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Heliyon May 2024The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role...
The glioblastoma brain tumour (GBM) stands out as the most aggressive and resistant-to-treatment malignancy. Nevertheless, the gut-brain connection plays a pivotal role in influencing the growth and activation of the central nervous system. In this particular investigation, we aimed to assess and characterize the gut microbial ecosystem in GBM patients, both quantitatively and qualitatively. We collected faecal samples from 15 healthy volunteers and 25 GBM patients. To delve into the microbial content, we employed PCR-DGGE, targeting the V3 region of the 16S rRNA gene, and conducted qPCR to measure the levels of crucial intestinal bacteria. For a more in-depth analysis, high-throughput sequencing was performed on a selection of 20 random faecal samples (10 from healthy individuals and 10 from GBM patients), targeting the V3+V4 region of the 16S rRNA gene. Our findings from examining the richness and diversity of the gut microbiota unveiled that GBM patients exhibited significantly higher microbial diversity compared to healthy individuals. At the phylum level, Proteobacteria saw a significant increase, while experienced a noteworthy decrease in the GBM group. Moving down to the family level, we observed significantly elevated levels of , , and in GBM patients, while levels of , , and were notably lower. Delving into genera statistics, we noted a substantial increase in the abundance of , , and , alongside significantly lower levels of , , and in the GBM group compared to the control group. Furthermore, when examining specific species, we found a significant increase in and in the GBM group. These observations collectively indicate a marked dysbiosis in the gut microbial composition of GBM patients. Additionally, the GBM group exhibited notably higher levels of alpha diversity when compared to the control group. This increase in diversity suggests a significant bacterial overgrowth in the gut of GBM patients in contrast to the controls. As a result, this research opens up potential avenues to gain a better understanding of the underlying mechanisms, pathways, and potential treatments for GBM, stemming from the significant implications of gut microbial dysbiosis in these patients.
PubMed: 38756585
DOI: 10.1016/j.heliyon.2024.e30494 -
PloS One 2024Dysbiosis during childhood impacts the configuration and maturation of the microbiota. The immaturity of the infant microbiota is linked with the development of...
BACKGROUND
Dysbiosis during childhood impacts the configuration and maturation of the microbiota. The immaturity of the infant microbiota is linked with the development of inflammatory, allergic, and dysmetabolic diseases.
AIMS
To identify taxonomic changes associated with age and GDM and classify the maturity of the intestinal microbiota of children of mothers with GDM and children without GDM (n-GDM).
METHODS
Next-generation sequencing was used to analyze the V3-V4 region of 16S rRNA gene. QIIME2 and Picrust2 were used to determine the difference in the relative abundance of bacterial genera between the study groups and to predict the functional profile of the intestinal microbiota.
RESULTS
According to age, the older GDM groups showed a lower alpha diversity and different abundance of Enterobacteriaceae, Veillonella, Clostridiales, and Bacteroides. Regarding the functional profile, PWY-7377 and K05895 associated with Vitamin B12 metabolism were reduced in GDM groups. Compared to n-GDM group, GDM offspring had microbiota immaturity as age-discriminatory taxa in random forest failed to classify GDM offspring according to developmental age (OOB error 81%). Conclusion. Offspring from mothers with GDM have a distinctive taxonomic profile related to taxa associated with gut microbiota immaturity.
Topics: Humans; Diabetes, Gestational; Gastrointestinal Microbiome; Female; Pregnancy; Bacteroides; RNA, Ribosomal, 16S; Veillonella; Infant; Adult; Male; Dysbiosis; Feces; Child, Preschool; High-Throughput Nucleotide Sequencing
PubMed: 38743706
DOI: 10.1371/journal.pone.0302726 -
The Veterinary Quarterly Dec 2024The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in...
The gut microbiota (GM) is essential for mammalian health. Although the association between infant GM and breast milk (BM) composition has been well established in humans, such a relationship has not been investigated in horses. Hence, this study was conducted to analyze the GM formation of foals during lactation and determine the presence of low-molecular-weight metabolites in mares' BM and their role in shaping foals' GM. The fecal and BM samples from six pairs of foals and mares were subjected to 16S ribosomal RNA metagenomic and metabolomic analyses, respectively. The composition of foal GM changed during lactation time; hierarchical cluster analysis divided the fetal GM into three groups corresponding to different time points in foal development. The level of most metabolites in milk decreased over time with increasing milk yield, while threonic acid and ascorbic acid increased. Further analyses revealed gut bacteria that correlated with changes in milk metabolites; for instance, there was a positive correlation between in the foal's gut microbiota and serine/glycine in the mother's milk. These findings help improve the rearing environment of lactating horses and establish artificial feeding methods for foals.
Topics: Animals; Gastrointestinal Microbiome; Horses; Female; Milk; Feces; Animals, Newborn; RNA, Ribosomal, 16S; Lactation
PubMed: 38733121
DOI: 10.1080/01652176.2024.2349948 -
International Journal of Molecular... Apr 2024(), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the...
