Components Of Microbiota Research Articles

Air pollution accelerates the development of obesity and Alzheimer's disease: the role of leptin and inflammation -a mini-review.

Air pollution is an urgent concern linked to numerous health problems in low- and middle-income countries, where 92% of air pollution-related deaths occur. Particulate matter 2.5 (PM2.5) is the most harmful component of air pollutants, increasing inflammation and changing gut microbiota, favoring obesity, type 2 diabetes, and Alzheimer's Disease (AD). PM2.5 contains lipopolysaccharides (LPS), which can activate the Toll-like receptor 4 (TLR4) signaling pathway. This pathway can lead to the release of pro-inflammatory markers, including interleukins, and suppressor of cytokine signaling-3 (SOCS3), which inhibits leptin action, a hormone that keeps the energy homeostasis. Leptin plays a role in preventing amyloid plaque deposition and hyperphosphorylation of tau-protein (p-tau), mechanisms involved in the neurodegeneration in AD. Approximately 50 million people worldwide are affected by dementia, with a significant proportion living in low-and middle-income countries. This number is expected to triple by 2050. This mini-review focuses on the potential impact of PM2.5 exposure on the TLR4 signaling pathway, its contribution to leptin resistance, and dysbiosis that exacerbates the link between obesity and AD.

Infections caused by Slackia exigua: A single-center experience and literature review.

Slackia exigua, originally classified as Eubacterium exiguum, is a Gram-positive, asaccharolytic, rod-shaped anaerobic bacterium. The virulence factors of S. exigua have not been accurately identified. The objective of the study is to evaluate the pathogenic potential of S. exigua by presenting the cases of infections diagnosed at our hospital laboratory. Additionally, we reviewed the literature to summarize the experience with S. exigua infections to clarify, in the light of current knowledge, the clinical picture, diagnostic, and therapeutic issues related to this anaerobic bacterium. We reported eleven severe human infections caused by S. exigua. All patients required hospitalization. Nine of the cases involved chronic infections in the stomatognathic system, in two patients, skin infections were diagnosed. As it is known, S. exigua is a component of the human microbiota; however, it can cause opportunistic infections, particularly in the case of translocation outside its natural habitat. A critical literature analysis revealed that S. exigua can be responsible for bacteremia, meningitis, tissue necrosis, periprosthetic joint infection, and osteomyelitis. Several studies have been published regarding the determination of drug susceptibility of S. exigua. The isolated strains were susceptible to most antibiotics used for the treatment of anaerobic infections. The interpretation of antimicrobial susceptibility testing for some slow-growing in vitro, infrequently causing infections anaerobic bacteria, such as S. exigua, is based on The European Committee on Antimicrobial Susceptibility Testing (EUCAST) additional guidance taking into account the determination of drug susceptibility for groups of microorganisms for which cut-off values have not been developed.

Combining bioinformatics and multiomics strategies to investigate the key microbiota and active components of Liupao tea ameliorating hyperlipidemia

