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International Journal of Molecular... Feb 2024CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a...
CoronaVac immunogenicity decreases with time, and we aimed to investigate whether gut microbiota associate with longer-term immunogenicity of CoronaVac. This was a prospective cohort study recruiting two-dose CoronaVac recipients from three centres in Hong Kong. We collected blood samples at baseline and day 180 after the first dose and used chemiluminescence immunoassay to test for neutralizing antibodies (NAbs) against the receptor-binding domain (RBD) of wild-type SARS-CoV-2 virus. We performed shotgun metagenomic sequencing performed on baseline stool samples. The primary outcome was the NAb seroconversion rate (seropositivity defined as NAb ≥ 15AU/mL) at day 180. Linear discriminant analysis [LDA] effect size analysis was used to identify putative bacterial species and metabolic pathways. A univariate logistic regression model was used to derive the odds ratio (OR) of seropositivity with bacterial species. Of 119 CoronaVac recipients (median age: 53.4 years [IQR: 47.8-61.3]; male: 39 [32.8%]), only 8 (6.7%) remained seropositive at 6 months after vaccination. (logLDA score = 4.39) and (logLDA score = 3.89) were significantly enriched in seropositive than seronegative participants. Seropositivity was associated with (OR: 5.73; 95% CI: 1.32-29.55; = 0.022) and with borderline significance (OR: 3.27; 95% CI: 0.73-14.72; = 0.110). Additionally, was positively correlated with most enriched metabolic pathways in seropositive vaccinees, including the superpathway of adenosine nucleotide de novo biosynthesis I (logLDA score = 2.88) and II (logLDA score = 2.91), as well as pathways related to vitamin B biosynthesis, all of which are known to promote immune functions. In conclusion, certain gut bacterial species ( and ) and metabolic pathways were associated with longer-term CoronaVac immunogenicity.
Topics: Humans; Male; Middle Aged; Gastrointestinal Microbiome; Prospective Studies; Adenosine; Antibodies, Neutralizing; Antibodies, Viral; COVID-19 Vaccines; Vaccines, Inactivated
PubMed: 38473829
DOI: 10.3390/ijms25052583 -
Brain, Behavior, and Immunity Oct 2023The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The correlation between human gut microbiota and psychiatric diseases has long been recognized. Based on the heritability of the microbiome, genome-wide association studies on human genome and gut microbiome (mbGWAS) have revealed important host-microbiome interactions. However, establishing causal relationships between specific gut microbiome features and psychological conditions remains challenging due to insufficient sample sizes of previous studies of mbGWAS.
METHODS
Cross-cohort meta-analysis (via METAL) and multi-trait analysis (via MTAG) were used to enhance the statistical power of mbGWAS for identifying genetic variants and genes. Using two large mbGWAS studies (7,738 and 5,959 participants respectively) and12 disease-specific studies from the Psychiatric Genomics Consortium (PGC), we performed bidirectional two-sample mendelian randomization (MR) analyses between microbial features and psychiatric diseases (up to 500,199 individuals). Additionally, we conducted downstream gene- and gene-set-based analyses to investigate the shared biology linking gut microbiota and psychiatric diseases.
RESULTS
METAL and MTAG conducted in mbGWAS could boost power for gene prioritization and MR analysis. Increases in the number of lead SNPs and mapped genes were witnessed in 13/15 species and 5/10 genera after using METAL, and MTAG analysis gained an increase in sample size equivalent to expanding the original samples from 7% to 63%. Following METAL use, we identified a positive association between Bacteroides faecis and ADHD (OR, 1.09; 95 %CI, 1.02-1.16; P = 0.008). Bacteroides eggerthii and Bacteroides thetaiotaomicron were observed to be positively associated with PTSD (OR, 1.11; 95 %CI, 1.03-1.20; P = 0.007; OR, 1.11; 95 %CI, 1.01-1.23; P = 0.03). These findings remained stable across statistical models and sensitivity analyses. No genetic liabilities to psychiatric diseases may alter the abundance of gut microorganisms.Using biological annotation, we identified that those genes contributing to microbiomes (e.g., GRIN2A and RBFOX1) are expressed and enriched in human brain tissues.
