Shili Liu

Alterations in the vaginal microbiota contribute to the pathogenesis of cervical neoplasia. However, the distinctions in microbiota changes related to different human papillomavirus (HPV) subtypes, as well as the variation in gut microbiota, have not been fully explored. In this research, we endeavored to explore the shifts in the vaginal and intestinal microbiota in correlation with the advancement of cervical neoplasia and HPV infection. A total of 578 vaginal and intestinal cross-sectional specimens were collected from 348 subjects and subjected to 16 S rRNA sequencing. Statistical analyses were performed using R language, and Student’s t-test was employed to assess the significance of differences. Both within and between, sample diversity of the vaginal and intestinal microbiota exhibited substantial alterations across cervical intraepithelial neoplasia (CIN) stages and cervical carcinoma. The vaginal genera Lactobacillus, Enterococcus, Peptoniphilus, Atobium, Anerococcus, and Veillonella were associated with different CIN stages and cervical cancer type, whereas Allisonella, Lachnospiracae, Lactobacillus, Staphylococcus, and Sellimonas were associated with varying HPV types. A Random Forest-driven classifier highlighted the predictive potential of differential bacteria in cervical neoplasia and HPV infection, with intestinal bacteria showing higher predictive accuracy in certain instances. Specifically, the accuracy of differentiating CIN I from CIN III was superior for the intestinal bacterial model compared to the vaginal bacterial model (85.52% vs. 83.33%). The model also demonstrated high accuracy in predicting HPV infection, particularly in distinguishing HPV-16 from HPV-18 and HPV-58, with AUC values of 81.61% and 83.07%, respectively, compared to less than 70% for vaginal bacteria. Our findings reveal the intricate interplay among cervical neoplasia, HPV infection, and microbiota, with potential diagnostic and therapeutic implications.

The microbiome present throughout the human body serves a variety of functions. In this study, 16S rRNA sequencing is employed to uncover differences in the abundance of Lactobacillus within the vaginal microbiota between individuals with cervical cancer and those with healthy cervixes. The research further identifies that the metabolite of Lactobacillus crispatus can induce ferroptosis in cervical cancer cells. This conclusion is reached through targeted bacterial culture, patient‐derived organoids (PDO) and single‐cell RNA sequencing. Erucic acid, identified as a primary metabolite via untargeted metabolomics, acts as a ligand for PPARδ receptor. It has the capacity to activate PPARδ pathway and subsequently trigger downstream fatty acid oxidation (FAO). Excessive enhancement of FAO can generate large amounts of H ₂ O ₂ and O ₂ ‐, known as ROS. Utilizing PDO, cell lines and cervical cancer xenograft (CDX) models, the study demonstrate both in vitro and in vivo that the metabolite of L. crispatus , erucic acid, can modulate the proliferation, migration and invasion of cervical cancer by activating the PPAR‐δ pathway. This activation leads to fatty acid oxidation, release ROS, and ultimately induces ferroptosis. Therefore, L. crispatus and erucic acid show potential as novel adjuvant therapeutic agents in the treatment of cervical cancer.

Fermentation of cigar tobacco leaves involves intense microbial activity, and hence, microorganisms have a significant impact on the quality and flavour of cigars. However, research on the correlation between microbial communities and the sensory quality of cigars remains inconclusive. In this study, a comparative analysis of the microbial profiles of five Caribbean- and five Chinese-produced cigar products was conducted to reveal significant differences in the microbiome of cigars from two origins, potentially accounting for the variance in their quality and flavour. Our findings indicated that Chinese cigars supported a more diverse array of microorganisms compared to Caribbean counterparts, as evidenced by higher indices of α and β diversity. High-throughput sequencing revealed that the genus Staphylococcus was predominant in Caribbean cigars, representing over half of the bacterial population. In contrast, Staphylococcus comprised approximately 30% of the bacterial community in most Chinese cigar samples. Furthermore, a clear distinction of function prediction between Caribbean and Chinese cigars implied chemical biotransformation of cigar tobacco leaves under the influence of microbial communities. Subsequent comprehensive statistical analysis of the correlation between the microbiome and sensory quality of cigars suggested that certain bacterial species may be critical in shaping the flavour profile of cigars. Together, these insights indicated that the core microbiome of Caribbean and Chinese cigars was different, with each product exhibiting its characteristic bacterial genera. The unique genera presented in the core microbiome of Caribbean cigars could provide a novel perspective on the bioaugmentation fermentation of Chinese cigars.