Ethnopharmacological relevanceHyperlipidemia as a major health issue has attracted much public attention. As a geographical indication product of China, Liupao tea (LPT) is a typical representative of traditional Chinese dark tea that has shown good potential in regulating glucose and lipid metabolism. LPT has important medicinal value in hyperlipidemia prevention. However, the active ingredients and metabolic mechanisms by which LPT alleviates hyperlipidemia remain unclear. Aim of the studyThis study aimed to systematically investigate the metabolic mechanisms and active ingredients of LPT extract in alleviating hyperlipidemia. Materials and methodsFirstly, we developed a mouse model of hyperlipidemia to study the pharmacodynamics of LPT. Subsequently, network pharmacology and molecular docking were performed to predict the potential key active ingredients and core targets of LPT against hyperlipidemia. LC-MS/MS was used to validate the identity of key active ingredients in LPT with chemical standards. Finally, the effect and metabolic mechanisms of LPT extract in alleviating hyperlipidemia were investigated by integrating metabolomic, lipidomic, and gut microbiome analyses. ResultsResults showed that LPT extract effectively improved hyperlipidemia by suppressing weight gain, remedying dysregulation of glucose and lipid metabolism, and reducing hepatic damage. Network pharmacology analysis and molecular docking suggested that four potential active ingredients and seven potential core targets were closely associated with roles for hyperlipidemia treatment. Ellagic acid, catechin, and naringenin were considered to be the key active ingredients of LPT alleviating hyperlipidemia. Additionally, LPT extract modulated the mRNA expression levels of Fxr, Cyp7a1, Cyp8b1, and Cyp27a1 associated with bile acid (BA) metabolism, mitigated the disturbances of BA and glycerophospholipid (GP) metabolism in hyperlipidemia mice. Combining fecal microbiota transplantation and correlation analysis, LPT extract effectively improved species diversity and abundance of gut microbiota, particularly the BA and GP metabolism-related gut microbiota, in the hyperlipidemia mice. ConclusionsLPT extract ameliorated hyperlipidemia by modulating GP and BA metabolism by regulating Lactobacillus and Dubosiella, thereby alleviating hyperlipidemia. Three active ingredients of LPT served as the key factors in exerting an improvement on hyperlipidemia. These findings provide new insights into the active ingredients and metabolic mechanisms of LPT in improving hyperlipidemia, suggesting that LPT can be used to prevent and therapeutic hyperlipidemia.

Developmental Programming of the Fetal Immune System by Maternal Western-Style Diet: Mechanisms and Implications for Disease Pathways in the Offspring.

Maternal obesity and over/undernutrition can have a long-lasting impact on offspring health during critical periods in the first 1000 days of life. Children born to mothers with obesity have reduced immune responses to stimuli which increase susceptibility to infections. Recently, maternal western-style diets (WSDs), high in fat and simple sugars, have been associated with skewing neonatal immune cell development, and recent evidence suggests that dysregulation of innate immunity in early life has long-term consequences on metabolic diseases and behavioral disorders in later life. Several factors contribute to abnormal innate immune tolerance or trained immunity, including changes in gut microbiota, metabolites, and epigenetic modifications. Critical knowledge gaps remain regarding the mechanisms whereby these factors impact fetal and postnatal immune cell development, especially in precursor stem cells in bone marrow and fetal liver. Components of the maternal microbiota that are transferred from mothers consuming a WSD to their offspring are understudied and identifying cause and effect on neonatal innate and adaptive immune development needs to be refined. Tools including single-cell RNA-sequencing, epigenetic analysis, and spatial location of specific immune cells in liver and bone marrow are critical for understanding immune system programming. Considering the vital role immune function plays in offspring health, it will be important to understand how maternal diets can control developmental programming of innate and adaptive immunity.

Association between gut microbiota and anxiety disorders: a bidirectional two-sample mendelian randomization study.

There are many articles reporting that the component of intestinal microbiota implies a link to anxiety disorders (AD), and the brain-gut axis is also a hot topic in current research. However, the specific relevance between gut microbiota and AD is uncertain. We aimed to investigate causal relationship between gut microbiota and AD by using bidirectional Mendelian randomization (MR). Genetic instrumental variable (IV) for the gut microbiota were obtained from a genome-wide association study (GWAS) involving 18,340 participants. Summary data for AD were derived from the GWAS and included 158,565 cases and 300,995 controls. We applied the inverse variance weighted (IVW) method as the main analysis. Cochran's Q values was computed to evaluate the heterogeneity among IVs. Sensitivity analyses including intercept of MR-Egger method and MR-PRESSO analysis were used to test the horizontal pleiotropy. We discovered 9 potential connections between bacterial traits on genus level and AD. Utilizing the IVW method, we identified 5 bacterial genera that exhibited a direct correlation with the risk of AD: genus Eubacteriumbrachygroup, genus Coprococcus3, genus Enterorhabdus, genus Oxalobacter, genus Ruminiclostridium6. Additionally, we found 4 bacterial genera that exhibited a negative association with AD: genus Blautia, genus Butyricicoccus, genus Erysipelotrichaceae-UCG003 and genus Parasutterella. The associations were confirmed by the sensitivity analyses. Our study found a causal relation between parts of the gut microbiota and AD. Further randomized controlled trials are crucial to elucidate the positive effects of probiotics on AD and their particular protection systems.

