Specific Bacterial Taxa Research Articles

Microbiota and Autism: A Review on Oral and Gut Microbiome Analysis Through 16S rRNA Sequencing

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition with multifactorial etiologies, including genetic, environmental, and microbiological factors. In recent years, increasing attention has been given to the role of the gut microbiota in ASD. Emerging evidence suggests that gut microbiota dysbiosis may influence the central nervous system through the gut-brain axis, potentially impacting behavior and neurodevelopment. The use of 16S rRNA gene sequencing has become a pivotal tool in profiling the microbial communities associated with ASD, offering valuable insights into bacterial diversity, composition, and potential functional roles. This review aims to provide a comprehensive analysis of current findings on the relationship between the gut and oral microbiota with ASD, and a particular focus on studies utilizing 16S rRNA sequencing. We will explore how gut microbiome alterations may contribute to ASD pathophysiology, discuss the limitations of existing research, and propose future directions for the integration of microbiome analysis in ASD diagnostics and treatment strategies. These findings underscore the potential role of microbiota in modulating ASD symptoms. The data suggest that specific bacterial taxa are consistently altered in ASD, which may have implications for understanding the gut-brain axis and its influence on neurodevelopment.

Depletion of core microbiome forms the shared background against diverging dysbiosis patterns in Crohn’s disease and intestinal tuberculosis: insights from an integrated multi-cohort analysis

Background/aimsCrohn’s disease (CD) and intestinal tuberculosis (ITB) are gastrointestinal (GI) inflammatory disorders with overlapping clinical presentations but diverging etiologies. The study aims to decipher CD and ITB-associated gut dysbiosis signatures and identify disease-associated co-occurring modules to evaluate whether this dysbiosis signature is a disease-specific trait or is a shared feature across diseases of diverging etiologies.MethodsDisease-associated gut microbial modules were identified using statistical machine learning and co-abundance network analysis in controls, CD and ITB patients recruited as part of this study. Module reproducibility was reinvestigated through meta-network analysis encompassing >5400 bacteriomes and ~900 mycobiomes. Subsequently, >1600 Indian gut microbiomes were analyzed to identify a central-core gut microbiome of 46 taxa, whose abundances aided in the formulation of an India-specific Core Gut Microbiome Score (CGMS) to measure the degree of core retention.ResultsBoth diseases witness similar patterns of alterations in [alpha]-diversity, characterized by a significant reduction in gut bacterial (i.e., bacterial/archaeal) diversity and a concomitant increase in the fungal [alpha]-diversity. Specific bacterial taxa, along with the diverging mycobiome enabled distinction between the diseases. Co-abundance network analysis of these taxa, validated by integrated meta-network analysis, revealed a ‘disease-depleted’ module, consistent across multiple cohorts, with >75% of this module constituting the central-core Indian gut microbiome. CGMS robustly assessed the core-microbiome loss across different stages of gut inflammatory disorders, in Indian and international cohorts.ConclusionsWhile the disease-specific gain of detrimental bacteria forms an important component of gut dysbiosis, loss of the core microbiome is a shared phenomenon contributing to various GI disorders.

Associations between dietary fibers and gut microbiome composition in the EDIA longitudinal infant cohort

