (LVO) and their correlations with 3-month mortality. In a prospective cohort study, thrombus samples were collected during mechanical thrombectomy in LVO stroke patients with successful revascularization at a tertiary hospital. Oral, fecal, and isolated plasma samples were collected within 12 h of admission. The microbial compositions of all samples were compared using 16S rRNA gene amplicon next-generation sequencing. Fluorescent hybridization (FISH) was used to detect bacteria in thrombus samples. The primary outcome was 3-month mortality. Perioperative adverse events (AEs) within 48 h were also recorded. Bacterial DNA was detected in 96.2% of thrombus samples from 104 patients, and clusters of bacterial signals were seen in the thrombi with FISH. Compared with fecal and oral samples, the thrombus microbiota was mainly characterized by excessive enrichment of , mainly originating from plasma. The bacterial concentrations, dominant bacteria, and distribution patterns differed in thrombi obtained from cardioembolic and large-artery atherosclerotic strokes. Higher abundances of Acinetobacter and were associated with a higher risk of perioperative AEs, and a higher abundance of Acinetobacter was independently associated with a higher risk of 90-day mortality. This study demonstrated the presence of bacteria in cerebral thrombi retrieved with thrombectomy in LVO strokes, with some bacteria associated with patients' prognoses. In this study, we (i) checked for the presence of bacteria in cerebral thrombi in over 95% of the LVO stroke patients using 16S rRNA sequencing, in contrast with periprocedural control samples that are bacteria negative; (ii) visualized clusters of bacterial signals in the thrombi using FISH; and (iii) cultivated Lactobacillus vaginalis, Bacillus cereus, and Kocuria marina in the bacterial culture of the tissue fragment solution of thrombus aspirates. We found excessive enrichment of in the thrombi, mainly originating from plasma, as indicated with fast expectation-maximization microbial source tracking (FEAST). Different bacterial concentrations, dominant bacteria, and distribution patterns were found in thrombi obtained from cardioembolic and large-artery atherosclerotic LVO strokes. There was an association between higher abundances of Acinetobacter and in the thrombi and a higher risk of perioperative adverse events and an association between a higher abundance of Acinetobacter in the thrombi and a higher risk of 90-day mortality.
Topics: Atherosclerosis; Bacteria; Brain Ischemia; Humans; In Situ Hybridization, Fluorescence; Intracranial Thrombosis; Prospective Studies; RNA, Ribosomal, 16S; Retrospective Studies; Stroke; Thrombosis
PubMed: 35726919
DOI: 10.1128/mbio.01085-22 -
Microorganisms Apr 2021The main aim of this work was to verify the metabolic and functional aptitude of 15 vaginal strains belonging to , , and (previously ), already characterized for their...
The main aim of this work was to verify the metabolic and functional aptitude of 15 vaginal strains belonging to , , and (previously ), already characterized for their technological and antimicrobial properties. In order to evaluate the metabolic profile of these vaginal strains, a phenotype microarray analysis was performed on them. Functional parameters such as hydrophobicity, auto-aggregation, deconjugation of bile salts, adhesion to an intestinal cell line (Caco-2), and a simulated digestion process were evaluated for these strains. A good number of these strains showed hydrophobicity values higher than 70%. Regarding the auto-aggregation assay, the most promising strains were BC9 and BC1, BC10 and BC14, and BC17. Moreover, BC4, BC6, BC7, and BC8 were characterized by strong bile salts hydrolase activity (BHS). In addition, BC8 and BC17 were characterized by a medium ability to adhere to Caco-2 cells. Data related to digestion process showed a strong ability of vaginal lactobacilli to withstand this stress. In conclusion, the data collected show the metabolic versatility and several exploitable functional properties of the investigated vaginal lactobacilli.
PubMed: 33919838
DOI: 10.3390/microorganisms9040833