Relationship between gut microbiome and bone deficits in primary hyperparathyroidism: A proof-of-concept pilot study.

Parathyroid hormone (PTH) interacts with components of the gut microbiota to exert its bone-regulating effects. This study aimed to investigate the gut microbial composition in patients with primary hyperparathyroidism (PHPT). Nine patients with PHPT and nine age-sex and body mass index-matched healthy controls were included. Gut microbial composition was assessed using 16S rRNA gene amplicon sequencing in both groups at baseline and 1 month after parathyroidectomy in the PHPT group. Data were imported into QIIME-2 and both QIIME-2 and R packages were used for microbiome analysis. Alpha and beta diversities were similar between the groups and remained unchanged after parathyroidectomy. The relative abundance of Subdoligranulum was significantly higher, whereas Ruminococcus, Alloprevotella, Phascolarctobacterium, and Clostridium sensu stricto_1 were significantly lower in PHPT than in controls (p < 0.001). After parathyroidectomy, the relative abundance of Subdoligranulum decreased, and Ruminococcus and Alloprevotella increased (p < 0.001). The PHPT group had lower total femoral and lumbar bone mineral density (BMD) than the controls (p < 0.05). At baseline, Alloprevotella abundance was positively correlated with serum phosphorus and Subdoligranulum was positively correlated with total lumbar BMD. Clostridium sensu stricto_1 was negatively correlated with serum calcium and positively correlated with femoral neck BMD. Postoperatively, Alloprevotella was positively correlated with baseline serum phosphorus and Phascolarctobacterium was positively correlated with distal radius BMD. This study demonstrated that the diversity of the gut microbiome was altered, possibly in response to electrolyte changes in PHPT, both before and after parathyroidectomy.

Alterations in the gut mycobiome with coronary artery disease severity

BackgroundCoronary artery disease (CAD) is a prevalent cardiovascular condition, and numerous studies have linked gut bacterial imbalance to CAD. However, the relationship of gut fungi, another essential component of the intestinal microbiota, with CAD remains poorly understood. MethodsIn this cross-sectional study, we analyzed fecal samples from 132 participants, split into 31 healthy controls and 101 CAD patients, further categorized into stable CAD (38), unstable angina (41), and acute myocardial infarction (22) groups. We conducted internal transcribed spacer 1 (ITS1) and 16S sequencing to examine gut fungal and bacterial communities. FindingsBased on ITS1 analyses, Ascomycota and Basidiomycota were the dominant fungal phyla in all the groups. The α diversity of gut mycobiome remained unaltered among the control group and CAD subgroups; however, the structure and composition of the mycobiota differed significantly with the progression of CAD. The abundances of 15 taxa gradually changed with the occurrence and progression of the disease and were significantly correlated with major CAD risk factor indicators. The mycobiome changes were closely linked to gut microbiome dysbiosis in patients with CAD. Furthermore, disease classifiers based on gut fungi effectively identified subgroups with different degrees of CAD. Finally, the FUNGuild analysis further categorized these fungi into distinct ecological guilds. InterpretationIn conclusion, the structure and composition of the gut fungal community differed from healthy controls to various subtypes of CAD, revealing key fungi taxa alterations linked to the onset and progression of CAD. Our study highlights the potential role of gut fungi in CAD and may facilitate the development of novel biomarkers and therapeutic targets for CAD. FundingThis work was supported by the grants from the National Natural Science Foundation of China (No. 82170302, 92168117, 82370432), National clinical key specialty construction project- Cardiovascular Surgery, 2024 Reform and Development Program of Beijing Institute of Respiratory Medicine, the Beijing Natural Science Foundation (No. 7222068); the Reform and Development Program of Beijing Institute of Respiratory Medicine (No. Ggyfz202308); and the Clinical Research Incubation Program of Beijing Chaoyang Hospital Affiliated to Capital Medical University (No. CYFH202209).