BackgroundThe infant gut microbiome undergoes rapid changes in the first year of life, supporting normal development and long-term health. Although diet shapes this process, the role of fibers in complementary foods on gut microbiome maturation is poorly understood. ObjectivesWe explored how the transition from human milk to fibers in complementary foods shapes the taxonomic and functional maturation of the gut microbiome within the first year of life. MethodsWe assessed the longitudinal and cross-sectional development of infant gut microbiomes (N = 68 infants) and metabolomes (N = 33 infants) using linear mixed models to uncover their associations to dietary fibers and their food sources. Fiber intakes were assessed with 3-d food records (months 3, 6, 9, and 12) relying on CODEX-compliant fiber fraction values, and questionnaires tracked the overall complementary food introduction. Bacterial species were identified and quantified via MetaPhlAn2 from metagenomic data, and metabolomic profiles were obtained using 4 LC-MS methods. ResultsWe identified 176 complementary food fiber-bacterial species associations. First plant-based fibers associated with microbiota compositions similar to breastfeeding, and further associated with aromatic amino acid metabolites, including 5-hydroxyindoleacetic acid (total dietary fiber – complementary foods (g) – β = 3.50, CI: 2.48, 4.52, P = 6.53 × 10–5). Distinct fibers from different food categories showed unique associations with specific bacterial taxa. Key species, such as Faecalibacterium prausnitznii, associated with oat fibers (g/MJ, β = 2.18, confidence interval: 1.36, 2.84, P = 6.12 × 10–6), reflective of maturing microbial communities. Fiber intake during weaning associated with shifts in metabolite profiles, including immunomodulatory metabolites, with fiber effects observed in a source- and timing-dependent manner, implicated in gradual microbiome diversification. ConclusionsIntroducing complementary dietary fibers during the weaning period supports gut microbiome diversification and stabilization. Even minor dietary variations shows significant associations with microbial taxa and functions from the onset of weaning, highlighting the importance of infant dietary recommendations that support the gut microbiome maturation during early life.This trial was registered at clinicaltrials.gov as registration number NCT01735123.

Changes in Gut Microbial Composition and DNA Methylation in Obese Patients with NAFLD After Bariatric Surgery.

This study investigates the effects of bariatric surgery on non-alcoholic fatty liver disease (NAFLD) by examining the interplay between gut microbiota, epigenetics, and metabolic health. A cohort of 22 patients undergoing sleeve gastrectomy (SG) was analyzed for changes in gut microbial composition and DNA methylation profiles before and six months after surgery. Correlations between gut microbial abundance and clinical markers at baseline revealed that certain genera were associated with worse metabolic health and liver markers. Following SG, significant improvements were observed in the clinical, anthropometric, and biochemical parameters of the NAFLD patients. Although alpha-diversity indices (i.e., Chao1, Simpson, Shannon) did not show significant changes, beta-diversity analysis revealed a slight shift in microbial composition (PERMANOVA, p = 0.036). Differential abundance analysis identified significant changes in specific bacterial taxa, including an increase in beneficial Lactobacillus species such as Lactobacillus crispatus and Lactobacillus iners and a decrease in harmful taxa like Erysipelotrichia. Additionally, DNA methylation analysis revealed 609 significant differentially methylated CpG sites between the baseline values and six months post-surgery, with notable enrichment in genes related to the autophagy pathway, such as IRS4 and ATG4B. The results highlight the individualized responses to bariatric surgery and underscore the potential for personalized treatment strategies. In conclusion, integrating gut microbiota and epigenetic factors into NAFLD management could enhance treatment outcomes, suggesting that future research should explore microbiome-targeted therapies and long-term follow-ups on liver health post-surgery.

Novelties on Neuroinflammation in Alzheimer's Disease-Focus on Gut and Oral Microbiota Involvement.

Recent studies underscore the role of gut and oral microbiota in influencing neuroinflammation through the microbiota-gut-brain axis, including in Alzheimer's disease (AD). This review aims to provide a comprehensive synthesis of recent findings on the involvement of gut and oral microbiota in the neuroinflammatory processes associated with AD, emphasizing novel insights and therapeutic implications. This review reveals that dysbiosis in AD patients' gut and oral microbiota is linked to heightened peripheral and central inflammatory responses. Specific bacterial taxa, such as Bacteroides and Firmicutes in the gut, as well as Porphyromonas gingivalis in the oral cavity, are notably altered in AD, leading to significant changes in microglial activation and cytokine production. Gut microbiota alterations are associated with increased intestinal permeability, facilitating the translocation of endotoxins like lipopolysaccharides (LPS) into the bloodstream and exacerbating neuroinflammation by activating the brain's toll-like receptor 4 (TLR4) pathways. Furthermore, microbiota-derived metabolites, including short-chain fatty acids (SCFAs) and amyloid peptides, can cross the blood-brain barrier and modulate neuroinflammatory responses. While microbial amyloids may contribute to amyloid-beta aggregation in the brain, certain SCFAs like butyrate exhibit anti-inflammatory properties, suggesting a potential therapeutic avenue to mitigate neuroinflammation. This review not only highlights the critical role of microbiota in AD pathology but also offers a ray of hope by suggesting that modulating gut and oral microbiota could represent a novel therapeutic strategy for reducing neuroinflammation and slowing disease progression.

