-
Reproductive Sciences (Thousand Oaks,... Jul 2024Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility.... (Meta-Analysis)
Meta-Analysis Review
Polycystic ovary syndrome (PCOS) is a prevalent endocrine and metabolic disorder that is frequently linked to anovulation in women who are experiencing infertility. Intestinal flora, also known as the "second genome" of the host, is closely associated with chronic metabolic diseases. Recently, there has been increasing attention on the connection between PCOS and the gut microbiome, and experiments have been conducted. However, the results were unsatisfactory and inconsistent. This review aims to provide a comprehensive overview of the literature investigating the associations between the gut microbiome and PCOS in adults. The goal is to identify whether there are changes in the composition of the gut microbiome in individuals with PCOS. This is the first systematic review to focus on functional alterations in the gut microbiome, which could provide insights into potential mechanisms of microbial involvement in the development of PCOS. We found that there was no significant change in gut microbiome biodiversity in PCOS. Meta-analyses of three studies revealed a significantly higher abundance of Proteobacteria (1.12, 95% CI, 0.21, 2.02, I = 0%) in adults with PCOS. At the genus level, Bacteroides, Enterococcus, and Escherichia-Shigella were found to be enriched in patients with PCOS. Species such as Ruminococcus gnavus group, Parabacteroides distasonis, and Bacteroides fragilis showed an increase in PCOS. Metabolic pathways associated with glucose, lipid metabolism, bile acid metabolism, and protein absorption were found to be enriched in individuals with PCOS. The gut microbiome in PCOS is not characterized by lower diversity, but the composition is altered at the phylum, family, genus, or species level. Consequently, the metabolic pathway differs according to the phenotype of PCOS.
Topics: Polycystic Ovary Syndrome; Humans; Gastrointestinal Microbiome; Female; Adult; Observational Studies as Topic
PubMed: 38212581
DOI: 10.1007/s43032-023-01440-4 -
Frontiers in Microbiology 2023Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced...
INTRODUCTION
Contusion type of traumatic brain injury (TBI) is a major cause of locomotor disability and mortality worldwide. While post-TBI deleterious consequences are influenced by gender and gut dysbiosis, the sex-specific importance of commensal gut microbiota is underexplored after TBI. In this study, we investigated the impact of controlled cortical impact (CCI) injury on gut microbiota signature in a sex-specific manner in mice.
METHODS
We depleted the gut microflora of male and female C57BL/6 mice using antibiotic treatment. Thereafter, male mice were colonized by the gut microbiota of female mice and vice versa, employing the fecal microbiota transplantation (FMT) method. CCI surgery was executed using a stereotaxic impactor (Impact One™). For the 16S rRNA gene amplicon study, fecal boli of mice were collected at 3 days post-CCI (dpi).
RESULTS AND DISCUSSION
CCI-operated male and female mice exhibited a significant alteration in the genera of , , . At the species level, less abundance of and was observed in female mice, implicating the importance of sex-specific bacteriotherapy in CCI-induced neurological deficits. FMT from female donor mice to male mice displayed an increase in genera of , , and and species of and . Female FMT-recipient mice from male donors showed an upsurge in the genus and species of , , and . These results suggest that the post-CCI neurological complications may be influenced by the differential gut microbiota perturbation in male and female mice.
PubMed: 38410824
DOI: 10.3389/fmicb.2023.1336537 -
Frontiers in Endocrinology 2024This study sought to elucidate the causal association between gut microbiota (GM) composition and type 2 diabetes mellitus (T2DM) through a comprehensive two-sample...
OBJECTIVE
This study sought to elucidate the causal association between gut microbiota (GM) composition and type 2 diabetes mellitus (T2DM) through a comprehensive two-sample bidirectional Mendelian randomization analysis.
METHOD
T2DM data were sourced from the IEU OpenGWAS Project database, complemented by 211 gut microbiota (GM) datasets from the MiBioGen Federation. The primary analytical approach employed was inverse variance weighted (IVW), supplemented by MR-Egger regression and weighted median (WME) methods to investigate their potential interplay. Results were assessed using odds ratios () and 95% confidence intervals (). The robustness and reliability of the findings were confirmed through leave-one-out analysis, heterogeneity testing, and assessment of horizontal pleiotropy. Furthermore, we explored the potential mediating role of metabolites in the pathway linking GM to T2DM.
