-
MBio 2012Gastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous...
Application of novel PCR-based methods for detection, quantitation, and phylogenetic characterization of Sutterella species in intestinal biopsy samples from children with autism and gastrointestinal disturbances.
UNLABELLED
Gastrointestinal disturbances are commonly reported in children with autism and may be associated with compositional changes in intestinal bacteria. In a previous report, we surveyed intestinal microbiota in ileal and cecal biopsy samples from children with autism and gastrointestinal dysfunction (AUT-GI) and children with only gastrointestinal dysfunction (Control-GI). Our results demonstrated the presence of members of the family Alcaligenaceae in some AUT-GI children, while no Control-GI children had Alcaligenaceae sequences. Here we demonstrate that increased levels of Alcaligenaceae in intestinal biopsy samples from AUT-GI children result from the presence of high levels of members of the genus Sutterella. We also report the first Sutterella-specific PCR assays for detecting, quantitating, and genotyping Sutterella species in biological and environmental samples. Sutterella 16S rRNA gene sequences were found in 12 of 23 AUT-GI children but in none of 9 Control-GI children. Phylogenetic analysis revealed a predominance of either Sutterella wadsworthensis or Sutterella stercoricanis in 11 of the individual Sutterella-positive AUT-GI patients; in one AUT-GI patient, Sutterella sequences were obtained that could not be given a species-level classification based on the 16S rRNA gene sequences of known Sutterella isolates. Western immunoblots revealed plasma IgG or IgM antibody reactivity to Sutterella wadsworthensis antigens in 11 AUT-GI patients, 8 of whom were also PCR positive, indicating the presence of an immune response to Sutterella in some children.
IMPORTANCE
Autism spectrum disorders affect ~1% of the population. Many children with autism have gastrointestinal (GI) disturbances that can complicate clinical management and contribute to behavioral problems. Understanding the molecular and microbial underpinnings of these GI issues is of paramount importance for elucidating pathogenesis, rendering diagnosis, and administering informed treatment. Here we describe an association between high levels of intestinal, mucoepithelial-associated Sutterella species and GI disturbances in children with autism. These findings elevate this little-recognized bacterium to the forefront by demonstrating that Sutterella is a major component of the microbiota in over half of children with autism and gastrointestinal dysfunction (AUT-GI) and is absent in children with only gastrointestinal dysfunction (Control-GI) evaluated in this study. Furthermore, these findings bring into question the role Sutterella plays in the human microbiota in health and disease. With the Sutterella-specific molecular assays described here, some of these questions can begin to be addressed.
Topics: Antibodies, Bacterial; Autistic Disorder; Bacterial Load; Bacteriological Techniques; Betaproteobacteria; Biopsy; Blotting, Western; Child; Child, Preschool; Cluster Analysis; DNA, Bacterial; DNA, Ribosomal; Female; Gastrointestinal Diseases; Humans; Immunoglobulin G; Immunoglobulin M; Intestinal Mucosa; Male; Phylogeny; Polymerase Chain Reaction; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 22233678
DOI: 10.1128/mBio.00261-11 -
BMC Neurology Jul 2023To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian...
OBJECTIVE
To investigate the potential causal link between genetic variants associated with gut microbiome and risk of intracranial aneurysm (IA) using two-sample mendelian randomization (MR).
METHODS
We performed two sets of MR analyses. At first, we selected the genome-wide statistical significant(P < 5 × 10) single nucleotide polymorphisms (SNPs) as instrumental variables (IVs). Then, we selected the locus-wide significant (P < 1 × 10) SNPs as IVs for the other set of analyses to obtain more comprehensive conclusions. Gut microbiome genetic association estimates were derived from a genome-wide association study (GWAS) of 18,473 individuals. Summary-level statistics for IA were obtained from 79,429 individuals, which included 7,495 cases and 71,934 controls.
