-
Science Advances Dec 2023Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We...
Emerging evidence implicates gut microbial metabolism in neurodevelopmental disorders, but its influence on typical neurodevelopment has not been explored in detail. We investigated the relationship between the microbiome and neuroanatomy and cognition of 381 healthy children, demonstrating that differences in microbial taxa and genes are associated with overall cognitive function and the size of brain regions. Using a combination of statistical and machine learning models, we showed that species including , , and were enriched or depleted in children with higher cognitive function scores. Microbial metabolism of short-chain fatty acids was also associated with cognitive function. In addition, machine models were able to predict the volume of brain regions from microbial profiles, and taxa that were important in predicting cognitive function were also important for predicting individual brain regions and specific subscales of cognitive function. These findings provide potential biomarkers of neurocognitive development and may enable development of targets for early detection and intervention.
Topics: Child; Humans; Neuroanatomy; Feces; Cognition; Brain; Gastrointestinal Microbiome
PubMed: 38134274
DOI: 10.1126/sciadv.adi0497 -
World Journal of Gastroenterology Oct 2023The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small...
BACKGROUND
The small intestine is known to play a crucial role in the development and remission of diabetes mellitus (DM). However, the exact mechanism by which mid-small intestinal bypass improves glucose metabolism in diabetic rats is not fully understood.
AIM
To elucidate the mechanisms by which mid-small intestinal bypass improves glucose metabolism.
METHODS
Streptozotocin (STZ) was used to induce DM in Sprague-Dawley (SD) rats at a dose of 60 mg/kg. The rats were then randomly divided into two groups: The mid-small intestine bypass (MSIB) group and the sham group (underwent switch laparotomy). Following a 6-wk recovery period post-surgery, the rats underwent various assessments, including metabolic parameter testing, analysis of liver glycogen levels, measurement of key gluconeogenic enzyme activity, characterization of the gut microbiota composition, evaluation of hormone levels, determination of bile acid concentrations, and assessment of the expression of the intestinal receptors Takeda G protein-coupled receptor 5 and farnesoid X receptor.
RESULTS
The MSIB group of rats demonstrated improved glucose metabolism and lipid metabolism, along with increased hepatic glycogen content. Furthermore, there was a decrease in the expression of the key gluconeogenic enzymes phosphoenolpyruvate carboxykinase 1 and glucose-6-phosphatase. Importantly, the MSIB group exhibited a substantial increase in the abundances of intestinal , , , and . Moreover, higher levels of secondary bile acids, such as intestinal lithocholic acid, were observed in this group. Remarkably, the changes in the gut microbiota showed a significant correlation with the expression of key gluconeogenic enzymes and glucagon-like peptide 1 (GLP-1) at 6 wk postoperatively, highlighting their potential role in glucose regulation. These findings highlight the beneficial effects of mid-small intestine bypass on glucose metabolism and the associated modulation of the gut microbiota.
CONCLUSION
The findings of this study demonstrate that the introduction of postoperative intestinal in the mid-small intestine contributes to the enhancement of glucose metabolism in nonobese diabetic rats. This improvement is attributed to the increased inhibition of hepatic gluconeogenesis mediated by GLP-1, resulting in a favorable modulation of glucose homeostasis.
Topics: Rats; Animals; Gluconeogenesis; Glucagon-Like Peptide 1; Clostridium symbiosum; Jejunoileal Bypass; Diabetes Mellitus, Experimental; Rats, Sprague-Dawley; Gastric Bypass; Glucose; Homeostasis; Blood Glucose
PubMed: 37900993
DOI: 10.3748/wjg.v29.i39.5471 -
BioRxiv : the Preprint Server For... Oct 2023In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand...
In metagenomics, the pool of uncharacterized microbial enzymes presents a challenge for functional annotation. Among these, carbohydrate-active enzymes (CAZymes) stand out due to their pivotal roles in various biological processes related to host health and nutrition. Here, we present CAZyLingua, the first tool that harnesses protein language model embeddings to build a deep learning framework that facilitates the annotation of CAZymes in metagenomic datasets. Our benchmarking results showed on average a higher F1 score (reflecting an average of precision and recall) on the annotated genomes of , and compared to the traditional sequence homology-based method in dbCAN2. We applied our tool to a paired mother/infant longitudinal dataset and revealed unannotated CAZymes linked to microbial development during infancy. When applied to metagenomic datasets derived from patients affected by fibrosis-prone diseases such as Crohn's disease and IgG4-related disease, CAZyLingua uncovered CAZymes associated with disease and healthy states. In each of these metagenomic catalogs, CAZyLingua discovered new annotations that were previously overlooked by traditional sequence homology tools. Overall, the deep learning model CAZyLingua can be applied in combination with existing tools to unravel intricate CAZyme evolutionary profiles and patterns, contributing to a more comprehensive understanding of microbial metabolic dynamics.
PubMed: 37961379
DOI: 10.1101/2023.10.23.563620 -
Microbiome Jan 2024The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and...
BACKGROUND
The increasing prevalence of neurocognitive disorders (NCDs) in the aging population worldwide has become a significant concern due to subjectivity of evaluations and the lack of precise diagnostic methods and specific indicators. Developing personalized diagnostic strategies for NCDs has therefore become a priority.