RESULT
A set of 11 Single Nucleotide Polymorphisms (SNPs) linked to GM were identified as instrumental variables (IVs). The IVW analysis revealed that increased abundance of the , and corresponded to a heightened risk of T2DM. Conversely, higher levels of , and were associated with a reduced risk of T2DM. However, following false discovery rate (FDR) correction, only the abundance of genus Lachnoclostridium retained a significant positive correlation with T2DM risk ( = 1.22, = 0.09), while the other ten GM showed suggestive associations with T2DM. Reverse MR analysis did not reveal any causal relationship between T2DM and the increased risk associated with the identified GM. Additionally, metabolites did not exhibit mediating effects in this context.
CONCLUSION
This study effectively pinpointed specific GM associated with T2DM, potentially paving the way for novel biomarkers in the prevention and treatment of this condition. The findings suggested that probiotics could emerge as a promising avenue for managing T2DM in the future. Furthermore, the analysis indicated that metabolites do not appear to act as mediators in the pathway from GM to T2DM.
Topics: Humans; Gastrointestinal Microbiome; Diabetes Mellitus, Type 2; Mendelian Randomization Analysis; Reproducibility of Results; Databases, Factual
PubMed: 38495787
DOI: 10.3389/fendo.2024.1313651 -
IScience Sep 2023In a scenario where the discovery of new molecules to fight antibiotic resistance is a public health concern, ribosomally synthesized and post-translationally modified...
In a scenario where the discovery of new molecules to fight antibiotic resistance is a public health concern, ribosomally synthesized and post-translationally modified peptides constitute a promising alternative. In this context, the Gram-positive human gut symbiont E1 produces five sactipeptides, Ruminococcins C1 to C5 (RumC1-C5), co-expressed with two radical SAM maturases. RumC1 has been shown to be effective against various multidrug resistant Gram-positives clinical isolates. Here, after adapting the biosynthesis protocol to obtain the four mature RumC2-5 we then evaluate their antibacterial activities. Establishing first that both maturases exhibit substrate tolerance, we then observed a variation in the antibacterial efficacy between the five isoforms. We established that all RumCs are safe for humans with interesting multifunctionalities. While no synergies where observed for the five RumCs, we found a synergistic action with conventional antibiotics targeting the cell wall. Finally, we identified crucial residues for antibacterial activity of RumC isoforms.
PubMed: 37664601
DOI: 10.1016/j.isci.2023.107563 -
International Immunopharmacology Apr 2024Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively...
BACKGROUND
Dupilumab has demonstrate its potential to orchestrate inflammatory skin microenvironment, enhance skin barrier and shift skin microbiome dysbiosis, collectively contributing to clinical improvement in patients with atopic dermatitis (AD). As the second genome of human body, growing evidence suggests that the gut microbiome might relate to the host response to treatments. Little is known about the association between dupilumab treatment and gut microbiome in AD patients.
OBJECTIVE
We aimed to characterize the gut microbiome among Chinese subjects with or without AD and determine the potential effect of dupilumab on the gut microbiome.
RESULTS
The 16 s rRNA gene sequencing was conducted on 48 healthy controls (HC), 44 AD patients and 27 AD patients who received dupilumab for 16 weeks. Prior to treatment, we identified the changed beta-diversity, increased Firmicutes/Bacteroidetes ratio, decreased Bifidobacterium and expanded Faecalibacterium among the AD patients compared to HC. After 16 weeks of dupilumab treatment, gut microbiome dysbiosis of the AD patients improved with reversed beta-diversity, closer bacterial connections, increased colonization of Bifidobacterium, Ruminococcus gnavus, and Coprococcus, which were negatively correlated with disease severity indicators. This shift was largely independent of the degree of clinical improvement. Bacterial function analysis revealed further metabolic alterations following dupilumab treatment, including up-regulated expression of genes involved in the indole pathway of tryptophan metabolism, corroborated by quantitative UHPLC-MS/MS analysis.
CONCLUSION
Dupilumab treatment tends to help shift the gut microbial dysbiosis in AD patients to a healthier state, along with improved intestinal tryptophan metabolism, suggesting the gut flora and its metabolites may mediate part of the synergistic therapeutic effects on the host.
Topics: Humans; Dermatitis, Atopic; Gastrointestinal Microbiome; Tryptophan; Dysbiosis; Tandem Mass Spectrometry; China; Antibodies, Monoclonal, Humanized
PubMed: 38493690
DOI: 10.1016/j.intimp.2024.111867 -
Journal of Ethnopharmacology Sep 2024Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of...