RESULTS
On the basis of locus-wide significance level, inverse variance weighted(IVW) showed that Clostridia [(odds ratio (OR): 2.60; 95% confidence interval (CI): 1.00-6.72, P = 0.049)], Adlercreutzia (OR: 1.81; 95% CI: 1.10-2.99, P = 0.021) and Victivallis (OR: 1.38; 95% CI: 1.01-1.88, P = 0.044) were positively related with the risk of unruptured intracranial aneurysm(UIA); Weighted median results of MR showed Oscillospira (OR: 0.37; 95% CI: 0.17-0.84, P = 0.018) was negatively with the risk of UIA and Sutterella (OR: 1.84; 95% CI: 1.04-3.23, P = 0.035) was positively related with the risk of UIA; MR-Egger method analysis indicated that Paraprevotella (OR: 0.32; 95% CI: 0.13-0.80, P = 0.035) was negatively with the risk of UIA and Rhodospirillaceae (OR: 13.39; 95% CI: 1.44-124.47, P = 0.048) was positively related with the risk of UIA. The results suggest that Streptococcus (OR: 5.19; 95% CI: 1.25-21.56; P = 0.024) and Peptostreptococcaceae (OR: 4.92; 95% CI: 1.32-18.32; P = 0.018) may increase the risk of UIA according to genome-wide statistical significance thresholds.
CONCLUSION
This MR analysis indicates that there exists a beneficial or detrimental causal effect of gut microbiota composition on IAs.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Intracranial Aneurysm; Mendelian Randomization Analysis; Odds Ratio; Polymorphism, Single Nucleotide
PubMed: 37454067
DOI: 10.1186/s12883-023-03288-2 -
International Journal of Medical... Apr 2021As many inflammatory and metabolic disorders have been associated with structural deficits of the human gut microbiota, the principles and mechanisms that govern its... (Meta-Analysis)
Meta-Analysis
As many inflammatory and metabolic disorders have been associated with structural deficits of the human gut microbiota, the principles and mechanisms that govern its initialization and development are of considerable scientific interest and clinical relevance. However, our current understanding of the developing gut microbiota dynamics remains incomplete. We carried out a large-scale, comprehensive meta-analysis of over 1900 available metagenomic shotgun samples from neonates, infants, adolescents, and their families, using our recently introduced SameStr program for strain-level microbiota profiling and the detection of microbial strain transfer and persistence. We found robust associations between fecal microbiota composition and age, as well as delivery mode, which was measurable for up to two years of life. C-section was associated with increased relative abundances of non-gut species and delayed transition from a predominantly oxygen-tolerant to intolerant microbial community. Unsupervised networks based on shared strain profiles generated family-specific clusters connecting infants, their siblings, parents and grandparents and, in one case, suggested strain transfer between neonates from the same hospital ward, but could also be used to identify potentially mislabeled metagenome samples. Vaginally delivered newborns shared more strains with their mothers than C-section infants, but strain sharing was reduced if mothers underwent antibiotic treatment. Shared strains persisted in infants throughout the first year of life and belonged to the same bacterial species as strains that were shared between adults and their parents. Irrespective of delivery type, older children shared strains with their mothers and fathers and, into adulthood, could be accurately distinguished from unrelated sample pairs. Prominent fecal commensal bacteria were both among frequently transferred (e.g. Bacteroides and Sutterella) and newly acquired taxa (e.g. Blautia, Faecalibacterium, and Ruminococcus). Our meta-analysis presents a more detailed and comprehensive picture of the highly dynamic neonatal and infant fecal microbiota development than previous studies and presents evidence for taxonomic and functional compositional differences early in life between infants born naturally or by C-section, which persist well into adolescence.
Topics: Adolescent; Adult; Cesarean Section; Child; Feces; Female; Gastrointestinal Microbiome; Humans; Infant; Infant, Newborn; Metagenome; Microbiota; Pregnancy
PubMed: 33689953
DOI: 10.1016/j.ijmm.2021.151483 -
FEBS Open Bio Aug 2023Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. Metabolites and their sensors play an important role in the communication...