RESULTS
Multimodal electroencephalography (EEG) data of a matched cohort of normal aging (NA) and NCDs seniors were recorded, and their faecal samples and urine exosomes were collected to identify multi-omics signatures and metabolic pathways in NCDs by integrating metagenomics, proteomics, and metabolomics analysis. Additionally, experimental verification of multi-omics signatures was carried out in aged mice using faecal microbiota transplantation (FMT). We found that NCDs seniors had low EEG power spectral density and identified specific microbiota, including Ruminococcus gnavus, Enterocloster bolteae, Lachnoclostridium sp. YL 32, and metabolites, including L-tryptophan, L-glutamic acid, gamma-aminobutyric acid (GABA), and fatty acid esters of hydroxy fatty acids (FAHFAs), as well as disturbed biosynthesis of aromatic amino acids and TCA cycle dysfunction, validated in aged mice. Finally, we employed a support vector machine (SVM) algorithm to construct a machine learning model to classify NA and NCDs groups based on the fusion of EEG data and multi-omics profiles and the model demonstrated 92.69% accuracy in classifying NA and NCDs groups.
CONCLUSIONS
Our study highlights the potential of multi-omics profiling and EEG data fusion in personalized diagnosis of NCDs, with the potential to improve diagnostic precision and provide insights into the underlying mechanisms of NCDs. Video Abstract.
Topics: Humans; Animals; Mice; Aged; Multiomics; Proteomics; Metagenomics; Metabolomics; Electroencephalography
PubMed: 38243335
DOI: 10.1186/s40168-023-01717-5 -
Clinical and Experimental... 2024The diagnosis of irritable bowel syndrome (IBS) is based on symptom-based criteria due to lack of reliable disease-specific biomarkers. Gut microbiota is perturbed in... (Review)
Review
A Systematic Review: Fecal Bacterial Profile in Patients with Irritable Bowel Syndrome Analyzed with the GA-Map Dysbiosis Test Based on the 16S rRNA Gene of Bacterial Species or Groups.
PURPOSE
The diagnosis of irritable bowel syndrome (IBS) is based on symptom-based criteria due to lack of reliable disease-specific biomarkers. Gut microbiota is perturbed in IBS and when comparing different methods used to analyze gut microbiota, the results might be obscured. Therefore, in this systematic review we aimed to investigate the profile of fecal bacterial markers and dysbiosis index (DI) in patients with IBS and IBS subgroups compared to healthy controls (HCs) conducted by the same method (GA-map Dysbiosis Test based on16S rRNA sequencing).
MATERIAL AND METHOD
We searched PubMed, EMBASE (Ovid) and Cochrane Library for case-control studies comparing fecal gut microbiota analyzed with the GA-map Dysbiosis Test (Oslo, Norway) in patients with IBS and HCs. Our outcomes were the difference in fecal bacterial markers and DI in patients with IBS and IBS subgroups compared to HCs.
RESULTS
The search identified 28 citations; five articles were included. Most studies evaluated fecal bacterial markers and DI in patients with diarrhea-predominant IBS (IBS-D). Results of fecal bacteria profile in IBS and IBS subgroups compared to HCs are inconsistent, however, two studies showed increased levels of in IBS-D compared to HCs and results of DI indicated IBS and IBS subgroups (especially IBS-D) having higher DI compared to HCs.
CONCLUSION
This systematic review revealed inconsistent findings in respect to differences in bacterial markers between IBS and IBS subgroups with HCs in studies using the GA-map Dysbiosis Test based on 16S rRNA sequencing. However, the test is quite novel, and few studies have used the method so far. More research comparing fecal microbiota profile differences in IBS and IBS subgroups compared to HCs utilizing the same method of analysis is needed to give us further insight into the gut bacteria profile in IBS and the clinical consequences of intestinal dysbiosis.
PubMed: 38646157
DOI: 10.2147/CEG.S451675 -
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 -
Scientific Reports Feb 2024High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and...
High-fat diet-induced obesity is a pandemic caused by an inactive lifestyle and increased consumption of Western diets and is a major risk factor for diabetes and cardiovascular diseases. In contrast, exercise can positively influence gut microbial diversity and is linked to a decreased inflammatory state. To understand the gut microbial variations associated with exercise and high-fat diet over time, we conducted a longitudinal study to examine the effect of covariates on gut microbial diversity and composition. Young mice were divided into four groups: Chow-diet (CHD), high-fat diet (HFD), high-fat diet + exercise (HFX), and exercise only (EXE) and underwent experimental intervention for 12 weeks. Fecal samples at week 0 and 12 were collected for DNA extraction, followed by 16S library preparation and sequencing. Data were analyzed using QIIME 2, R and MicrobiomeAnalyst. The Bacteroidetes-to-Firmicutes ratio decreased fivefold in the HFD and HFX groups compared to that in the CHD and EXE groups and increased in the EXE group over time. Alpha diversity was significantly increased in the EXE group longitudinally (p < 0.02), whereas diversity (Shannon, Faith's PD, and Fisher) and richness (ACE) was significantly reduced in the HFD (p < 0.005) and HFX (p < 0.03) groups over time. Beta diversity, based on the Jaccard, Bray-Curtis, and unweighted UniFrac distance metrics, was significant among the groups. Prevotella, Paraprevotella, Candidatus arthromitus, Lactobacillus salivarius, L. reuteri, Roseburia, Bacteroides uniformis, Sutterella, and Corynebacterium were differentially abundant in the chow-diet groups (CHD and EXE). Exercise significantly reduced the proportion of taxa characteristic of a high-fat diet, including Butyricimonas, Ruminococcus gnavus, and Mucispirillum schaedleri. Diet, age, and exercise significantly contributed to explaining the bacterial community structure and diversity in the gut microbiota. Modulating the gut microbiota and maintaining its stability can lead to targeted microbiome therapies to manage chronic and recurrent diseases and infections.
Topics: Mice; Animals; Diet, High-Fat; Gastrointestinal Microbiome; Longitudinal Studies; Obesity; Bacteroidetes; Mice, Inbred C57BL
PubMed: 38332014
DOI: 10.1038/s41598-024-52852-4 -
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 -
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