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Nature Communications Nov 2023The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly...
The gut microbiota may have an effect on the therapeutic resistance and toxicity of immune checkpoint inhibitors (ICIs). However, the associations between the highly variable genomes of gut bacteria and the effectiveness of ICIs remain unclear, despite the fact that merely a few gene mutations between similar bacterial strains may cause significant phenotypic variations. Here, using datasets from the gut microbiome of 996 patients from seven clinical trials, we systematically identify microbial genomic structural variants (SVs) using SGV-Finder. The associations between SVs and response, progression-free survival, overall survival, and immune-related adverse events are systematically explored by metagenome-wide association analysis and replicated in different cohorts. Associated SVs are located in multiple species, including Akkermansia muciniphila, Dorea formicigenerans, and Bacteroides caccae. We find genes that encode enzymes that participate in glucose metabolism be harbored in these associated regions. This work uncovers a nascent layer of gut microbiome heterogeneity that is correlated with hosts' prognosis following ICI treatment and represents an advance in our knowledge of the intricate relationships between microbiota and tumor immunotherapy.
Topics: Humans; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Microbiota; Metagenome; Bacteria; Neoplasms
PubMed: 37973916
DOI: 10.1038/s41467-023-42997-7 -
Nutrients Nov 2023The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization...
The objective of this study was to examine the correlation between gut microbiota and both age-related macular degeneration (AMD) and glaucoma. Mendelian randomization studies were conducted utilizing the data sourced from the genome-wide association study (GWAS) database for the gut microbiome, AMD, and glaucoma. Single nucleotide polymorphism (SNP) estimates were summarized through five Mendelian randomization (MR) methods. We utilized Cochran's Q statistic to evaluate the heterogeneity of the instrumental variables (IVs). Additionally, we employed a "leave-one-out" approach to verify the stability of our findings. Inverse variance weighted (IVW) suggests that Eubacterium (oxidoreducens group) and Parabacteroides had a protective effect on AMD. Both weighted median and IVW suggest that Lachnospiraceae (NK4A136 group) and Ruminococcaceae (UCG009) had a protective effect on AMD. However, both weighted median and IVW suggest that Dorea had a risk effect on AMD. Similarly, The IVW of Eubacterium (ventriosum group) showed a risk effect on AMD. The weighted median of Eubacterium (nodatum group), Lachnospiraceae (NC2004 group), and Roseburia had a risk effect on glaucoma. IVW suggested that Ruminococcaceae (UCG004) had a risk effect on glaucoma. Reverse MR analysis found a causal link between Eubacterium (nodatum group) and glaucoma. No causal relationships were found between AMD or glaucoma and the other mentioned bacterial groups. No significant heterogeneity or evidence of horizontal pleiotropy was detected. This study found that certain gut bacteria had protective effects on AMD, while others may be risk factors for AMD or glaucoma. Likewise, reverse MR found that glaucoma led to an increased abundance of certain gut bacteria. Further trials are needed to clarify the specific mechanisms involved.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Glaucoma; Macular Degeneration; Clostridiales; Lactobacillales
PubMed: 37960299
DOI: 10.3390/nu15214646 -
Gut Pathogens Nov 2023Gut microbiota is pivotal in maintaining children's health and well-being. The ingestion of enteric pathogens and dysbiosis lead to Environmental Enteric Dysfunction...
BACKGROUND
Gut microbiota is pivotal in maintaining children's health and well-being. The ingestion of enteric pathogens and dysbiosis lead to Environmental Enteric Dysfunction (EED), which is essential in stunting pathogenesis. The roles of gut microbiome and enteric infections have not been explored comprehensively in relation to childhood stunting in Indonesia. This study aimed to determine the correlation between gut microbiota composition, enteric infections, and growth biomarker, Insulin-like Growth Factor 1 (IGF-1), in stunted children from Pidie, Aceh, Indonesia.
METHODS
This study was a case-control study involving 42 subjects aged 24 to 59 months, comprising 21 stunted children for the case and 21 normal children for the control group. The IGF-1 serum level was quantified using ELISA. The gut microbiome profiling was conducted using 16S rDNA amplicon sequencing. The expression of enteric pathogens virulence genes was determined using quantitative PCR (qPCR) assay. The correlations of observed variables were analysed using suitable statistical analyses.