CONCLUSIONS
Our statistical genetics strategy helps to enhance the power of mbGWAS, and our genetic findings offer new insights into biological pleiotropy and causal relationship between microbiota and psychiatric diseases.
Topics: Humans; Gastrointestinal Microbiome; Genome-Wide Association Study; Mendelian Randomization Analysis; Microbiota; Mental Disorders
PubMed: 37557965
DOI: 10.1016/j.bbi.2023.08.003 -
IDCases 2023is an obligately anaerobic, catalase-positive, motile, non-sporulating, gram-positive coccobacillus. Human infections are rare and have not been previously reported in...
BACKGROUND
is an obligately anaerobic, catalase-positive, motile, non-sporulating, gram-positive coccobacillus. Human infections are rare and have not been previously reported in Japan. Herein, we report the first case of perforated peritonitis with bacteremia in Japan.
CASE PRESENTATION
A 61-year-old Japanese man with advanced colorectal adenocarcinoma presented with fever and abdominal pain. Abdominal computed tomography revealed a low-density area with thinning of the sigmoid colon wall and air outside the intestinal tract, which was diagnosed as perforated peritonitis. Cultures of the ascitic fluid isolated , , , , and . Gram-positive rods were detected in the blood culture on admission after 4 days. The isolate was identified as via 16S ribosomal RNA (16S rRNA) sequencing. The patient underwent open abdominal washout and drainage via a transverse colon bifurcation colostomy. Intravenous meropenem (3 g/day) was administered for 5 days, followed by intravenous piperacillin-tazobactam (9 g/day) for 6 days, and then levofloxacin (500 mg/day) and metronidazole (1500 mg/day) intravenously for 15 days. Postoperatively, the patient gradually recovered. He was transferred to another palliative care hospital on day 38 after admission for worsening advanced colorectal cancer condition.
CONCLUSION
Bacteremia caused by is rare. 16S rRNA sequencing should be considered for the identification of gram-positive anaerobic rods that are difficult to diagnose by conventional methods.
PubMed: 37214185
DOI: 10.1016/j.idcr.2023.e01797 -
BMC Microbiology Mar 2023Plant-based diets offer more beneficial microbes and can modulate gut microbiomes to improve human health. We evaluated the effects of the plant-based OsomeFood Clean...
BACKGROUND
Plant-based diets offer more beneficial microbes and can modulate gut microbiomes to improve human health. We evaluated the effects of the plant-based OsomeFood Clean Label meal range ('AWE' diet), on the human gut microbiome.
METHODS
Over 21 days, ten healthy participants consumed OsomeFood meals for five consecutive weekday lunches and dinners and resumed their regular diets for other days/meals. On follow-up days, participants completed questionnaires to record satiety, energy and health, and provided stool samples. To document microbiome variations and identify associations, species and functional pathway annotations were analyzed by shotgun sequencing. Shannon diversity and regular diet calorie intake subsets were also assessed.
RESULTS
Overweight participants gained more species and functional pathway diversity than normal BMI participants. Nineteen disease-associated species were suppressed in moderate-responders without gaining diversity, and in strong-responders with diversity gains along with health-associated species. All participants reported improved short-chain fatty acids production, insulin and γ-aminobutyric acid signaling. Moreover, fullness correlated positively with Bacteroides eggerthii; energetic status with B. uniformis, B. longum, Phascolarctobacterium succinatutens, and Eubacterium eligens; healthy status with Faecalibacterium prausnitzii, Prevotella CAG 5226, Roseburia hominis, and Roseburia sp. CAG 182; and overall response with E. eligens and Corprococcus eutactus. Fiber consumption was negatively associated with pathogenic species.