BACKGROUND: The microbiota has been reported to play an important role in the occurrence of brain aneurysms (CA). However, no microbiota or metabolite has been used for diagnosis or therapy of CA till now. Therefore, we investigated the shifts of gut microbiota and metabolites in CA patients, and explored the feasibility of using them as biomarkers and therapeutic targets. METHODS: The microbial DNA was extracted from the stool samples of the CA and healthy volunteer groups. The variable V3-V4 region of the 16S rDNA gene was sequenced on a MiSeq system. R software package was used to analyze the sequence, and the variations in microbial composition was obtained. The correlation analysis of the differential intestinal bacteria, metabolites and blood parameters was explored based on a logistic regression model. A random forest algorithm was used to predict the classification of samples for further exploring the relationship between fecal microbiota and CA. RESULTS: The α-diversity indexes demonstrated an altered within-sample microbial diversities between patients and healthy people. The subsequent beta diversity results indicated that shift in the between-sample microbial diversities of the intestinal microbiota was associated with the occurrence of cerebral aneurysm. Specifically, the abundance of some gut bacterial genera, such as Blautia and Faecalibacterium, changed significantly after CA. Intestinal metabolite enrichment results highlight the role of carbohydrate metabolic pathways in CA, including sedoheptulose 7-phosphate (S-7-P). The correlation analysis of the differential intestinal bacteria, metabolites and blood parameters indicated that intestinal bacteria and metabolites were related to host blood parameters. Then, the predictive models were employed to test the significance of the combination of differential bacteria, metabolites and blood parameters in CA diagnosis and prognosis. The predictive model built by Faecalibacterium and s7p obtained an area under ROC curve (AUC) of 99.7%, and Faecalibacterium and s-7-p were also associated with some metabolite that have significance in post-surgery prognosis of CA. Conclusions: The gut microbiota and metabolites profiles of patients with CA were significantly altered. Bacterial genus Faecalibacterium and metabolite s-7-p could serve as potential biomarkers in CA prediction and post-surgery prognosis.

Background Identification of the risk factors for atrophic gastritis (AG) and prevention of further deterioration of the gastritis are effective approaches to reduce the incidence of gastric cancer. Previous studies found that dysbiosis has been implicated in a wide range of diseases, while the role of gastric bacteria as a biomarker for AG has not been explored. Methods and Results Gastric juices from cases with non-atrophic gastritis (NAG) and AG were collected for investigation of bacterial composition and function. The β-diversity of microbiota exhibited a significant reduction in AG samples compared with that in NAG samples. Differential abundance analysis revealed that a total of 23 predicted species changed their distributions; meanwhile, all obligate anaerobic bacteria with a relatively high abundance lowered their contents in AG samples. Additionally, the correlation analysis indicated a clear shift in bacterial correlation pattern between the two groups. Functional interrogation of the gastric microbiota showed that bacterial metabolisms associated with enzyme families, digestive system, and endocrine system were downregulated in AG samples. The compositional dissection of “core microbiota” exhibited that oral pathogens, including Porphyromonas gingivalis, Campylobacter gracilis, and Granulicatella elegans, were magnified in AG samples, suggesting that oral diseases may be a trigger factor for early exacerbation of gastritis. Then, the differentially expressed bacteria were used as diagnostic biomarkers for the random forest classifier model for group prediction. Conclusions The results showed that bacterial biomarkers could distinguish AG patients from NAG cases with an accuracy of 90% at the genus level.

Background Perfluorodecanoic acid (PFDA) is a type of perfluoroalkyl acid (PFAA). PFDA has toxicity similar to dioxin; its effect on the body is not through a single target or a single pathway. However, the mechanism at the global level is still unclear. Methods and Results We treated mice with PFDA and characterized the global changes in gene expression in the liver using microarray analyses. The enriched KEGG pathways and GO analyses revealed that PFDA greatly affected the immune response, which was different from the response of gastric cells previously studied. As a proof of principle, the expressions of IL-1β and IL-18 were both decreased after PFDA treatment, and qRT-PCR and ELISAs verified the reduction of IL-1β and IL-18 in liver tissues. Mechanistic investigations indicated that PFDA inhibited caspase-1 activation, and decreased the mRNA levels of NLRP1, NLRP3, and NLRC4; thus, suggesting that inflammasome assemblies were suppressed. Further microarray data revealed that cIAP2 and its binding proteins, which are critical for regulating inflammasome assembly, were also repressed by PFDA. In addition, flow cytometry results revealed a significant inhibition of Th1 cell differentiation in the livers of PFDA-treated mice. Conclusions The results of this study suggested that one of the main toxic effects of PFDA on livers was the inhibition of immune response.

Whole body vibration (WBV) is a non-invasive physical therapy that has recently been included in the hospital's patient rehabilitation training catalog, but its health effects have not been sufficiently studied. In the present study, to examine the possible effects of WBV on immune cell differentiation, the IFN, IL-4,−17, F4/80 and CD3,−4,−8,−11b,−11c,−19 markers were used to characterizing the cells in mouse spleen. The results showed that the CD4 and CD25 positive lymphocytes in the spleen were significantly increased in the WBV group, and the population of Treg cells was enhanced significantly in response to WBV. Since the differentiation in immune cells is usually associated with microbiota, therefore the intestinal flora was characterized in mice and human individuals. The results indicated that WBV significantly reduced the α-diversity of mouse intestinal microbiota. Moreover, the principal coordinate analysis (PCoA) results indicated that the β-diversities of both mice and human fecal microbiota increased after WBV. Analysis of the bacterial composition indicated that the contents of a variety of bacteria changed in mice upon the stimulation of vibration, such as Lactobacillus animalis in mice, and Lactobacillus paraplantarum and Lactobacillus sanfranciscensis in human. The succeeding correlation analysis revealed that some bacteria with significant content variations were correlated to the regulatory T cell differentiation in mice and physical characteristics in human. Our research will provide the basis for future non-invasive treatment of microbial and immune related diseases.