RESULTS
The result showed that the IGF-1 sera levels in stunted were lower than those in normal children (p ≤ 0.001). The abundance of Firmicutes (50%) was higher than Bacteroidetes (34%) in stunted children. The gut microbiome profile of stunted children showed enriched genera such as Blautia, Dorea, Collinsella, Streptococcus, Clostridium sensu stricto 13, Asteroleplasma and Anaerostipes. Meanwhile the depleted genera comprised Prevotella, Lactococcus, Butyrivibrio, Muribaculaceae, Alloprevotella, Akkermansia, Enterococcus, Terrisporobacter and Turicibacter. The abundance of water biological contaminants such as Aeromonas, Stappiaceae, and Synechococcus was also higher in stunted children compared to normal children. The virulence genes expression of Enteroaggregative Escherichia coli (aaiC), Enterotoxigenic E. coli (estA), Enteropathogenic E. coli (eaeA), Shigella/Enteroinvasive E. coli (ipaH3) and Salmonella enterica (ompC) in stunted was higher than in normal children (p ≤ 0.001), which negatively correlated to height and level of IGF-1.
CONCLUSION
The present study showed the distinctive gut microbiome profile of stunted and normal children from Pidie, Aceh, Indonesia. The gut microbiota of stunted children revealed dysbiosis, comprised several pro-inflammatory, metabolic abnormalities and high-fat/low-fiber diet-related taxa, and expressed virulence genes of enteric pathogens. These findings provide evidence that it is imperative to restore dysbiosis and preserve the balance of gut microbiota to support linear growth in children.
PubMed: 37946290
DOI: 10.1186/s13099-023-00581-w -
Gut Microbes Dec 2023adapts to the host environment by altering gene expression. Because of the complexity of the gut microbiome, current transcriptome studies have focused on...
adapts to the host environment by altering gene expression. Because of the complexity of the gut microbiome, current transcriptome studies have focused on microbiota-undeveloped conditions, neglecting the interaction between the host's commensal gut microbiota and . In this study, we analyzed the transcriptome of fully colonized adult mice using coated-magnetic chitin beads (vcMCB). This provides a simple yet powerful method for obtaining high-quality RNA from during colonization in mice. The transcriptome of recovered from adult mice infected with vcMCB shows differential expression of several genes when compared to recovered from the infant mouse and infant rabbit model. Some of these genes were also observed to be differentially expressed in previous studies of recovered from human infection when compared to grown . In particular, we confirmed that resists the inhibitory effects of low pH and formic acid from gut microbiota, such as and , by downregulating . We propose that the product may protect from formic acid stress through a novel acid tolerance response mechanism. Transcriptomic data obtained using the vcMCB system provide new perspectives on the interaction between and the gut microbiota, and this approach can also be applied to studies of other pathogenic bacteria.
Topics: Adult; Animals; Humans; Mice; Rabbits; Vibrio cholerae; Gastrointestinal Microbiome; Transcriptome; Chitin; Cholera; Magnetic Phenomena
PubMed: 37934002
DOI: 10.1080/19490976.2023.2274125 -
International Journal of Molecular... Oct 2023Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing...
Non-alcoholic fatty liver disease (NAFLD) is considered the most common chronic liver disease worldwide, affecting nearly 25% of the global adult population. Increasing evidence suggests that functional and compositional changes in the gut microbiota may contribute to the development and promote the progression of NAFLD. 16S rRNA gene next-generation sequencing is widely used to determine specific features of the NAFLD microbiome, but a complex system such as the gut microbiota requires a comprehensive approach. We used three different approaches: MALDI-TOF-MS of bacterial cultures, qPCR, and 16S NGS sequencing, as well as a wide variety of statistical methods to assess the differences in gut microbiota composition between NAFLD patients without significant fibrosis and the control group. The listed methods showed enrichment in sp. and for the control samples and enrichment in (and in particular sp.) and in NAFLD. The families, , , and (particularly and ), were also found to be important taxa for NAFLD microbiome evaluation. Considering individual method observations, an increase in and a decrease in for NAFLD patients were detected using MALDI-TOF-MS. An increase in , , , , , and , and a decrease in in NAFLD were observed with 16S NGS, and enrichment in was shown using qPCR analysis. These findings confirm that NAFLD is associated with changes in gut microbiota composition. Further investigations are required to determine the cause-and-effect relationships and the impact of microbiota-derived compounds on the development and progression of NAFLD.