Ulcerative colitis (UC) is a recurrent inflammatory disease related to gut microbiota disorder. Metabolites and their sensors play an important role in the communication between gut microbes and their host. Our previous study revealed that G protein-coupled receptor 35 (GPR35) is a key guardian of kynurenic acid (KA) and a core element of the defense responses against gut damage. However, the mechanism remains unknown. In this study, a DSS-induced rat colitis model was established and 16S rRNA sequencing was applied to explore the influence of GPR35-mediated KA sensing on gut microbiota homeostasis. Our results demonstrated that GPR35-mediated KA sensing is a necessary component in maintaining gut barrier integrity against DSS-induced damage. Furthermore, we provide compelling evidence suggesting that GPR35-mediated KA sensing plays a crucial role in maintaining gut microbiota homeostasis, which contributes to alleviation of DSS-induced colitis. In addition, five classes (Actinobacteria, Beta-/Gamma-proteobacteria, Erysipelotrichi, and Coriobacteriia) and six genera (Corynebacterium, Allobaculum, Parabacteroides, Sutterella, Shigella, and Xenorhabdus) were identified as the marked bacterial taxa that characterized the progression and outcome of colitis and are regulated by GPR35-mediated KA sensing. Our findings highlight that GPR35-mediated KA sensing is an essential defense mechanism against disorder of gut microbiota in UC. The results provide insights into the key role of specific metabolites and their monitor in maintaining gut homeostasis.
Topics: Rats; Animals; Colitis, Ulcerative; Gastrointestinal Microbiome; Kynurenic Acid; RNA, Ribosomal, 16S; Colitis; Receptors, G-Protein-Coupled; Bacteria
PubMed: 37423235
DOI: 10.1002/2211-5463.13673 -
Frontiers in Nutrition 2022This study was aimed to evaluate the effects of low-carbohydrate diet (LC) and incorporated high-intensity interval training (HIIT) or moderate-intensity continuous...
OBJECTIVE
This study was aimed to evaluate the effects of low-carbohydrate diet (LC) and incorporated high-intensity interval training (HIIT) or moderate-intensity continuous training (MICT) on gut microbiota, and the associations between changes in gut microbiota and cardiometabolic health-related profiles.
METHODS
Fifty overweight/obese Chinese females (age 22.2 ± 3.3 years, body mass index 25.1 ± 3.1 kg/m) were randomized to the groups of LC, LC and HIIT (LC-HIIT, 10 repetitions of 6-s sprints and 9-s rest), and LC and MICT group (LC-MICT, cycling at 50-60% V̇O for 30 min). The LC-HIIT and LC-MICT experienced 20 training sessions over 4 weeks.
RESULTS
The 4-week LC intervention with/without additional training failed to change the Shannon, Chao 1, and Simpson indexes ( > 0.05), LC increased genus, and LC-HIIT reduced genus after intervention ( < 0.05). Groups with extra exercise training increased short-chain fatty acid-producing genus ( < 0.05) and reduced type 2 diabetes-related genus ( < 0.05) compared to LC. ( = -0.335) and ( = 0.334) were associated with changes in body composition ( < 0.05). Changes in , , and genera were positively associated with blood pressure (BP) changes ( = 0.392-0.445, < 0.05), whereas the changes in , , and genera were negatively associated with BP changes ( = -0.567 to -0.362, < 0.05).
CONCLUSION
LC intervention did not change the α-diversity and overall structure of gut microbiota. Combining LC with exercise training may have additional benefits on gut physiology. Specific microbial genera were associated with LC- and exercise-induced regulation of cardiometabolic health.
PubMed: 35592627
DOI: 10.3389/fnut.2022.884550 -
Life (Basel, Switzerland) Aug 2021Emerging evidences link gut microbiota to colorectal cancer (CRC) initiation and development. However, the CRC stage- and spatial-specific bacterial taxa were less...
Emerging evidences link gut microbiota to colorectal cancer (CRC) initiation and development. However, the CRC stage- and spatial-specific bacterial taxa were less investigated, especially in a Chinese cohort, leading to our incomplete understanding of the functional roles of gut microbiota in promoting CRC progression and recurrence. Here, we report the composition and structure of gut microbiota across CRC stages I, II and III, by analyzing the gut mucosal microbiomes of 75 triplet-paired samples collected from on-tumor, adjacent-tumor and off-tumor sites and 26 healthy controls. We observed tumor-specific pattern of mucosal microbiome profiles as CRC progressed and identified ten bacterial taxa with high abundances (>1%) as potential biomarkers for tumor initiation and development. and can serve as biomarkers for CRC stage I. , , , , , and can serve as biomarkers for CRC stage II, while , , , , and can serve as biomarkers for CRC stage III. These biomarkers classified CRC stages I, II and III distinguished from each other with an area under the receiver-operating curve (AUC) > 0.5. Moreover, co-occurrence and co-excluding network analysis of these genera showed strong correlations in CRC stage I, which were subsequently reduced in CRC stages II and III. Our findings provide a reference index for stage-specific CRC diagnosis and suggest stage-specific roles of , , and in driving CRC progression.