The Role of Gut Microbiota in the Efficacy and Side Effect Profile of Biologic Therapies for Autoimmune Diseases.

The role of gut microbiota in influencing the efficacy and side effect profile of biological therapies for autoimmune diseases has gained increasing attention. Understanding these interactions is crucial for optimizing treatment outcomes and minimizing adverse events associated with biological therapies. This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We comprehensively analyzed studies involving human subjects with autoimmune diseases treated with biological therapies. Data on gut microbiota composition, therapeutic efficacy, and side effect profiles were extracted and synthesized to assess the impact of microbiota on treatment outcomes. Our review identified a significant relationship between gut microbiota composition and the efficacy of biological therapies. Specific bacterial taxa, such as Clostridiales and Roseburia inulinivorans, were associated with improved therapeutic responses, while alterations in microbiota were linked to increased adverse events. The predictive potential was demonstrated with microbiota signatures correlating with treatment success and side effects, highlighting the relevance of microbial profiles in therapeutic outcomes. The findings suggest that gut microbiota plays a pivotal role in modulating the efficacy and side effect profile of biological therapies for autoimmune diseases. Integrating microbiota assessments into clinical practice could enhance personalized treatment strategies and improve patient outcomes.

Impact of doxycycline post-exposure prophylaxis for sexually transmitted infections on the gut microbiome and antimicrobial resistome.

Doxycycline post-exposure prophylaxis (doxy-PEP) reduces bacterial sexually transmitted infections among men who have sex with men and transgender women. Although poised for widespread clinical implementation, the impact of doxy-PEP on antimicrobial resistance remains a primary concern as its effects on the gut microbiome and resistome, or the antimicrobial resistance genes (ARGs) present in the gut microbiome, are unknown. To investigate these effects, we studied participants from the DoxyPEP trial, a randomized clinical trial comparing doxy-PEP use, a one-time doxycycline 200-mg dose taken after condomless sex (DP arm, n = 100), to standard of care (SOC arm, n = 50) among men who have sex with men and transgender women. From self-collected rectal swabs at enrollment (day-0) and after 6 months (month-6), we performed metagenomic DNA sequencing (DNA-seq) or metatranscriptomic RNA sequencing (RNA-seq). DNA-seq data were analyzable from 127 samples derived from 89 participants, and RNA-seq data were analyzable from 86 samples derived from 70 participants. We compared the bacterial microbiome and resistome between the two study arms and over time. The median number of doxycycline doses taken since enrollment by participants with DNA-seq data was zero (interquartile range (IQR): 0-7 doses) for the SOC arm and 42 (IQR: 27-64 doses) for the DP arm. Tetracycline ARGs were detected in all day-0 DNA-seq samples and in 85% of day-0 RNA-seq samples. The proportional mass of tetracycline ARGs in the resistome increased between day-0 and month-6 in DP participants from 46% to 51% in the metagenome (P = 2.3 × 10-2) and from 4% to 15% in the metatranscriptome (P = 4.5 × 10-6), but no statistically significant increases in other ARG classes were observed. Exposure to a higher number of doxycycline doses correlated with proportional enrichment of tetracycline ARGs in the metagenome (Spearman's ρ = 0.23, P = 9.0 × 10-3) and metatranscriptome (Spearman's ρ = 0.55, P = 3.7 × 10-8). Bacterial microbiome alpha diversity, beta diversity and total bacterial mass did not differ between day-0 and month-6 samples from DP participants when assessed by either DNA-seq or RNA-seq. In an abundance-based correlation analysis, we observed an increase over time in the strength of the correlation between tetracycline ARGs and specific bacterial taxa, including some common human pathogens. In sum, doxy-PEP use over a 6-month period was associated with an increase in the proportion of tetracycline ARGs comprising the gut resistome and an increase in the expression of tetracycline ARGs. At 6 months of doxy-PEP use, no residual differences were observed in alpha and beta diversity or taxonomic composition of the gut microbiome. As doxy-PEP is implemented as a public health strategy, further studies and population-level surveillance of doxycycline-resistant pathogens are needed to understand the implications of these findings. ClinicalTrials.gov registration number: NCT03980223 .

