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Cell Genomics May 2024The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we...
The gut microbiome displays genetic differences among populations, and characterization of the genomic landscape of the gut microbiome in China remains limited. Here, we present the Chinese Gut Microbial Reference (CGMR) set, comprising 101,060 high-quality metagenomic assembled genomes (MAGs) of 3,707 nonredundant species from 3,234 fecal samples across primarily rural Chinese locations, 1,376 live isolates mainly from lactic acid bacteria, and 987 novel species relative to worldwide databases. We observed region-specific coexisting MAGs and MAGs with probiotic and cardiometabolic functionalities. Preliminary mouse experiments suggest a probiotic effect of two Faecalibacillus intestinalis isolates in alleviating constipation, cardiometabolic influences of three Bacteroides fragilis_A isolates in obesity, and isolates from the genera Parabacteroides and Lactobacillus in host lipid metabolism. Our study expands the current microbial genomes with paired isolates and demonstrates potential host effects, contributing to the mechanistic understanding of host-microbe interactions.
PubMed: 38740021
DOI: 10.1016/j.xgen.2024.100559 -
Gut Microbes 2024Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the functional implications...
Extensive research has explored the role of gut microbiota in colorectal cancer (CRC). Nonetheless, metatranscriptomic studies investigating the functional implications of host-microbe interactions in CRC are scarce. Therefore, we characterized the influence of CRC core pathogens and biofilms on the tumor microenvironment (TME) in 40 CRC, paired normal, and healthy tissue biopsies using fluorescence hybridization (FISH) and dual-RNA sequencing. FISH revealed that . was associated with increased bacterial biomass and inflammatory response in CRC samples. Dual-RNA sequencing demonstrated increased expression of pro-inflammatory cytokines, defensins, matrix-metalloproteases, and immunomodulatory factors in CRC samples with high bacterial activity. In addition, bacterial activity correlated with the infiltration of several immune cell subtypes, including M2 macrophages and regulatory T-cells in CRC samples. Specifically, and correlated with the infiltration of neutrophils and CD4 T-cells, respectively. The collective bacterial activity/biomass appeared to exert a more significant influence on the TME than core pathogens, underscoring the intricate interplay between gut microbiota and CRC. These results emphasize how biofilms and core pathogens shape the immune phenotype and TME in CRC while highlighting the need to extend the bacterial scope beyond CRC pathogens to advance our understanding and identify treatment targets.
Topics: Colorectal Neoplasms; Humans; Biofilms; Tumor Microenvironment; Gastrointestinal Microbiome; Male; Female; Bacteria; Middle Aged; In Situ Hybridization, Fluorescence; Aged; Fusobacterium nucleatum; Cytokines; Macrophages; Phenotype; Bacteroides fragilis
PubMed: 38726597
DOI: 10.1080/19490976.2024.2350156 -
Nature Communications May 2024The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and...
The gut microbiota and microglia play critical roles in Alzheimer's disease (AD), and elevated Bacteroides is correlated with cerebrospinal fluid amyloid-β (Aβ) and tau levels in AD. We hypothesize that Bacteroides contributes to AD by modulating microglia. Here we show that administering Bacteroides fragilis to APP/PS1-21 mice increases Aβ plaques in females, modulates cortical amyloid processing gene expression, and down regulates phagocytosis and protein degradation microglial gene expression. We further show that administering Bacteroides fragilis to aged wild-type male and female mice suppresses microglial uptake of Aβ1-42 injected into the hippocampus. Depleting murine Bacteroidota with metronidazole decreases amyloid load in aged 5xFAD mice, and activates microglial pathways related to phagocytosis, cytokine signaling, and lysosomal degradation. Taken together, our study demonstrates that members of the Bacteroidota phylum contribute to AD pathogenesis by suppressing microglia phagocytic function, which leads to impaired Aβ clearance and accumulation of amyloid plaques.
Topics: Animals; Microglia; Alzheimer Disease; Amyloid beta-Peptides; Plaque, Amyloid; Disease Models, Animal; Female; Phagocytosis; Mice; Male; Mice, Transgenic; Bacteroides fragilis; Gastrointestinal Microbiome; Humans; Mice, Inbred C57BL; Hippocampus
PubMed: 38719797
DOI: 10.1038/s41467-024-47683-w -
Anaerobe May 2024This paper reports a case of Bacteroides fragilis induced spondylitis. Diagnosis was confirmed through blood culture and metagenomic sequencing of pus for pathogen...