PubMed: 34440574
DOI: 10.3390/life11080831 -
BMC Genomics May 2021Long-read sequencing in metagenomics facilitates the assembly of complete genomes out of complex microbial communities. These genomes include essential biologic...
BACKGROUND
Long-read sequencing in metagenomics facilitates the assembly of complete genomes out of complex microbial communities. These genomes include essential biologic information such as the ribosomal genes or the mobile genetic elements, which are usually missed with short-reads. We applied long-read metagenomics with Nanopore sequencing to retrieve high-quality metagenome-assembled genomes (HQ MAGs) from a dog fecal sample.
RESULTS
We used nanopore long-read metagenomics and frameshift aware correction on a canine fecal sample and retrieved eight single-contig HQ MAGs, which were > 90% complete with < 5% contamination, and contained most ribosomal genes and tRNAs. At the technical level, we demonstrated that a high-molecular-weight DNA extraction improved the metagenomics assembly contiguity, the recovery of the rRNA operons, and the retrieval of longer and circular contigs that are potential HQ MAGs. These HQ MAGs corresponded to Succinivibrio, Sutterella, Prevotellamassilia, Phascolarctobacterium, Catenibacterium, Blautia, and Enterococcus genera. Linking our results to previous gastrointestinal microbiome reports (metagenome or 16S rRNA-based), we found that some bacterial species on the gastrointestinal tract seem to be more canid-specific -Succinivibrio, Prevotellamassilia, Phascolarctobacterium, Blautia_A sp900541345-, whereas others are more broadly distributed among animal and human microbiomes -Sutterella, Catenibacterium, Enterococcus, and Blautia sp003287895. Sutterella HQ MAG is potentially the first reported genome assembly for Sutterella stercoricanis, as assigned by 16S rRNA gene similarity. Moreover, we show that long reads are essential to detect mobilome functions, usually missed in short-read MAGs.
CONCLUSIONS
We recovered eight single-contig HQ MAGs from canine feces of a healthy dog with nanopore long-reads. We also retrieved relevant biological insights from these specific bacterial species previously missed in public databases, such as complete ribosomal operons and mobilome functions. The high-molecular-weight DNA extraction improved the assembly's contiguity, whereas the high-accuracy basecalling, the raw read error correction, the assembly polishing, and the frameshift correction reduced the insertion and deletion errors. Both experimental and analytical steps ensured the retrieval of complete bacterial genomes.
Topics: Animals; Burkholderiales; Dogs; Feces; Genome, Bacterial; Metagenome; Metagenomics; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 33957869
DOI: 10.1186/s12864-021-07607-0 -
Frontiers in Neuroscience 2022To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
OBJECTIVE
To characterize the intestinal flora of patients with epilepsy and its correlation with epilepsy.
METHODS
Patients with ages > 18 years were consecutively enrolled from the outpatient department, Affiliated Hospital of Guizhou Medical University from January 2018 to December 2019. A total of 71 subjects were recruited, including epilepsy patients ( = 41) as an observation group and patient family members ( = 30) as a control group. Fresh stool specimens of all the subjects were collected. The 16S ribosomal RNA sequencing was analyzed to determine changes in intestinal flora composition and its correlation with epilepsy. Subgroup analysis was then conducted. All patients with epilepsy were divided into an urban group ( = 21) and a rural group ( = 20) according to the region, and bioinformatics analyses were repeated between subgroups.
RESULTS
LEfSe analysis showed that , , , and had relatively increased abundance in the epilepsy group at the genus level. Correlation analysis suggested that sp. ( = 0.584, < 0.01), ( = 0.560, < 0.01), ( = 0.541, < 0.01), and ( = 0.506, < 0.01) were significantly positively correlated with the occurrence of epilepsy ( ≥ 0.5, < 0.05). PICRUSt function prediction analysis showed that there were significant differences in 16 pathways between the groups at level 3. Comparing the rural group with the urban group, increased at the phylum level and , , , and increased at the species level in the rural group.