ETHNOPHARMACOLOGICAL RELEVANCE
Da-Jian-Zhong decoction (DJZD) is a herbal formula clinically used for abdominal pain and diarrhea induced by spleen-Yang deficiency syndrome. Recently, treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with DJZD has received increasing attention, but the underlying mechanism of action remains elusive.
AIM OF THE STUDY
We aimed to evaluate the therapeutic effect of DJZD on IBS-D rats and to elucidate the underlying mechanisms.
MATERIALS AND METHODS
An IBS-D rats model was constructed using a two-factor superposition method of neonatal maternal separation and Senna folium aqueous extract lavage. Moreover, the effect of DJZD was evaluated based on the body weight, rectal temperature, abdominal withdrawal reflex (AWR), and Bristol stool scale score (BSS). The factors that regulate the DJZD effects on IBS-D were estimated using whole microbial genome, transcriptome sequencing (RNA-Seq), flow cytometry, and quantitative reverse transcription polymerase chain reaction (RT-qPCR) analyses.
RESULTS
We found that DJZD alleviated the symptoms of IBS-D rats, with the low-dose (2.4 g/kg) as the better ones, as shown by the higher body weight and lower AWR score and BSS. At the phylum level, the relative abundance of Bacteroidetes was obviously increased, and at the genus level, Lactobacillus and Parabacteroides were increased, while that of Firmicutes_bacterium_424 and Ruminococcus gnavus was decreased in DJZD group. Furthermore, the significantly enriched GO terms after treatment with DJZD mainly included the immune response, positive regulation of activated T cell proliferation, and positive regulation of interleukin-17 (IL-17) production. Importantly, flow cytometry analysis further revealed that the T helper cell type 17/regulatory T cell (Th17/Treg) balance contributed to the DJZD-induced alleviation of IBS-D symptoms, as DJZD downregulated Th17/Treg ratio and Th17 cell-related cytokines IL-17 and IL-6 levels in the colon.
CONCLUSIONS
These results demonstrated that DJZD has a good therapeutic effect on IBS-D rats, probably by maintaining the homeostasis of gut microbiota and regulating Th17/Treg balance and its related inflammatory factors.
Topics: Animals; Irritable Bowel Syndrome; Gastrointestinal Microbiome; Drugs, Chinese Herbal; Diarrhea; Th17 Cells; Rats, Sprague-Dawley; Male; T-Lymphocytes, Regulatory; Rats; Disease Models, Animal; Female
PubMed: 38729534
DOI: 10.1016/j.jep.2024.118275 -
Journal of Microbiology and... Dec 2023This study aimed to evaluate the effects of and isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db...
This study aimed to evaluate the effects of and isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of and , which were significantly increased in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the _NK4A136_group, , , , and . Untargeted metabolomics analysis showed that lotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that and _group were negatively correlated with 5-hydroxyindoleacetic acid and 13(S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of and to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.
Topics: Humans; Animals; Mice; Lactobacillaceae; Gastrointestinal Microbiome; Inulin; Tryptophan; Diabetes Mellitus, Type 2; Hydroxyindoleacetic Acid; RNA, Ribosomal, 16S; Metabolome; Linoleic Acids
PubMed: 37734909
DOI: 10.4014/jmb.2304.04039 -
BioRxiv : the Preprint Server For... Jul 2023Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with...
UNLABELLED
Chronic intestinal inflammation is a poorly understood manifestation of Cystic Fibrosis (CF), which may be refractory to ion channel CFTR modulator therapy. People with CF exhibit intestinal dysbiosis which has potential for stimulating intestinal and systemic inflammation. CFTR is expressed in organ epithelia and in the leukocyte population. Here, we investigate the contribution of intestinal epithelial-specific loss of Cftr (iCftr KO) to dysbiosis and inflammation in mice treated with either of two anti-obstructive dietary regimens necessary to maintain CF mouse models (PEG laxative or a liquid diet, LiqD). Feces collected from iCftr KO mice and their wildtype (WT) sex-matched littermates were used to measure fecal calprotectin and to perform 16S rRNA sequencing to characterize the gut microbiome. Fecal calprotectin was elevated in iCftr KO relative to WT samples of mice consuming either PEG or LiqD. PEG iCftr KO mice did not show a change in α-diversity versus WT but demonstrated a significant difference in microbial composition (β-diversity) with increases in phylum , family , four genera of including , and mucolytic genus . Fecal microbiome analysis of LiqD iCftr KO mice showed both decreased α-diversity and differences in microbial composition with increases in family , families and , and enrichment of , , , mucolytic , and reduction of . It was concluded that epithelial-specific loss of Cftr is a major driver of CF intestinal dysbiosis and inflammation with significant similarities to previous studies of global Cftr KO mice.