Role of TM7 in the Oral Microbiome and its Implications for Periodontal Disease: A Systematic Review

ABSTRACT Periodontal disease, a prevalent oral health condition, involves a complex microbial community. Advanced sequencing technologies have enabled in-depth studies of the oral microbiome, focusing on specific bacterial taxa like TM7. This systematic review analyzes the role of TM7 in the oral microbiome and its implications for periodontal disease. This review underscores TM7’s importance in the oral microbiome and its potential as a target for future research on periodontal disease pathogenesis.

30 Microbiota and Companion Animal Health

Abstract The intestinal microbiota has been shown to have an important role in health and disease of animals. It is a complex system that depends on interactions between the luminal environment and specific bacterial taxa and their function (e.g., production of short-chain fatty acids, conversion of bile acids). Dietary substrates are an important factor for microbial metabolism and supplements have the potential to help in maintaining intestinal health. Major changes in the microbiota and their loss of function (dysbiosis) are mainly associated with antibiotic treatment and in chronic intestinal disease likely due to chronic remodeling of the epithelium. Therefore, often these changes persist long-term. Chronic enteropathies (CE) occur very commonly in dogs and cats, and are frustrating to treat due to lack of specific markers. The pathophysiology is complex and includes changes in the immune system (e.g., inflammation), intestinal function, and the intestinal microbiome. The current classification based on treatment response (i.e., food- vs. steroid-responsive) is currently being questioned, as new research findings indicate that CE is a syndrome with many overlapping unspecific features, often with chronic irreversible changes in intestinal function and dysbiosis. The presentation will summarize novel research about the pathophysiology and novel concepts in multi-modal therapy to these conditions. This program will help better understand the role of the intestinal microbiota in health and disease (with focus on acute diarrhea and chronic intestinal inflammation). New diagnostic methods for evaluation of the intestinal microbiota will be covered. Finally, this lecture will review how to best manage the clinical signs of acute and chronic diarrhea. This includes new evidence of the negative impact of antibiotics on the microbiome and the critical role nutrition can play in managing these patients.

Redox Homeostasis, Gut Microbiota, and Epigenetics in Neurodegenerative Diseases: A Systematic Review.

Neurodegenerative diseases encompass a spectrum of disorders marked by the progressive degeneration of the structure and function of the nervous system. These conditions, including Parkinson's disease (PD), Alzheimer's disease (AD), Huntington's disease (HD), Amyotrophic lateral sclerosis (ALS), and Multiple sclerosis (MS), often lead to severe cognitive and motor deficits. A critical component of neurodegenerative disease pathologies is the imbalance between pro-oxidant and antioxidant mechanisms, culminating in oxidative stress. The brain's high oxygen consumption and lipid-rich environment make it particularly vulnerable to oxidative damage. Pro-oxidants such as reactive nitrogen species (RNS) and reactive oxygen species (ROS) are continuously generated during normal metabolism, counteracted by enzymatic and non-enzymatic antioxidant defenses. In neurodegenerative diseases, this balance is disrupted, leading to neuronal damage. This systematic review explores the roles of oxidative stress, gut microbiota, and epigenetic modifications in neurodegenerative diseases, aiming to elucidate the interplay between these factors and identify potential therapeutic strategies. We conducted a comprehensive search of articles published in 2024 across major databases, focusing on studies examining the relationships between redox homeostasis, gut microbiota, and epigenetic changes in neurodegeneration. A total of 161 studies were included, comprising clinical trials, observational studies, and experimental research. Our findings reveal that oxidative stress plays a central role in the pathogenesis of neurodegenerative diseases, with gut microbiota composition and epigenetic modifications significantly influencing redox balance. Specific bacterial taxa and epigenetic markers were identified as potential modulators of oxidative stress, suggesting novel avenues for therapeutic intervention. Moreover, recent evidence from human and animal studies supports the emerging concept of targeting redox homeostasis through microbiota and epigenetic therapies. Future research should focus on validating these targets in clinical settings and exploring the potential for personalized medicine strategies based on individual microbiota and epigenetic profiles.