(), a Gram-negative oral pathogen, promotes and accelerates periodontitis-associated gut disorders. Intestinal epithelial barrier dysfunction is crucial in the pathogenesis of intestinal and systemic diseases. In this study, we sought to elucidate the protective role of cinnamaldehyde (CNM, an activator of Nrf2) against (W83) and -derived lipopolysaccharide (-LPS) induced intestinal epithelial barrier dysfunction via antioxidative mechanisms in IEC-6 cells. IEC-6 (ATCC, CRL-1592) cells were pretreated with or without CNM (100 µM), in the presence or absence of (strain W83, 10 MOI) or -LPS (1, 10, and 100 µg/mL), respectively, between 0-72 h time points by adopting a co-culture method. Intestinal barrier function, cytokine secretion, and intestinal oxidative stress protein markers were analyzed. or -LPS significantly ( < 0.05) increased reactive oxygen species (ROS) and malondialdehyde (MDA) levels expressing oxidative stress damage. -LPS, as well as alone, induces inflammatory cytokines via TLR-4 signaling. Furthermore, infection reduced Nrf2 and NAD(P)H quinone dehydrogenase 1 (NQO1). Interestingly, inducible nitric oxide synthase (iNOS) protein expression significantly ( < 0.05) increased with -LPS or infection, with elevated levels of nitric oxide (NO). CNM treatment suppressed both - and -LPS-induced intestinal oxidative stress damage by reducing ROS, MDA, and NO production. Furthermore, CNM treatment significantly upregulated the expression of tight junction proteins via increasing the phosphorylation levels of PI3K/Akt/Nrf2 suppressing inflammatory cytokines. CNM protected against infection-induced intestinal epithelial barrier dysfunction by activating the PI3K/Akt-mediated Nrf2 signaling pathway in IEC-6 cells.
Topics: NF-E2-Related Factor 2; Acrolein; Animals; Signal Transduction; Proto-Oncogene Proteins c-akt; Rats; Porphyromonas gingivalis; Phosphatidylinositol 3-Kinases; Intestinal Mucosa; Nitric Oxide; Cell Line; Lipopolysaccharides; Oxidative Stress; Epithelial Cells; Toll-Like Receptor 4; Reactive Oxygen Species; Cytokines
PubMed: 38731952
DOI: 10.3390/ijms25094734 -
International Journal of Molecular... Apr 2024This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency:...
This study explores the impact of defecation frequency on the gut microbiome structure by analyzing fecal samples from individuals categorized by defecation frequency: infrequent (1-3 times/week, = 4), mid-frequent (4-6 times/week, = 7), and frequent (daily, = 9). Utilizing 16S gene-based sequencing and LC-MS/MS metabolome profiling, significant differences in microbial diversity and community structures among the groups were observed. The infrequent group showed higher microbial diversity, with community structures significantly varying with defecation frequency, a pattern consistent across all sampling time points. The genus was predominant in the infrequent group, but decreased with more frequent defecation, while the genus was more common in the frequent group, decreasing as defecation frequency lessened. The infrequent group demonstrated enriched biosynthesis genes for aromatic amino acids and branched-chain amino acids (BCAAs), in contrast to the frequent group, which had a higher prevalence of genes for BCAA catabolism. Metabolome analysis revealed higher levels of metabolites derived from aromatic amino acids and BCAA metabolism in the infrequent group, and lower levels of BCAA-derived metabolites in the frequent group, consistent with their predicted metagenomic functions. These findings underscore the importance of considering stool consistency/frequency in understanding the factors influencing the gut microbiome.
Topics: Gastrointestinal Microbiome; Humans; RNA, Ribosomal, 16S; Feces; Male; Adult; Defecation; Female; Metabolome; Biodiversity; Amino Acids, Branched-Chain; Metabolomics; Bacteria; Bacteroides; Metagenome
PubMed: 38731876
DOI: 10.3390/ijms25094657 -
Gut Microbes 2024Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to...
Emerging evidence indicates that alteration of gut microbiota plays an important role in chronic kidney disease (CKD)-related vascular calcification (VC). We aimed to investigate the specific gut microbiota and the underlying mechanism involved in CKD-VC. We identified an increased abundance of () in the feces of CKD rats (induced by using 5/6 nephrectomy followed by a high calcium and phosphate diet) with aortic calcification via amplicon sequencing of 16S rRNA genes. In patients with CKD, we further confirmed a positive correlation between abundance of and aortic calcification scores. Moreover, oral administration of live aggravated CKD-related VC and osteogenic differentiation of vascular smooth muscle cells , accompanied by intestinal destruction, enhanced expression of Toll-like receptor-4 (TLR4), and elevated lipopolysaccharide (LPS) levels. and experiments consistently demonstrated that -derived LPS (-LPS) accelerated high phosphate-induced VC and VSMC osteogenic differentiation. Mechanistically, -LPS bound to TLR4, then activated the nuclear factor κB (NF-κB) and nucleotide-binding domain, leucine-rich-containing family, pyrin domain-containing-3 (NLRP3) inflammasome signals during VC. Inhibition of NF-κB reduced NLRP3 inflammasome and attenuated -LPS-induced VSMC calcification. Our study clarifies a novel role of in CKD-related VC, by the mechanisms involving increased inflammation-regulating metabolites including -LPS, and activation of the NF-κB/NLRP3 signaling pathway. These findings highlight and its-derived LPS as potential therapeutic targets for VC in CKD.