CONCLUSION
Although the AWE diet was consumed for only five days a week, all participants, especially overweight ones, experienced improved fullness, health status, energy and overall responses. The AWE diet benefits all individuals, especially those of higher BMI or low-fiber consumption.
Topics: Humans; Gastrointestinal Microbiome; Overweight; Feces; Diet; Meals
PubMed: 36997838
DOI: 10.1186/s12866-023-02822-z -
Frontiers in Nutrition 2022To study the prevention and mechanism of oat antimicrobial peptides (AMPs) on enteritis. Oat protein was hydrolyzed by alkaline protease and isolated to obtain oat...
To study the prevention and mechanism of oat antimicrobial peptides (AMPs) on enteritis. Oat protein was hydrolyzed by alkaline protease and isolated to obtain oat antimicrobial peptides. Rat enteritis models were constructed using dextran sodium sulfate (DSS), and a blank group, a negative control group, a positive control group, and an experimental group (low dose, medium dose, and high dose) were established. Through pathological test, antioxidant test, intestinal microbial and metabolite determination, it was found that AMPS can improve the antioxidant capacity of colon, reduce the production of inflammatory cells, and have the effect of preventing enteritis. In addition, the AMPS group is able to change and reduce the abundance of and , increase the abundance of probiotics such as and and the diversity of intestinal microorganisms. Then, the combined analysis of microorganism and metabolites showed that and reduced the contents of amino acid and glucose and promoted the production of phospholipid, while promoted the synthesis of amino acid in the body. From the above, it can be seen that DSS causes damage to the mechanical barrier of the gut. Oat antimicrobial peptides provide a microbial barrier for the gut microbes, which produce acetic acid and succinic acid with small amounts of isobutyric acid, isovaleric acid, and lactic acid. The acidic metabolites produced reduce the pH of the gut and produce substances with antibacterial effects (such as lipophilic molecules, antibiotics, and hydroperoxides). Inhibit the growth and reproduction of other harmful bacteria, , from adhering to and colonizing the intestinal mucosa. Secreted short-chain fatty acids, such as acetate and butyric acid, maintain tight connections between the epithelial cells of the intestinal mucosa, thus protecting the mechanical barrier of the intestinal mucosa. Moreover, amino acids are converted into phospholipid metabolism through protein digestion and absorption to promote the production of phospholipid in the intestine and repair damaged cell membranes.
PubMed: 36712538
DOI: 10.3389/fnut.2022.1095483 -
European Journal of Clinical... Mar 2023Accumulating evidence has related the gut microbiota to colorectal cancer (CRC). Fusobacterium nucleatum has repeatedly been linked to colorectal tumorigenesis. The aim...
Accumulating evidence has related the gut microbiota to colorectal cancer (CRC). Fusobacterium nucleatum has repeatedly been linked to colorectal tumorigenesis. The aim of this study was to investigate microbial composition in different sampling sites, in order to profile the microbial dynamics with CRC progression. Further, we characterized the tumor-associated F. nucleatum subspecies. Here, we conducted Illumina Miseq next-generation sequencing of the 16S rRNA V4 region in biopsy samples, to investigate microbiota alterations in cancer patients, patients with adenomatous polyp, and healthy controls in Norway. Further, Fusobacterium positive tumor biopsies were subjected to MinION nanopore sequencing of Fusobacterium-specific amplicons to characterize the Fusobacterium species and subspecies. We found enrichment of oral biofilm-associated bacteria, Fusobacterium, Gemella, Parvimonas, Granulicatella, Leptotrichia, Peptostreptococcus, Campylobacter, Selenomonas, Porphyromonas, and Prevotella in cancer patients compared to adenomatous polyp patients and control patients. Higher abundance of amplicon sequence variants (ASVs) classified as Phascolarctobacterium, Bacteroides vulgatus, Bacteroides plebeius, Bacteroides eggerthii, Tyzzerella, Desulfovibrio, Frisingicoccus, Eubacterium coprostanoligenes group, and Lachnospiraceae were identified in cancer and adenomatous polyp patients compared to healthy controls. F. nucleatum ssp. animalis was the dominating subspecies. F. nucleatum ssp. nucleatum, F. nucleatum ssp. vincentii, Fusobacterium pseudoperiodonticum, Fusobacterium necrophorum, and Fusobacterium gonidiaformans were identified in five samples. Several biofilm-associated bacteria were enriched at multiple sites in cancer patients. Another group of bacteria was enriched in both cancer and polyps, suggesting that they may have a role in polyp development and possibly early stages of CRC.