Harnessing the Gut Microbiome: To What Extent Can Pre-/Probiotics Alleviate Immune Activation in Autism Spectrum Disorder?

Children diagnosed with autism spectrum disorder (ASD) are at an increased risk of experiencing gastrointestinal (GI) discomfort, which has been linked to dysfunctions in the microbiome-gut-brain axis. The bidirectional communication between gut and brain plays a crucial role in the overall health of individuals, and alterations in the gut microbiome can contribute to immune activation and gut-brain dysfunction in ASD. Despite the limited and controversial results of pre-/probiotic applications in ASD, this review comprehensively maps the association between ASD clinical symptoms and specific bacterial taxa and evaluates the efficacy of pre-/probiotics in modulating microbiota composition, reducing inflammatory biomarkers, alleviating difficulties in GI distress, sleep problems, core and other ASD-associated symptoms, as well as relieving parental concerns, separately, in individuals with ASD. Beyond simply targeting core ASD symptoms, this review highlights the potential of pre-/probiotic supplementations as a strategy to modulate gut homeostasis and immune response, and to delineate the potential mechanisms by which its direct or mediating effects can alleviate gut-brain dysfunction and poor nutritional status in ASD management. Further well-designed randomized controlled trials are needed to strengthen the existing evidence and establish optimal protocols for the use of pre-/probiotics in the context of ASD.

Root endophytic bacterial communities are shaped by the specific microbiota associated to mycorrhizal symbionts

Abstract Background and aims Arbuscular mycorrhizal fungi (AMF) are beneficial soil microorganisms establishing mutualistic symbioses with most crop plants and promoting plant growth and health. AMF beneficial activities are complemented by their associated microbiota, leading to synergistic interactions positively affecting plant performance. In this work we assessed whether AMF may act as drivers of root bacterial endophytes, facilitating root colonization of host plants by their associated bacteria. Methods Two AMF isolates were used, Funneliformis mosseae from Indiana (USA) and Septoglomus sp. from Tuscany (Italy) in an original experimental microcosm system, utilizing micropropagated plants of Prunus persica x Prunus amygdalus inoculated with either intact or mechanically crushed AMF spores, the former able and the latter unable to establish the symbiosis. Spore and root endophytic bacterial communities diversity were analysed by Illumina Miseq sequencing. Results This study revealed that AMF with their associated bacteria can shape the root endophytic bacterial communities, inducing differential recruitment depending on the composition of spore-associated microbiota. Such data were consistent between two AMF isolates, associated with diverse bacterial communities, as shown by PERMANOVA, Bray Curtis dissimilarity, hierarchical clustering and indicator species analyses. Moreover, specific bacterial taxa were found exclusively in mycorrhizal roots. Our findings suggested also a differential recruitment depending on the ability of AMF to establish mycorrhizal symbioses. Conclusion This work revealed that AMF represent drivers of the endophytic bacterial communities diversity and composition, facilitating root colonization of host plants by their associated bacteria, that become an integral part of the root microbiome as endophytes.

Association Between Gut and Nasal Microbiota and Allergic Rhinitis: A Systematic Review.

Allergic rhinitis is a chronic non-infectious inflammation of the nasal mucosa mediated by specific IgE. Recently, the human microbiome has drawn broad interest as a potential new target for treating this condition. This paper succinctly summarizes the main findings of 17 eligible studies published by February 2024, involving 1044 allergic rhinitis patients and 954 healthy controls from 5 countries. These studies examine differences in the human microbiome across important mucosal interfaces, including the nasal and intestinal areas, between patients and controls. Overall, findings suggest variations in the gut microbiota between allergic rhinitis patients and healthy individuals, although the specific bacterial taxa that significantly changed were not always consistent across studies. Due to the limited scope of existing research and patient coverage, the relationship between the nasal microbiome and allergic rhinitis remains inconclusive. The article discusses the potential immune-regulating role of the gut microbiome in allergic rhinitis. Further well-designed clinical trials with large-scale recruitment of allergic rhinitis patients are encouraged.