Multiomics integration identifies regulatory factors underlying reproductive disorders in geese1

Geese, descendants of migratory birds, have preserved the distinct reproductive and lipid metabolism traits of their wild ancestors. Therefore, compared to other poultry, geese have lower egg production ability and a more sensitive susceptibility to fatty liver. Recent research underscores the impact of lipid metabolism disorders on female reproductive health. In this context, we observed reproductive disorders (RD) and lipid metabolism anomalies in certain geese populations. This study systematically elucidated the differences between RD and normal geese at various levels, including genomics, transcriptomics, bile acid metabolomics, and microbiomics, revealing the crucial role of microorganisms. Our study provides a thorough examination of the ovarian anatomical, histological, and transcriptomic profiles between normal and RD geese. Genomic analyses pinpoint mutations in genes associated with bile acid metabolism, highlighting their potential role in RD pathogenesis. The genomic discoveries are substantiated by precise bile acid assays and ileum transcriptome analyses, which expose a significant disruption in bile acid absorption, activation of FXR, and an increase in serum chenodeoxycholic acid (CDCA) concentrations within RD geese. Notably, 16S rRNA sequencing uncovers significantly greater beta diversity in the ileum microbiota of RD geese as compared to the normal group. Both Wilcoxon rank sum test and LEfSe analyses highlighted a marked increase in Romboutsia abundance in RD geese. Experimental cultivation of microbiota with CDCA supplementation confirms the impact of CDCA on Romboutsia lituseburensis (R. lituseburensis) proliferation. Gavage experiments with R. lituseburensis elucidates its involvement in primary follicle reduction via immune-mediated pathways. Collectively, our multi-faceted analysis unravels the intricate involvement of Romboutsia in goose RD, offering insights from genetic, physiological, and microbial dimensions. Our findings not only deepen our understanding of the etiology of RD in geese but also suggest potential avenues for therapeutic interventions targeting bile acid metabolism and the modulation of specific microbiota components.

Oral Mycobiota: A Narrative Review.

Numerous studies have proven the important role of the oral microbiota in health and disease. The dysfunctionality of the oral microbiota, known as dysbiosis, is incriminated in dental caries, periodontal disease, oral infectious diseases, oral cancer, and systemic disease. The lesser-known component of the oral microbiota, the mycobiota, is now assiduously investigated. Recent technological developments have helped foster the identification of new fungal species based on genomic research. Next-generation sequencing has expanded our knowledge about the diversity, architecture, and relationships of oral microorganisms within the oral cavity. The mycobiome structure and relationships with the bacteriome have been studied to identify a mycobiotic signature. This review aimed to emphasize the latest knowledge of the oral mycobiome.

The role of CXCL2-mediated crosstalk between tumor cells and macrophages in Fusobacterium nucleatum-promoted oral squamous cell carcinoma progression

Dysbiosis of the oral microbiota is related to chronic inflammation and carcinogenesis. Fusobacterium nucleatum (Fn), a significant component of the oral microbiota, can perturb the immune system and form an inflammatory microenvironment for promoting the occurrence and progression of oral squamous cell carcinoma (OSCC). However, the underlying mechanisms remain elusive. Here, we investigated the impacts of Fn on OSCC cells and the crosstalk between OSCC cells and macrophages. 16 s rDNA sequencing and fluorescence in situ hybridization verified that Fn was notably enriched in clinical OSCC tissues compared to paracancerous tissues. The conditioned medium co-culture model validated that Fn and macrophages exhibited tumor-promoting properties by facilitating OSCC cell proliferation, migration, and invasion. Besides, Fn and OSCC cells can recruit macrophages and facilitate their M2 polarization. This crosstalk between OSCC cells and macrophages was further enhanced by Fn, thereby amplifying this positive feedback loop between them. The production of CXCL2 in response to Fn stimulation was a significant mediator. Suppression of CXCL2 in OSCC cells weakened Fn’s promoting effects on OSCC cell proliferation, migration, macrophage recruitment, and M2 polarization. Conversely, knocking down CXCL2 in macrophages reversed the Fn-induced feedback effect of macrophages on the highly invasive phenotype of OSCC cells. Mechanistically, Fn activated the NF-κB pathway in both OSCC cells and macrophages, leading to the upregulation of CXCL2 expression. In addition, the SCC7 subcutaneous tumor-bearing model in C3H mice also substantiated Fn’s ability to enhance tumor progression by facilitating cell proliferation, activating NF-κB signaling, up-regulating CXCL2 expression, and inducing M2 macrophage infiltration. However, these effects were reversed by the CXCL2-CXCR2 inhibitor SB225002. In summary, this study suggests that Fn contributes to OSCC progression by promoting tumor cell proliferation, macrophage recruitment, and M2 polarization. Simultaneously, the enhanced CXCL2-mediated crosstalk between OSCC cells and macrophages plays a vital role in the pro-cancer effect of Fn.