Topics: Humans; RNA, Ribosomal, 16S; Fusobacterium nucleatum; Bacteria; Carcinogenesis; Gastrointestinal Microbiome; Adenomatous Polyps; Colorectal Neoplasms
PubMed: 36703031
DOI: 10.1007/s10096-023-04551-7 -
BMC Genomics Dec 2022The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations...
BACKGROUND
The gut microbiome has proven to be an important factor affecting obesity; however, it remains a challenge to identify consistent biomarkers across geographic locations and perform precisely targeted modulation for obese individuals.
RESULTS
This study proposed a systematic machine learning framework and applied it to 870 human stool metagenomes across five countries to obtain comprehensive regional shared biomarkers and conduct a personalized modulation analysis. In our pipeline, a heterogeneous ensemble feature selection diagram is first developed to determine an optimal subset of biomarkers through the aggregation of multiple techniques. Subsequently, a deep reinforcement learning method was established to alter the targeted composition to the desired healthy target. In this manner, we can realize personalized modulation by counterfactual inference. Consequently, a total of 42 species were identified as regional shared biomarkers, and they showed good performance in distinguishing obese people from the healthy group (area under curve (AUC) =0.85) when demonstrated on validation datasets. In addition, by pooling all counterfactual explanations, we found that Akkermansia muciniphila, Faecalibacterium prausnitzii, Prevotella copri, Bacteroides dorei, Bacteroides eggerthii, Alistipes finegoldii, Alistipes shahii, Eubacterium sp. _CAG_180, and Roseburia hominis may be potential broad-spectrum targets with consistent modulation in the multi-regional obese population.
CONCLUSIONS
This article shows that based on our proposed machine-learning framework, we can obtain more comprehensive and accurate biomarkers and provide modulation analysis for the obese population. Moreover, our machine-learning framework will also be very useful for other researchers to further obtain biomarkers and perform counterfactual modulation analysis in different diseases.
Topics: Humans; Gastrointestinal Microbiome; Obesity; Feces; Biomarkers; Machine Learning
PubMed: 36564713
DOI: 10.1186/s12864-022-09087-2 -
Biomolecular NMR Assignments Oct 2022To fully utilize carbohydrates from seaweed biomass, the degradation of the family of polysaccharides known as alginates must be understood. A step in the degradation of...
To fully utilize carbohydrates from seaweed biomass, the degradation of the family of polysaccharides known as alginates must be understood. A step in the degradation of alginate is the conversion of 4,5-unsaturated monouronates to 4-deoxy-L-erythro-5-hexoseulose catalysed by the enzyme KdgF. In this study BeKdgF from Bacteroides eggerthii from the human gut microbiota has been produced isotopically labelled in Escherichia coli. Here the H, C, and N NMR chemical shift assignment for BeKdgF is reported.
Topics: Alginates; Bacteroides; Escherichia coli; Humans; Nuclear Magnetic Resonance, Biomolecular; Polysaccharides
PubMed: 36042150
DOI: 10.1007/s12104-022-10102-6 -
Novel Thermostable Heparinase Based on the Genome of Bacteroides Isolated from Human Gut Microbiota.Foods (Basel, Switzerland) May 2022Among the nutrients available to the human gut microbiota, the complex carbohydrates and glycosaminoglycans are important sources of carbon for some of the species of...