Topics: Animals; Vascular Calcification; NF-kappa B; Lipopolysaccharides; Rats; Renal Insufficiency, Chronic; Signal Transduction; Humans; Male; Toll-Like Receptor 4; Gastrointestinal Microbiome; Prevotella; Rats, Sprague-Dawley; Myocytes, Smooth Muscle; Osteogenesis; Muscle, Smooth, Vascular; NLR Family, Pyrin Domain-Containing 3 Protein; Feces; Inflammasomes
PubMed: 38727248
DOI: 10.1080/19490976.2024.2351532 -
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 -
PeerJ 2024Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. is a...
BACKGROUND
Periodontitis is a chronic infectious disease, characterized by an exacerbated inflammatory response and a progressive loss of the supporting tissues of the teeth. is a key etiologic agent in periodontitis. Cystatin C is an antimicrobial salivary peptide that inhibits the growth of . This study aimed to evaluate the antimicrobial activity of this peptide and its effect on cytokine production, nitric oxide (NO) release, reactive oxygen species (ROS) production, and programmed cell death in human macrophages infected with
METHODS
Monocyte-derived macrophages generated from peripheral blood were infected with (MOI 1:10) and stimulated with cystatin C (2.75 µg/ml) for 24 h. The intracellular localization of and cystatin C was determined by immunofluorescence and transmission electron microscopy (TEM). The intracellular antimicrobial activity of cystatin C in macrophages was assessed by counting Colony Forming Units (CFU). ELISA assay was performed to assess inflammatory (TNFα, IL-1β) and anti-inflammatory (IL-10) cytokines. The production of nitrites and ROS was analyzed by Griess reaction and incubation with 2',7'-dichlorodihydrofluorescein diacetate (HDCFDA), respectively. Programmed cell death was assessed with the TUNEL assay, Annexin-V, and caspase activity was also determined.
RESULTS
Our results showed that cystatin C inhibits the extracellular growth of . In addition, this peptide is internalized in the infected macrophage, decreases the intracellular bacterial load, and reduces the production of inflammatory cytokines and NO. Interestingly, peptide treatment increased ROS production and substantially decreased bacterial-induced macrophage apoptosis.
CONCLUSIONS
Cystatin C has antimicrobial and immuno-regulatory activity in macrophages infected with These findings highlight the importance of understanding the properties of cystatin C for its possible therapeutic use against oral infections such as periodontitis.
Topics: Porphyromonas gingivalis; Humans; Macrophages; Cystatin C; Reactive Oxygen Species; Nitric Oxide; Cytokines; Periodontitis; Apoptosis
PubMed: 38708345
DOI: 10.7717/peerj.17252 -
Clinical and Experimental Dental... Jun 2024Periodontal inflammation may be assessed by bleeding on probing and subgingival temperature. This pilot study evaluated the intrapatient relationship between subgingival...
OBJECTIVES
Periodontal inflammation may be assessed by bleeding on probing and subgingival temperature. This pilot study evaluated the intrapatient relationship between subgingival temperature and selected bacterial groups/species in deep periodontal pockets with bleeding on probing.
MATERIALS AND METHODS
In each of eight adults, an electronic temperature probe identified three "hot" pockets with elevated subgingival temperature and three "cool" pockets with normal subgingival temperature among premolars/molars with 6‒10 mm probing depths and bleeding on probing. Microbial samples collected separately from the hot and cool periodontal pockets were cultured for selected periodontal pathogens.
RESULTS
Hot compared to cool periodontal pockets revealed significantly higher absolute and normalized subgingival temperatures and yielded higher mean proportions of Porphyromonas gingivalis (10.2% for hot vs. 2.5% for cool, p = 0.030) and total red/orange complex periodontal pathogens (48.0% for hot vs. 24.6% for cool, p = 0.012).
CONCLUSIONS
Hot versus cool deep periodontal pockets harbored significantly higher levels of major periodontal pathogens. Subgingival temperature measurements may potentially be useful to assess risk of periodontitis progression and the efficacy of periodontal therapy.
Topics: Humans; Male; Female; Pilot Projects; Middle Aged; Periodontal Pocket; Porphyromonas gingivalis; Adult; Periodontitis; Body Temperature; Bacterial Load; Gingiva; Aged
PubMed: 38706420
DOI: 10.1002/cre2.891