Topics: Adult; Humans; Non-alcoholic Fatty Liver Disease; Gastrointestinal Microbiome; RNA, Ribosomal, 16S; Fibrosis; Microbiota; Bacteroidetes; Liver
PubMed: 37894951
DOI: 10.3390/ijms242015272 -
Scientific Reports Oct 2023Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis...
Uncovering the relationship between gut microbial dysbiosis, metabolomics, and dietary intake in type 2 diabetes mellitus and in healthy volunteers: a multi-omics analysis.
Type 2 Diabetes Mellitus has reached epidemic levels globally, and several studies have confirmed a link between gut microbial dysbiosis and aberrant glucose homeostasis among people with diabetes. While the assumption is that abnormal metabolomic signatures would often accompany microbial dysbiosis, the connection remains largely unknown. In this study, we investigated how diet changed the gut bacteriome, mycobiome and metabolome in people with and without type 2 Diabetes.1 Differential abundance testing determined that the metabolites Propionate, U8, and 2-Hydroxybutyrate were significantly lower, and 3-Hydroxyphenyl acetate was higher in the high fiber diet compared to low fiber diet in the healthy control group. Next, using multi-omics factor analysis (MOFA2), we attempted to uncover sources of variability that drive each of the different groups (bacterial, fungal, and metabolite) on all samples combined (control and DM II). Performing variance decomposition, ten latent factors were identified, and then each latent factor was tested for significant correlations with age, BMI, diet, and gender. Latent Factor1 was the most significantly correlated. Remarkably, the model revealed that the mycobiome explained most of the variance in the DM II group (12.5%) whereas bacteria explained most of the variance in the control group (64.2% vs. 10.4% in the DM II group). The latent Factor1 was significantly correlated with dietary intake (q < 0.01). Further analyses of the impact of bacterial and fungal genera on Factor1 determined that the nine bacterial genera (Phocaeicola, Ligilactobacillus, Mesosutterella, Acidaminococcus, Dorea A, CAG-317, Caecibacter, Prevotella and Gemmiger) and one fungal genus (Malassezia furfur) were found to have high factor weights (absolute weight > 0.6). Alternatively, a linear regression model was fitted per disease group for each genus to visualize the relationship between the factor values and feature abundances, showing Xylose with positive weights and Propionate, U8, and 2-Hydroxybutyrate with negative weights. This data provides new information on the microbially derived changes that influence metabolic phenotypes in response to different diets and disease conditions in humans.
Topics: Humans; Diabetes Mellitus, Type 2; Gastrointestinal Microbiome; Dysbiosis; Propionates; Multiomics; Metabolomics; Bacteria; Eating; Hydroxybutyrates
PubMed: 37863978
DOI: 10.1038/s41598-023-45066-7 -
Genome Biology Oct 2023The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to...
BACKGROUND
The gut microbiota plays a crucial role in regulating host metabolism and producing uremic toxins in patients with end-stage renal disease (ESRD). Our objective is to advance toward a holistic understanding of the gut ecosystem and its functional capacity in such patients, which is still lacking.
RESULTS
Herein, we explore the gut microbiome of 378 hemodialytic ESRD patients and 290 healthy volunteers from two independent cohorts via deep metagenomic sequencing and metagenome-assembled-genome-based characterization of their feces. Our findings reveal fundamental alterations in the ESRD microbiome, characterized by a panel of 348 differentially abundant species, including ESRD-elevated representatives of Blautia spp., Dorea spp., and Eggerthellaceae, and ESRD-depleted Prevotella and Roseburia species. Through functional annotation of the ESRD-associated species, we uncover various taxon-specific functions linked to the disease, such as antimicrobial resistance, aromatic compound degradation, and biosynthesis of small bioactive molecules. Additionally, we show that the gut microbial composition can be utilized to predict serum uremic toxin concentrations, and based on this, we identify the key toxin-contributing species. Furthermore, our investigation extended to 47 additional non-dialyzed chronic kidney disease (CKD) patients, revealing a significant correlation between the abundance of ESRD-associated microbial signatures and CKD progression.