Among the nutrients available to the human gut microbiota, the complex carbohydrates and glycosaminoglycans are important sources of carbon for some of the species of human gut microbiota. Glycosaminoglycan (heparin) from the host is a highly preferred carbohydrate for . To explore how gut microbiota can effectively use heparin as a carbon source for growth, we conducted a screening of the Carbohydrate-Active enzymes (CAZymes) database for lytic enzymes of the PL13 family and Research Center of Food Biotechnology at School of Food Science and Technology of Jiangnan University database of to identify novel glycosaminoglycan-degrading bacterial strains. Four species (, , , and ) that degraded heparin were selected for further studies. Analysis of the polysaccharide utilization sites of the four strains revealed that all of them harbored enzyme encoding genes of the PL13 family. Functional analysis revealed the activity of CAZymes in a medium containing heparin as the sole carbon source, suggesting their potential to degrade heparin and support growth. The four enzymes were heterologous expressed, and their enzymatic properties, kinetics, and thermal stability were determined. The lytic enzyme of had high enzymatic activity and thermal stability. The features that cause this high thermal stability were elucidated based on an examination of the three-dimensional structure of the protein. Our findings provide an important theoretical basis for the application of glycosaminoglycans and glycosaminoglycan-degrading enzymes in the medical and biotechnology industries, and an important scientific basis for precision nutrition and medical intervention studies using gut microbiota or enzymes as targets.
PubMed: 35627031
DOI: 10.3390/foods11101462 -
MSystems Jun 2022Emerging evidence shows that modulation of the microbiome can suppress intra-abdominal hypertension (IAH)-induced intestinal barrier damage through the regulation of...
Multi-omic Profiling Reveals that Intra-abdominal-Hypertension-Induced Intestinal Damage Can Be Prevented by Microbiome and Metabolic Modulations with 5-Hydroxyindoleacetic Acid as a Diagnostic Marker.
Emerging evidence shows that modulation of the microbiome can suppress intra-abdominal hypertension (IAH)-induced intestinal barrier damage through the regulation of amino acid (AA) biosynthesis. Here, we investigated the protective effects of orally gavaged Lactobacillus acidophilus L-92 (L92) and a mixture of AA in rats with induced IAH. The results showed that both L92 and AA pretreatments effectively mitigated IAH-induced intestinal damage. Interestingly, L92 but not AA prevented metagenomic changes induced by IAH. Bacteroides fragilis, Bacteroides eggerthii, Bacteroides ovatus, Faecalibacterium prausnitzii, , and extensively altered functional pathways were associated with L92-mediated host protection. Metabolomic profiling revealed that tryptophan metabolism was involved in both L92- and AA-mediated gut protection. The tryptophan metabolite 5-hydroxyindoleacetic acid (5-HIAA) is a sensitive biomarker for IAH in rats and patients with either gut-derived sepsis ( = 41) or all-source sepsis ( = 293). In conclusion, we show that microbiome and metabolic modulations can effectively prevent IAH-induced intestinal damage and that 5-HIAA is a potential metabolic marker for IAH and sepsis. Gut protection through modulation of the microbiome for critically ill patients has been gaining much attention recently. Intra-abdominal hypertension (IAH) is a prevailing clinical feature of acute gastrointestinal injuries in critically ill patients, characterized by nonspecific intestinal barrier damage. Prolonged IAH can induce or aggravate the development of sepsis and multiorgan dysfunctions. Therefore, the prevention of IAH-induced damage in rats through microbiome and metabolic interventions by commercially available L92 and AA treatments and the identification of 5-HIAA as an important marker for IAH/sepsis have important clinical implications for the treatment and early diagnosis of critically ill patients.
Topics: Rats; Animals; Intra-Abdominal Hypertension; Hydroxyindoleacetic Acid; Critical Illness; Multiomics; Tryptophan; Microbiota; Sepsis; Hypertension
PubMed: 35574681
DOI: 10.1128/msystems.01204-21