This paper reports a case of Bacteroides fragilis induced spondylitis. Diagnosis was confirmed through blood culture and metagenomic sequencing of pus for pathogen detection. Due to persistent lumbar pain, surgical intervention became imperative, resulting in favorable postoperative outcomes. A detailed patient history revealed a severe episode of oral ulceration two weeks before symptom onset, although a direct link to the infection remained elusive. Leveraging insights from this case, we conducted a comprehensive literature review on B. fragilis spondylitis, elucidating clinical manifestations, diagnostic methodologies, and therapeutic strategies.
PubMed: 38718918
DOI: 10.1016/j.anaerobe.2024.102863 -
Cellular and Molecular Gastroenterology... May 2024Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system,...
BACKGROUND & AIMS
Gut bacterial sphingolipids, primarily produced by Bacteroidetes, have dual roles as bacterial virulence factors and regulators of the host mucosal immune system, including regulatory T cells and iNKT cells. IBD patients display altered sphingolipids profiles in fecal samples. However, how bacterial sphingolipids modulate mucosal homeostasis and regulate intestinal inflammation remains unclear.
METHODS
We utilized DSS-induced colitis in mice mono-colonized with Bacteroides fragilis strains expressing or lacking sphingolipids to assess the influence of bacterial sphingolipids on intestinal inflammation employing transcriptional, protein, and cellular analyses. Colonic explant and organoid were used to study the function of bacterial sphingolipids. Host mucosal immune cells and cytokines were profiled and characterized using flow cytometry, ELISA, and Western Blot, and cytokine function in vivo was investigated by monoclonal antibody injection.
RESULTS
B. fragilis sphingolipids exacerbated intestinal inflammation. Mice mono-colonized with B. fragilis lacking sphingolipids exhibited less severe DSS-induced colitis. This amelioration of colitis was associated with increased production of interleukin-22 by ILC3. Mice colonized with B. fragilis lacking sphingolipids following DSS treatment showed enhanced epithelial STAT3 activity, intestinal cell proliferation, and antimicrobial peptide production. Protection against DSS colitis associated with B. fragilis lacking sphingolipids was reversed upon IL-22 blockade. Furthermore, bacterial sphingolipids restricted epithelial IL-18 production following DSS treatment and interfered with IL-22 production by a subset of ILC3 cells expressing both IL-18R and MHC II.
CONCLUSION
B. fragilis-derived sphingolipids exacerbate mucosal inflammation by impeding epithelial IL-18 expression and concomitantly suppressing the production of IL-22 by ILC3 cells.
PubMed: 38704148
DOI: 10.1016/j.jcmgh.2024.04.007 -
Cureus Apr 2024A 70-year-old female, diagnosed with mitochondrial diabetes mellitus (MDM) showing previously a point mutation at mitochondrial DNA 3316G>A, noticed urinary tract...
A 70-year-old female, diagnosed with mitochondrial diabetes mellitus (MDM) showing previously a point mutation at mitochondrial DNA 3316G>A, noticed urinary tract infection and diabetic gangrene of the foot with Gram-negative bacteremia, followed by aggressive jaundice with high serum level of direct bilirubin. She died two months after the symptom onset. At autopsy, multiple foci of bacteremia-induced hemorrhagic infarction were observed in the congestive bilateral lungs, whereas the cholestatic liver revealed no overt gross cholangiectasis. Microscopic findings characteristically showed many bile thrombi in the biliary canaliculi of hepatic lobules without any evidence of severe shock liver. Finally, we diagnosed it exclusively as sepsis-associated cholestasis due to the marked elevation of Gram-negative bacteria-derived endotoxins and inflammatory cytokines. We propose that these unique liver features in our MDM case might be one of the new clues to unveil its enigmatic etiology.
PubMed: 38694673
DOI: 10.7759/cureus.57418 -
Investigative Ophthalmology & Visual... May 2024To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may...
PURPOSE
To identify compositional differences in the gut microbiome of nonmyopes (NM) and myopes using 16S ribosomal RNA sequencing and to investigate whether the microbiome may contribute to the onset or progression of the condition.
METHODS
Faecal samples were collected from 52 adult participants, of whom 23 were NM, 8 were progressive myopes (PM), and 21 were stable myopes (SM). The composition of the gut microbiota in each group was analysed using 16S ribosomal RNA gene sequencing.