Impact of glyphosate on the rhizosphere microbial communities of a double-transgenic maize line D105

Plant roots shape the rhizosphere microbiome, recruiting microbes with beneficial functions. While genetically engineered crops offer yield advantages, their impacts on rhizosphere microbial communities remain understudied. This study evaluated the effects of transgenic maize, alongside a non-transgenic counterpart, on rhizosphere bacterial and fungal community composition using 16S rRNA and ITS amplicon sequencing. Additionally, glyphosate was used to evaluate its impact on microbial assembly and the magnitude of its effect at various maize growth stages. The results showed that transgenic maize D105 line significantly increased bacterial alpha diversity but not fungal diversity. Beta diversity analysis showed clear separation between bacterial and fungal communities at higher glyphosate treatment. Specific bacterial taxa such as Pseudomonas and Sphingomonas were enriched, while fungal taxa such as Ascomycota, Lasiosphaeriaceae, Verticillium were differentially abundant in glyphosate treatments. LEfSe analysis identified distinct enrichment patterns of bacterial (Proteobacteria and Actinobacteria) and fungal taxa (Verticillium and Guehomyces) associated with the transgenic line and glyphosate levels. KEGG functional analysis suggested potential impacts on bacterial metabolic pathways and shifts in fungal trophic modes (saprotrophs, pathogens) within the rhizosphere microbiome. This research provides insights into the classification, functional relationships, and underlying mechanisms shaping microbial communities carrying insect resistance and glyphosate resistance traits.

Exploring the Role of Gut Microbiome in Chronic Inflammatory Diseases: A Comparative Study

Chronic inflammatory diseases, such as inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis, have been increasingly linked to alterations in the gut microbiome. This study aims to explore the role of the gut microbiome in the pathogenesis and progression of chronic inflammatory diseases through a comparative analysis. The research employed a multi-omics approach, integrating metagenomics, metabolomics, and immunological techniques to characterize the gut microbial composition, metabolic profiles, and host-microbiome interactions across different chronic inflammatory conditions. Fecal samples, blood samples, and clinical data were collected from patients diagnosed with inflammatory bowel disease, rheumatoid arthritis, multiple sclerosis, and healthy controls. Bioinformatics and statistical analyses were performed to identify distinct microbial signatures, metabolic pathways, and immune responses associated with each disease state. The findings revealed significant dysbiosis in the gut microbiome of patients with chronic inflammatory diseases, characterized by reduced diversity, altered microbial composition, and disrupted metabolic pathways. Specific bacterial taxa and metabolites were identified as potential biomarkers for disease severity and progression. Additionally, the study highlighted the intricate interplay between the gut microbiome, immune system, and inflammatory processes, providing insights into potential therapeutic targets and personalized interventions. The research concludes that the gut microbiome plays a crucial role in the development and perpetuation of chronic inflammatory diseases, and its modulation through dietary interventions, probiotics, or targeted therapies holds promise for improving disease management and patient outcomes.

Association between gut microbiota and CpG island methylator phenotype in colorectal cancer