Infekcje wywołane przez Slackia exigua. Przegląd literatury i obserwacje własne

Slackia exigua, originally classified as Eubacterium exiguum, is a Gram-positive, asaccharolytic, rod-shaped anaerobic bacterium. The virulence factors of S. exigua have not been accurately identified. The objective of the study is to evaluate the pathogenic potential of S. exigua by presenting the cases of infections diagnosed at our hospital laboratory. Additionally, we reviewed the literature to summarize the experience with S. exigua infections to clarify, in the light of current knowledge, the clinical picture, diagnostic, and therapeutic issues related to this anaerobic bacterium. We reported eleven severe human infections caused by S. exigua. All patients required hospitalization. Nine of the cases involved chronic infections in the stomatognathic system, in two patients, skin infections were diagnosed. As it is known, S. exigua is a component of the human microbiota; however, it can cause opportunistic infections, particularly in the case of translocation outside its natural habitat. A critical literature analysis revealed that S. exigua can be responsible for bacteremia, meningitis, tissue necrosis, periprosthetic joint infection, and osteomyelitis. Several studies have been published regarding the determination of drug susceptibility of S. exigua. The isolated strains were susceptible to most antibiotics used for the treatment of anaerobic infections. The interpretation of antimicrobial susceptibility testing for some slow-growing in vitro, infrequently causing infections anaerobic bacteria, such as S. exigua, is based on The European Committee on Antimicrobial Susceptibility Testing (EUCAST) additional guidance taking into account the determination of drug susceptibility for groups of microorganisms for which cut-off values have not been developed.

Gut microbiota-astrocyte axis: new insights into age-related cognitive decline.

With the rapidly aging human population, age-related cognitive decline and dementia are becoming increasingly prevalent worldwide. Aging is considered the main risk factor for cognitive decline and acts through alterations in the composition of the gut microbiota, microbial metabolites, and the functions of astrocytes. The microbiota-gut-brain axis has been the focus of multiple studies and is closely associated with cognitive function. This article provides a comprehensive review of the specific changes that occur in the composition of the gut microbiota and microbial metabolites in older individuals and discusses how the aging of astrocytes and reactive astrocytosis are closely related to age-related cognitive decline and neurodegenerative diseases. This article also summarizes the gut microbiota components that affect astrocyte function, mainly through the vagus nerve, immune responses, circadian rhythms, and microbial metabolites. Finally, this article summarizes the mechanism by which the gut microbiota-astrocyte axis plays a role in Alzheimer's and Parkinson's diseases. Our findings have revealed the critical role of the microbiota-astrocyte axis in age-related cognitive decline, aiding in a deeper understanding of potential gut microbiome-based adjuvant therapy strategies for this condition.