CONCLUSION
There were significant differences in the composition and functional pathways of gut flora between epilepsy patients and patient family members. The may become a potential biomarker for the diagnosis of epilepsy.
PubMed: 35250450
DOI: 10.3389/fnins.2022.803538 -
Neural Regeneration Research May 2023Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting...
Studies have shown that gut microbiota metabolites can enter the central nervous system via the blood-spinal cord barrier and cause neuroinflammation, thus constituting secondary injury after spinal cord injury. To investigate the correlation between gut microbiota and metabolites and the possible mechanism underlying the effects of gut microbiota on secondary injury after spinal cord injury, in this study, we established mouse models of T8-T10 traumatic spinal cord injury. We used 16S rRNA gene amplicon sequencing and metabolomics to reveal the changes in gut microbiota and metabolites in fecal samples from the mouse model. Results showed a severe gut microbiota disturbance after spinal cord injury, which included marked increases in pro-inflammatory bacteria, such as Shigella, Bacteroides, Rikenella, Staphylococcus, and Mucispirillum and decreases in anti-inflammatory bacteria, such as Lactobacillus, Allobaculum, and Sutterella. Meanwhile, we identified 27 metabolites that decreased and 320 metabolites that increased in the injured spinal cord. Combined with pathway enrichment analysis, five markedly differential amino acids (L-leucine, L-methionine, L-phenylalanine, L-isoleucine and L-valine) were screened out, which play a pivotal role in activating oxidative stress and inflammatory responses following spinal cord injury. Integrated correlation analysis indicated that the alteration of gut microbiota was related to the differences in amino acids, which suggests that disturbances in gut microbiota might participate in the secondary injury through the accumulation of partial metabolites that activate oxidative stress and inflammatory responses. Findings from this study provide a new theoretical basis for improving the secondary injury after spinal cord injury through fecal microbial transplantation.
PubMed: 36254996
DOI: 10.4103/1673-5374.355769 -
Frontiers in Microbiology 2023To investigate the characteristic changes in the gut microbiota of patients with type A aortic dissection (AAD) and provide a theoretical basis for future...
OBJECTIVE
To investigate the characteristic changes in the gut microbiota of patients with type A aortic dissection (AAD) and provide a theoretical basis for future microbiome-oriented interventional studies.
METHODS
High-throughput 16S rDNA sequencing was performed on the stool samples of patients with and without (healthy control subjects) AAD. Using alpha and beta diversity analysis, we compared the gut microbiota composition of 20 patients with AAD and 20 healthy controls matched for gender, age, BMI, and geographical region. The accuracy of AAD prediction by differential microbiome was calculated using the random forest machine learning model. Targeted measurement of the plasma concentration of short-chain fatty acids (SCFAs), which are the main metabolites of the gut microbiome, was performed using gas chromatography-mass spectrometry (GC-MS). Spearman's correlation analysis was conducted to determine the relationships of gut microbiome and SCFAs with the clinical characteristics of subjects.
RESULTS
The differences in gut microbiota alpha diversity between patients with AAD and the healthy controls were not statistically significant (Shannon index: = 0.19; Chao1: = 0.4); however, the microbiota composition (beta diversity) was significantly different between the two groups (Anosim, = 0.001). was enriched at the phylum level, and the SCFA-producing genera , , , and and inflammation-related genera and were enriched at the genus level in the AAD group compared with those in the control group. The random forest model could predict AAD from gut microbiota composition with an accuracy of 87.5% and the area-under-curve (AUC) of the receiver operating characteristic curve was 0.833. The SCFA content of patients with AAD was higher than that of the control group, with the difference being statistically significant ( < 0.05). The different microflora and SCFAs were positively correlated with inflammatory cytokines.
CONCLUSION
To the best of our knowledge, this is the first demonstration of the presence of significant differences in the gut microbiome of patients with AAD and healthy controls. The differential microbiome exhibited high predictive potential toward AAD and was positively correlated with inflammatory cytokines. Our results will assist in the development of preventive and therapeutic treatment methods for patients with AAD.
PubMed: 36910178
DOI: 10.3389/fmicb.2023.1092360