ABSTRACT The intestinal microbiota is an important environmental factor implicated in CRC development. Intriguingly, modulation of DNA methylation by gut microbiota has been reported in preclinical models, although the relationship between tumor-infiltrating bacteria and CIMP status is currently unexplored. In this study, we investigated tumor-associated bacteria in 203 CRC tumor cases and validated the findings using The Cancer Genome Atlas datasets. We assessed the abundance of Bacteroides fragilis, Escherichia coli, Fusobacterium nucleatum, and Klebsiella pneumoniae through qPCR analysis and observed enrichment of all four bacterial species in CRC samples. Notably, except for E. coli, all exhibited significant enrichment in cases of CIMP. This enrichment was primarily driven by a subset of cases distinguished by high levels of these bacteria, which we labeled as “Superhigh”. The bacterial Superhigh status showed a significant association with CIMP (odds ratio 3.1, p-value = 0.013) and with MLH1 methylation (odds ratio 4.2, p-value = 0.0025). In TCGA CRC cases (393 tumor and 45 adj. normal), bacterial taxa information was extracted from non-human whole exome sequencing reads, and the bacterial Superhigh status was similarly associated with CIMP (odds ratio 2.9, p < 0.001) and MLH1 methylation (odds ratio 3.5, p < 0.001). Finally, 16S ribosomal RNA gene sequencing revealed high enrichment of Bergeyella spp. C. concisus, and F. canifelinum in CIMP-Positive tumor cases. Our findings highlight that specific bacterial taxa may influence DNA methylation, particularly in CpG islands, and contribute to the development and progression of CIMP in colorectal cancer.

Chronic endometritis and the endometrial microbiota: implications for reproductive success in patients with recurrent implantation failure

BackgroundChronic endometritis (CE) is associated with poor reproductive outcomes, yet the role of endometrial microbiota in patients with recurrent implantation failure (RIF) and CE remains unclear. This study aims to characterize endometrial microbiota in RIF patients with CE and assess its implications for reproductive outcomes.MethodsIn this prospective study, we enrolled RIF patients both with and without CE. Endometrial and cervical samples were collected for 16 S rRNA gene sequencing. Microbiota composition was compared between groups using diversity indices, phylum, and genus-level analysis. Canonical correlation analysis (CCA) and Spearman’s correlation coefficients were used to assess relationships between CE, reproductive outcomes, and microbiota. Predictive functional profiling was performed to evaluate metabolic pathways associated with CE.ResultsEndometrial microbiota in CE patients exhibited greater diversity and evenness compared to non-CE patients. Principal coordinates analysis (PCoA) revealed distinct clustering between CE and non-CE groups. Linear discriminant analysis (LDA) identified Proteobacteria, Aminicenantales, and Chloroflexaceae as characteristic of CE, while Lactobacillus, Acinetobacter, Herbaspirillum, Ralstonia, Shewanela, and Micrococcaceae were associated with non-CE. CCA demonstrated associations between CE, adverse reproductive outcomes, and specific bacterial taxa. Microbial metabolic pathways significantly differed between CE and non-CE groups, with enrichment in pathways related to cofactors, vitamins, secondary metabolites, and the immune system in CE patients.ConclusionRIF patients with CE exhibit distinct endometrial microbiota compositions associated with adverse reproductive outcomes. The increased microbial diversity and altered metabolic pathways in CE suggest a potential correlation with reproductive outcomes, although further studies are necessary to elucidate the causal relationship between microbiota alterations and fertility. Modulating the endometrial microbiome may represent a novel therapeutic strategy to improve IVF outcomes in patients with CE.

High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats

Obesity, associated with the intake of a high-fat diet (HFD), and anxiety are common among those living in modern urban societies. Recent studies suggest a role of microbiome-gut-brain axis signaling, including a role for brain serotonergic systems in the relationship between HFD and anxiety. Evidence suggests the gut microbiome and the serotonergic brain system together may play an important role in this response. Here we conducted a nine-week HFD protocol in male rats, followed by an analysis of the gut microbiome diversity and community composition, brainstem serotonergic gene expression (tph2, htr1a, and slc6a4), and anxiety-related defensive behavioral responses. We show that HFD intake decreased alpha diversity and altered the community composition of the gut microbiome in association with obesity, increased brainstem tph2, htr1a and slc6a4 mRNA expression, including in the caudal part of the dorsomedial dorsal raphe nucleus (cDRD), a subregion previously associated with stress- and anxiety-related behavioral responses, and, finally, increased anxiety-related defensive behavioral responses. The HFD increased the Firmicutes/Bacteroidetes ratio relative to control diet, as well as higher relative abundances of Blautia, and decreases in Prevotella. We found that tph2, htr1a and slc6a4 mRNA expression were increased in subregions of the dorsal raphe nucleus in the HFD, relative to control diet. Specific bacterial taxa were associated with increased serotonergic gene expression in the cDRD. Thus, we propose that HFD-induced obesity is associated with altered microbiome-gut-serotonergic brain axis signaling, leading to increased anxiety-related defensive behavioral responses in rats.