RESULTS
There were no significant differences in alpha and beta diversity between the three groups (NM, PM, and SM). However, the distributions of Bifidobacterium, Bacteroides, Megamonas, Faecalibacterium, Coprococcus, Dorea, Roseburia, and Blautia were significantly higher in the myopes (SM and PM combined) when compared with emmetropes. The myopes exhibited significantly greater abundance of bacteria that are linked to the regulation of dopaminergic signalling, such as Clostridium, Ruminococcus, Bifidobacterium, and Bacteroides. Individuals with stable myopia were found to have a significantly higher proportion of Prevotella copri than those with progressive myopia. Bifidobacterium adolescentis, a gamma-aminobutyric acid (GABA)-producing bacterium, was significantly higher in all myopes than in NM and, in the comparison between SM and PM, it is significantly higher in SM. B. uniformis and B. fragilis, both GABA-producing Bacteroides, were present in relatively high abundance in all myopes and in SM compared with PM, respectively.
CONCLUSIONS
The presence of bacteria related to dopamine effect and GABA-producing bacteria in the gut microbiome of myopes may suggest a role of these microorganisms in the onset and progression of myopia.
Topics: Humans; Male; Adult; Female; Gastrointestinal Microbiome; Feces; RNA, Ribosomal, 16S; Myopia; Bacteria; Young Adult; Middle Aged; DNA, Bacterial
PubMed: 38691091
DOI: 10.1167/iovs.65.5.2 -
Frontiers in Microbiology 2024It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and...
BACKGROUND
It has been suggested in several observational studies that migraines are associated with the gut microbiota. It remains unclear, however, how the gut microbiota and migraines are causally related.
METHODS
We performed a bidirectional two-sample mendelian randomization study. Genome-wide association study (GWAS) summary statistics for the gut microbiota were obtained from the MiBioGen consortium ( = 18,340) and the Dutch Microbiota Project ( = 7,738). Pooled GWAS data for plasma metabolites were obtained from four different human metabolomics studies. GWAS summary data for migraine (cases = 48,975; controls = 450,381) were sourced from the International Headache Genetics Consortium. We used inverse-variance weighting as the primary analysis. Multiple sensitivity analyses were performed to ensure the robustness of the estimated results. We also conducted reverse mendelian randomization when a causal relationship between exposure and migraine was found.
RESULTS
(OR = 1.12, 95% CI: 1.05-1.20) was a risk factor for migraine. (OR = 0.93, 95% CI: 0.88-0.99), ( group; OR = 0.94, 95% CI: 0.90-0.98), and (OR = 0.97, 95% CI: 0.94-1.00) may have a suggestive association with a lower migraine risk. Functional pathways of methionine synthesis (OR = 0.89, 95% CI: 0.83-0.95) associated with microbiota abundance and plasma hydrocinnamate (OR = 0.85, 95% CI: 0.73-1.00), which are downstream metabolites of and , respectively, may also be associated with lower migraine risk. No causal association between migraine and the gut microbiota or metabolites was found in reverse mendelian randomization analysis. Both significant horizontal pleiotropy and significant heterogeneity were not clearly identified.
CONCLUSION
This Mendelian randomization analysis showed that was associated with an increased risk of migraine, while some bacteria in the gut microbiota may reduce migraine risk. These findings provide a reference for a deeper comprehension of the role of the gut-brain axis in migraine as well as possible targets for treatment interventions.
PubMed: 38690367
DOI: 10.3389/fmicb.2024.1325047 -
Journal of Global Infectious Diseases 2024
PubMed: 38680751
DOI: 10.4103/jgid.jgid_184_23 -
Science (New York, N.Y.) Apr 2024A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater...
A role for vitamin D in immune modulation and in cancer has been suggested. In this work, we report that mice with increased availability of vitamin D display greater immune-dependent resistance to transplantable cancers and augmented responses to checkpoint blockade immunotherapies. Similarly, in humans, vitamin D-induced genes correlate with improved responses to immune checkpoint inhibitor treatment as well as with immunity to cancer and increased overall survival. In mice, resistance is attributable to the activity of vitamin D on intestinal epithelial cells, which alters microbiome composition in favor of , which positively regulates cancer immunity. Our findings indicate a previously unappreciated connection between vitamin D, microbial commensal communities, and immune responses to cancer. Collectively, they highlight vitamin D levels as a potential determinant of cancer immunity and immunotherapy success.
Topics: Animals; Female; Humans; Male; Mice; Bacteroides fragilis; Gastrointestinal Microbiome; Immune Checkpoint Inhibitors; Immunotherapy; Intestinal Mucosa; Mice, Inbred C57BL; Neoplasms; Vitamin D; Diet; Cell Line, Tumor; Calcifediol; Vitamin D-Binding Protein
PubMed: 38662827
DOI: 10.1126/science.adh7954