Exploring the molecular mechanisms and shared gene signatures between celiac disease and ulcerative colitis based on bulk RNA and single-cell sequencing: Experimental verification

Many immune-mediated diseases have the common genetic basis, as an autoimmune disorder, celiac disease (CeD) primarily affects the small intestine, and is caused by the ingestion of gluten in genetically susceptible individuals. As for ulcerative colitis (UC), which most likely involves a complex interplay between some components of the commensal microbiota and other environmental factors in its origin. These two autoimmune diseases share a specific target organ, the bowel. The etiology and immunopathogenesis of both conditions characterized by chronic intestinal inflammation, ulcerative colitis and celiac disease, are not completely understood. Both are complex diseases with genetics and the environmental factors contributing to dysregulation of innate and adaptive immune responses, leading to chronic inflammation and disease. This study is designed to further clarify the relationship between UC and CeD. The GEO database was used to download gene expression profiles for CeD (GSE112102) and UC (GSE75214). The GSEA KEGG pathway analysis revealed that immune-related pathways were significantly associated with both diseases. Further, we screened 187 shared differentially expressed genes (DEGs) of the two diseases. Gene Ontology (GO) and WikiPathways were carried out to perform the biological process and pathway enrichment analysis. Subsequently, based on the DEGs, the least absolute shrinkage and selection operator (LASSO) analysis was performed to screen for the diagnostic biomarkers of the diseases. Moreover, single-cell RNA-sequencing (RNA-seq) data from five colonic propria with UC showed that REG4 expression was present in Goblet cell, Enteroendocrine cell, and Epithelial. Finally, our work identified REG4 is the shared gene of UC and CeD via external data validation, cellular experiments, and immunohistochemistry. In conclusion, our study elucidated that abnormal immune response could be the common pathogenesis of UC and CeD, and REG4 might be a key potential biomarker and therapeutic target for the comorbidity of these two diseases.

Abstract PL03-02: From microniches to single cells: Understanding the impact of intratumoral microbes on spatial and cellular heterogeneity in cancer

Abstract The tumor microenvironment (TME) is a dynamic network that includes a variety of non-malignant cells such as endothelial cells, fibroblasts, and immune cells, which play a crucial role in tumor behavior. Advances in molecular analysis have recently identified the presence of intratumoral microbiota in several solid cancer types. However, the specific ways these microorganisms interact with human cells within the TME and contribute to disease progression are not yet fully understood. Our recent research provides new insights into how bacterial components of the intratumoral microbiota contribute to tumor heterogeneity, particularly in head and neck and colorectal cancers. To investigate these interactions, we have adapted and applied emerging technologies in spatial transcriptomics, spatial proteomics, and single-cell sequencing (INVADEseq). Our spatial analyses show that the intratumoral microbiota are not distributed randomly within human tumors; instead, they localize to distinct microniches that promote immune and epithelial cell functions supportive of cancer progression. These bacterial-colonized microniches are characterized by myeloid cell infiltration, upregulation of MAPKs and immune checkpoint proteins, and reduced T-cell levels. Furthermore, INVADEseq single-cell RNA sequencing has enabled us to identify the dominant host cell-associated bacteria, the human cell types they infect, and their impact on the transcriptional programs of infected cells from patient tumor specimens. In oral squamous cell carcinoma, Fusobacterium and Treponema species have been identified as the dominant cell-associated bacterial taxa, primarily infecting subsets of macrophages and aneuploid cancer epithelial cells and upregulating pathways associated with cancer progression. Our findings offer insights into the complex interplay between intratumoral microbiota and human components of the TME, emphasizing their role in supporting intratumoral heterogeneity and influencing cancer progression. Understanding these dynamics holds significant promise for the development of targeted therapeutic strategies aimed at disrupting bacterial-human spatial and cellular interactions within the TME. Citation Format: Susan Bullman. From microniches to single cells: Understanding the impact of intratumoral microbes on spatial and cellular heterogeneity in cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 2 (Late-Breaking, Clinical Trial, and Invited Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(7_Suppl):Abstract nr PL03-02.

Effects of host identity on the gut microbiota: A comparative study on three microtinae species.