Comparative analysis of endometrial, vaginal, and gut microbiota in patients with and without adenomyosis.

Alterations in microbiota composition have been implicated in a variety of human diseases. Patients with adenomyosis present immune dysregulation leading to a persistent chronic inflammatory response. In this context, the hypothesis that alterations in the microbiota may be involved in the pathogenesis of adenomyosis, by affecting the epigenetic, immunologic, and biochemical functions of the host, has recently been postulated. The aim of the present study was to compare the microbiota composition in the vagina, endometrium, and gut of individuals with and without adenomyosis. Cross-sectional study including 38 adenomyosis patients and 46 controls, performed between September 2021 and October 2022 in a university hospital-based research center. The diagnosis of adenomyosis was based on sonographic criteria. Fecal, vaginal, and endometrial samples were collected. Study of the microbiota using 16S rRNA gene sequencing. Patients with adenomyosis exhibited a significant reduction in the gut microbial alpha diversity compared with healthy controls (Chao1 p = 0.012, Fisher p = 0.005, Observed species p = 0.005). Beta-diversity analysis showed significant differences in the compositions of both gut and vaginal microbiota between adenomyosis patients and the control group (Adonis p-value = 0.001; R2 = 0.03 and Adonis p-value = 0.034; R2 = 0.04 respectively). Specific bacterial taxa were found to be either overrepresented (Rhodospirillales, Ruminococcus gauvreauii group, Ruminococcaceae, and Actinomyces) or underrepresented in the gut and endometrial microbiota of adenomyosis patients compared with controls. Distinct microbiota profiles were identified among patients with internal and external adenomyosis phenotypes. The study revealed reduced gut microbiota diversity in adenomyosis patients, accompanied by distinct compositions in gut and vaginal microbiota compared with controls. Overrepresented or underrepresented bacterial taxa were noted in the gut and endometrial microbiota of adenomyosis patients, with variations in microbiota profiles among those with internal and external adenomyosis phenotypes. These findings suggest a potential association between microbiota and adenomyosis, indicating the need for further research to comprehensively understand the implications of these differences.

Characteristics of cervicovaginal microflora at different cervical maturity during late pregnancy: A nested case-control study.

The mechanism of cervical ripening in late pregnancy is still unclear. The vaginal microbiome has been reported to correlate with the preterm birth and short cervix in pregnant women. However, the associations between the cervical maturity and the vaginal microbiome are still poorly understood. We aim to analyze the cervicovaginal microflora in women with ripe cervix and in those who are unripe when delivering at term. Cervicovaginal swabs were collected between 40 and 41 weeks of gestation from the following 2 different groups of patients: ripe group (n = 25) and unripe group (n = 25). Samples were tested using 16S ribosomal RNA gene high-throughput sequencing and analyzed by bioinformatics platform. This study highlights the relationship between cervical maturity during late pregnancy and the composition of the cervicovaginal microflora. Both α- and β-diversity analyses demonstrated significant differences between women with a ripe cervix and those with an unripe cervix. Notably, the Lactobacillus profile was found to be closely linked to cervical maturity. There was a significant difference in the vaginal community state type, with CST IV being more prevalent in women with an unripe cervix. Furthermore, the association between CST IV and the unripe cervix group, as indicated by the odds ratio of 8.6, underscores its relevance in evaluating cervical maturity, when compared to other Lactobacillus-dominant community state types. Additionally, several bacterial taxa, particularly Lactobacillus, exhibited differential relative abundances between the two groups. This study provided significant evidence regarding the relationship between the vaginal microbiome and cervical maturity, highlighting the differential diversity, community state types, and specific bacterial taxa, such as Lactobacillus, that are associated with cervical maturation status. These findings contributed to our understanding of the dynamics of the cervicovaginal microflora during late pregnancy and its implications for cervical health.