CONCLUSION
This study delineates the taxonomic and functional landscapes and biomarkers of the ESRD microbiome. Understanding the role of gut microbiota in ESRD could open new avenues for therapeutic interventions and personalized treatment approaches in patients with this condition.
Topics: Humans; Metagenome; Gastrointestinal Microbiome; Kidney Failure, Chronic; Microbiota; Renal Insufficiency, Chronic; Feces; Clostridiales
PubMed: 37828586
DOI: 10.1186/s13059-023-03056-y -
Frontiers in Veterinary Science 2023
PubMed: 37822953
DOI: 10.3389/fvets.2023.1285992 -
AMB Express Oct 2023Postherpetic neuralgia (PHN) is a prevalent, intricate, and intractable form of neuropathic pain. The available evidence indicates that alterations in the gut microbiota...
Postherpetic neuralgia (PHN) is a prevalent, intricate, and intractable form of neuropathic pain. The available evidence indicates that alterations in the gut microbiota are significant environmental determinants in the development of chronic neuropathic pain. Nevertheless, the correlation between the gut microbiota and PHN remains elusive. A cross-sectional study was performed on a cohort of 27 patients diagnosed with PHN and 27 matched healthy controls. Fecal samples were collected and subjected to microbiota analysis using 16S ribosomal RNA gene sequencing. Comparable levels of bacterial richness and diversity were observed in the gut microbiota of PHN patients and healthy controls. A significant difference was observed in 37 genera between the two groups. Furthermore, the LEfSe method revealed that the abundance levels of Escherichia-Shigella, Streptococcus, Ligilactobacillus, and Clostridia_UCG-014_unclassified were elevated in PHN patients, while Eubacterium_hallii_group, Butyricicoccus, Tyzzerella, Dorea, Parasutterella, Romboutsia, Megamonas, and Agathobacter genera were reduced in comparison to healthy controls. Significantly, the discriminant model utilizing the predominant microbiota exhibited efficacy in distinguishing PHN patients from healthy controls, with an area under the curve value of 0.824. Moreover, Spearman correlation analysis demonstrated noteworthy correlations between various gut microbiota and clinical symptoms, including disease course, anxiety state, sleep quality, heat pain, pain intensity, and itching intensity. Gut microbiota dysbiosis exists in PHN patients, microbiome differences could be used to distinguish PHN patients from normal healthy individuals with high sensitivity and specificity, and altered gut microbiota are related to clinical manifestations, suggesting potentially novel prevention and therapeutic directions of PHN.
PubMed: 37803181
DOI: 10.1186/s13568-023-01614-y -
Journal of Microbiology and... Dec 2023Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human...
Biochemical gut metabolism of dietary bioactive compounds is of great significance in elucidating health-related issues at the molecular level. In this study, a human gut bacterium cleaving C-C glycosidic bond was screened from puerarin conversion to daidzein, and a new, gram-positive -glycoside-deglycosylating strain, sp. MRG-IFC3, was isolated from human fecal sample under anaerobic conditions. Though MRG-IFC3 biotransformed isoflavone -glycoside, it could not metabolize other -glycosides, such as vitexin, bergenin, and aloin. As evident from the production of the corresponding aglycons from various 7--glucosides, MRG-IFC3 strain also showed 7--glycoside cleavage activity; however, flavone 3--glucoside icariside II was not metabolized. In addition, for mechanism study, -glycosyl bond cleavage of puerarin by MRG-IFC3 strain was performed in DO GAM medium. The complete deuterium enrichment on C-8 position of daidzein was confirmed by H NMR spectroscopy, and the result clearly proved for the first time that daidzein is produced from puerarin. Two possible reaction intermediates, the quinoids and 8-dehydrodaidzein anion, were proposed for the production of daidzein-8d. These results will provide the basis for the mechanism study of stable -glycosidic bond cleavage at the molecular level.
Topics: Humans; Bacteria; Glycosides; Isoflavones; Glucosides; Feces
PubMed: 37789701
DOI: 10.4014/jmb.2308.08021