Gut microbiota exert an immense effect on host health and host environmental adaptation. Furthermore, the composition and structure of gut microbiota are determined by the environment and host genetic factors. However, the relative contribution of the environment and host genetic factors toward shaping the structure of gut microbiota has been poorly understood. In this study, we characterized the fecal microbial communities of the closely related voles Neodon fuscus, Lasiopodomys brandtii, and L. mandarinus after caged feeding in the laboratory for 6 months, through high-throughput sequencing and bioinformatics analysis. The results of pairwise comparisons of N. fuscus vs. L. brandtii and L. mandarinus vs. L. brandtii revealed significant differences in bacterial diversity and composition after domestication. While 991 same operational taxonomic units (OTUs) were shared in three voles, there were 362, 291, and 303 species-specific OTUs in N. fuscus, L. brandtii, and L. mandarinus, respectively. The relative abundances of Proteobacteria and Prevotella, which are reported to be enriched in high-altitude populations, were significantly higher in high-altitude N. fuscus than in low-altitude L. brandtii after domestication. Firmicutes, which produce various digestive enzymes for energy metabolism, and Spirochaetes, which can degrade cellulose, were found in higher abundance in subterranean L. mandarinus than thatin L. brandtii which dwells on the earth surface. Our findings showed that some components of gut microbiota still maintained dominance even when different host species are reared under the same environmental conditions, suggesting that these bacteria are substantially influenced by host factors.

Imbalance of gut microbiota in gestational diabetes

AimTo investigate the differences in gut microbiota composition among nonpregnant women of reproductive age, healthy pregnant women, and gestational diabetes (GD) patients.MethodsA total of 45 outpatients were enrolled and divided into three groups: nonpregnant women of reproductive age (control group, n = 23), healthy pregnant women (normal group, n = 10), and GD patients (GD group, n = 12). Faecal samples were collected and sequenced using 16S rRNA gene sequencing to analyse the microbial composition.Results(1) Pregnant patients exhibited an increase in the abundance of Streptococcus (Pnormal = 0.01286, PGD = 0.002965) and Blautia (Pnormal = 0.0003924, PGD = 0.000246) but a decrease in the abundance of Roseburia (Pnormal = 0.0361, PGD = 0.007075), Phascolarctobacterium (Pnormal = 0.0003906, PGD = 0.02499) and Lachnoclostridium (Pnormal = 0.0003906, PGD = 0.03866). (2) Compared with healthy pregnant women, GD patients had an excessive increase in Streptococcus abundance and decrease in Roseburia abundance. The increase in Blautia abundance and the decrease in Phascolarctobacterium and Lachnoclostridium abundance in GD patients were less than those in healthy pregnant women. (3) The abundance of Faecalibacterium prausnitzii decreased significantly in GD patients (PGD = 0.02985) but not in healthy pregnant patients (Pnormal = 0.1643).ConclusionsAbnormal increases and decreases in the abundances of gut microbiota components, especially Faecalibacterium prausnitzii, were observed in GD patients.Trial registrationThe cross-sectional research was conducted in accordance with the Declaration of Helsinki, and approved by Sir Run Run Shaw Hospital Clinical Trials and Biomedical Ethics Committee. The study has been registered in the Chinese Clinical Trial Registry (ChiCTR1900026164, 24/09/2019, http://www.chictr.org.cn/showproj.aspx?proj=43,455).

Unraveling intestinal microbiota's dominance in polycystic ovary syndrome pathogenesis over vaginal microbiota.