NEW AND NOTEWORTHY
Chronic intestinal inflammation is a manifestation of cystic fibrosis (CF), a disease caused by loss of the anion channel CFTR that is expressed in many tissues. This study shows that intestinal epithelial cell-specific loss of CFTR (iCftr KO) in mice is sufficient to induce intestinal dysbiosis and inflammation. Studies were performed on mice consuming either dietary regimen (PEG laxative or liquid diet) routinely used to prevent obstruction in CF mice.
PubMed: 37546931
DOI: 10.1101/2023.07.24.550378 -
Oral Oncology Jan 2024Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut...
OBJECTIVES
Chemoradiation (CRT) in patients with locally advanced head and neck squamous cell cancer (HNSCC) is associated with significant toxicities, including mucositis. The gut microbiome represents an emerging hallmark of cancer and a potentially important biomarker for CRT-related adverse events. This prospective study investigated the association between the gut microbiome composition and CRT-related toxicities in patients with HNSCC, including mucositis.
MATERIALS AND METHODS
Stool samples from patients diagnosed with locally advanced HNSCC were prospectively collected prior to CRT initiation and analyzed using shotgun metagenomic sequencing to evaluate gut microbiome composition at baseline. Concurrently, clinicopathologic data, survival outcomes and the incidence and grading of CRT-emergent adverse events were documented in all patients.
RESULTS
A total of 52 patients were included, of whom 47 had baseline stool samples available for metagenomic analysis. Median age was 62, 83 % patients were men and 54 % had stage III-IV disease. All patients developed CRT-induced mucositis, including 42 % with severe events (i.e. CTCAE v5.0 grade ≥ 3) and 25 % who required enteral feeding. With a median follow-up of 26.5 months, patients with severe mucositis had shorter overall survival (HR = 3.3, 95 %CI 1.0-10.6; p = 0.02) and numerically shorter progression-free survival (HR = 2.8, 95 %CI, 0.8-9.6; p = 0.09). The gut microbiome beta-diversity of patients with severe mucositis differed from patients with grades 1-2 mucositis (p = 0.04), with enrichment in Mediterraneibacter (Ruminococcus gnavus) and Clostridiaceae family members, including Hungatella hathewayi. Grade 1-2 mucositis was associated with enrichment in Eubacterium rectale, Alistipes putredinis and Ruminococcaceae family members. Similar bacterial profiles were observed in patients who required enteral feeding.
CONCLUSION
Patients who developed severe mucositis had decreased survival and enrichment in specific bacteria associated with mucosal inflammation. Interestingly, these same bacteria have been linked to immune checkpoint inhibitor resistance.
Topics: Male; Humans; Female; Squamous Cell Carcinoma of Head and Neck; Head and Neck Neoplasms; Mucositis; Prospective Studies; Gastrointestinal Microbiome; Chemoradiotherapy
PubMed: 38006691
DOI: 10.1016/j.oraloncology.2023.106623 -
Frontiers in Nutrition 2023Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects...
Dietary fiber improves intestinal environments, by, among others, increasing stool frequency. Kale is a good source of dietary fiber and minerals; however, the effects of kale on the intestinal environment have not yet been evaluated. This study determined how the intestinal environment, including the intestinal microbiota and its metabolome, and stool frequency are affected by the consumption of kale, in humans. A randomized controlled crossover trial, with a 4-week consumption of kale or control food, was conducted. An integrated analysis of the intestinal microbiota and metabolome was performed, and their relationship with improvements in stool frequency was analyzed. Kale intake for 4 weeks significantly increased stool frequency and altered some intestinal microbes, such as an increase in the [] group and a decrease in the [] group. Analysis of subjects with increased stool frequency revealed that this group had smaller amounts of stool before kale intake. Our findings indicate that kale modifies certain gut microbes, such as [] and [] , and improves bowel movements, particularly in those with smaller stool amounts.
PubMed: 38094924
DOI: 10.3389/fnut.2023.1247683