Polycystic ovary syndrome (PCOS) is a prevalent endocrine disease in women, intricately linked to hormonal imbalances. The microbiota composition plays a pivotal role in influencing hormonal levels within the body. In this study, we utilized a murine model to investigate how intestinal and vaginal microbiota interact with hormones in the development of PCOS. Twenty female mice were randomly assigned to the normal group (N) and the model group (P), where the latter received daily subcutaneous injections of 0.1 mL DHEA (6 mg/100 g). Throughout the experiment, we evaluated the PCOS mouse model by estrus cycle, serum total testosterone (T), prolactin (PRL) and luteinizing hormone (LH) levels, and ovarian pathological morphology. The microbial composition in both intestinal content and vaginal microbiota were studied by 16S rRNA gene high-throughput sequencing. Compared with the N group, the P group showed significant increases in body weight, T, and PRL, with significant decrease in LH. Ovaries exhibited polycystic changes, and the estrous cycle was disrupted. The intestinal microbiota result shows that Chao1, ACE, Shannon and Simpson indexes were decreased, Desulfobacterota and Acidobacteriota were increased, and Muribaculaceae, Limosilactobacillus and Lactobacillus were decreased in the P group. T was significantly positively correlated with Enterorhabdus, and LH was significantly positively correlated with Lactobacillus. The analysis of vaginal microbiota revealed no significant changes in Chao1, ACE, Shannon, and Simpson indices. However, there were increased in Firmicutes, Bacteroidota, Actinobacteriota, Streptococcus, and Muribaculaceae. Particularly, Rodentibacter displayed a robust negative correlation with other components of the vaginal microbiota. Therefore, the response of the intestinal microbiota to PCOS is more significant than that of the vaginal microbiota. The intestinal microbiota is likely involved in the development of PCOS through its participation in hormonal regulation.

Women health and microbiota: Different aspects of well-being

In this editorial, we comment on the article by Marano et al recently published in the World Journal of Gastroenterology 2023; 29 (45): 5945-5952. We focus on the role of gut microbiota (GM) in women’s health, highlighting the need to thoroughly comprehend the sex differences in microbiota. Together, the host and GM support the host’s health. The microbiota components consist of viruses, bacteria, fungi, and archaea. This complex is an essential part of the host and is involved in neurological development, metabolic control, immune system dynamics, and host dynamic homeostasis. It has been shown that differences in the GM of males and females can contribute to chronic diseases, such as gastrointestinal, metabolic, neurological, cardiovascular, and respiratory illnesses. These differences can also result in some sex-specific changes in immunity. Every day, research on GM reveals new and more expansive frontiers, offering a wealth of innovative opportunities for preventive and precision medicine.

Akkermansia muciniphila and Parabacteroides distasonis synergistically protect from colitis by promoting ILC3 in the gut.

The contribution of the gut microbiome to the balance between homeostasis and inflammation is widely known. Nevertheless, the etiology of inflammatory bowel disease, which is known to be influenced by genetics, immune response, and environmental cues, remains unclear. Unlocking novel players involved in the dictation of a protective gut, namely, in the microbiota component, is therefore crucial to develop novel strategies to tackle IBD. Herein, we revealed a synergistic interaction between two commensal bacterial strains, Akkermansia muciniphila and Parabacteroides distasonis, which induce protection against both acute and chronic models of colitis induction, by enhancing epithelial barrier integrity and promoting group 3 innate lymphoid cells in the colonic mucosa. This study provides a novel insight on how commensal bacteria can beneficially act to promote intestinal homeostasis, which may open new avenues toward the use of microbiome-derived strategies to tackle IBD.

Histone acylations as a mechanism for regulation of intestinal epithelial cells.

Histone post-translational modifications are reversible epigenetic mechanisms that regulate chromatin structure and gene transcription. In recent years, in addition to the well-characterized histone acetylation, new acylations such as propionylation, crotonylation, butyrylation and beta-hydroxybutyrylation have been described and explored in different cell types at contexts of health and disease. Understanding how histone acylations contribute to gene expression regulation is especially important in intestinal epithelial cells (IECs) because they receive many different signals from other cells and the external environment and must adapt to maintain essential functions such as nutrient and water absorption, maintenance of tolerance and protection against pathogens. In this review, we describe how cells regulate these modifications, how they are recognized by other proteins and impact gene expression. We summarize recent studies that explored the role of these distinct epigenetic marks in the regulation of IECs and discuss their biological importance for the intestinal epithelium's adaptations to changes in metabolism and to respond to environmental signals provided, for example, by the diet, components of the intestinal microbiota and pathogens. Finally, we discuss how the histone acylations are affected by inflammatory signals and how this knowledge may provide new targets for treatment of pathologies such as the inflammatory bowel diseases.