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Microbiome Oct 2023Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an...
BACKGROUND
Like its human counterpart, canine atopic dermatitis (cAD) is a chronic relapsing condition; thus, most cAD-affected dogs will require lifelong treatment to maintain an acceptable quality of life. A potential intervention is modulation of the composition of gut microbiota, and in fact, probiotic treatment has been proposed and tried in human atopic dermatitis (AD) patients. Since dogs are currently receiving intensive medical care, this will be the same option for dogs, while evidence of gut dysbiosis in cAD is still missing, although skin microbial profiling in cAD has been conducted in several studies. Therefore, we conducted a comprehensive analysis of both gut and skin microbiota in cAD in one specific cAD-predisposed breed, Shiba Inu. Additionally, we evaluated the impact of commonly used medical management on cAD (Janus kinase; JAK inhibitor, oclacitinib) on the gut and skin microbiota. Furthermore, we genotyped the Shiba Inu dogs according to the mitochondrial DNA haplogroup and assessed its association with the composition of the gut microbiota.
RESULTS
Staphylococcus was the most predominant bacterial genus observed in the skin; Escherichia/Shigella and Clostridium sensu stricto were highly abundant in the gut of cAD-affected dogs. In the gut microbiota, Fusobacteria and Megamonas were highly abundant in healthy dogs but significantly reduced in cAD-affected dogs. The abundance of these bacterial taxa was positively correlated with the effect of the treatment and state of the disease. Oclacitinib treatment on cAD-affected dogs shifted the composition of microbiota towards that in healthy dogs, and the latter brought it much closer to healthy microbiota, particularly in the gut. Additionally, even within the same dog breed, the mtDNA haplogroup varied, and there was an association between the mtDNA haplogroup and microbial composition in the gut and skin.
CONCLUSIONS
Dysbiosis of both the skin and the gut was observed in cAD in Shiba Inu dogs. Our findings provide a basis for the potential treatment of cAD by manipulating the gut microbiota as well as the skin microbiota. Video Abstract.
Topics: Dogs; Humans; Animals; Dermatitis, Atopic; Dysbiosis; Quality of Life; Microbiota; Bacteria; DNA, Mitochondrial
PubMed: 37864204
DOI: 10.1186/s40168-023-01671-2 -
Archives of Oral Biology Oct 2023The present study aims to investigate the variations in dental caries (DC) related microbiome abnormality and metabolomics shift in children.
OBJECTIVE
The present study aims to investigate the variations in dental caries (DC) related microbiome abnormality and metabolomics shift in children.
DESIGN
The patients were divided into two groups healthy control (C) and highly affected DC children based on inclusion and exclusion criteria. Saliva samples were collected and used for the taxonomic and functional characterization of oral microbiota.
RESULTS
Metatranscriptomics analysis revealed the alterations and composition of oral microbiota in the C and DC groups. Relative abundance in the C group was associated with Firmicutes, Actinobacteria, and Bacteroidetes. Whereas, the microbial composition in the DC group was found to be considerably altered with increases in the abundance of the Proteobacteria (25%), Fusobacteria (15%), and Cyanobacteria (8%) while decreases in the abundance of Firmicutes (10%) and Bacteroidetes (23%). Alterations in the phylum composition were positively and negatively correlated with several metabolites of sugars (such as fructose, sorbose, ribose, allose, and mannose) and amino acids (such as arginine, lysine, tryptophan, and proline). Moreover, in comparison with the C group, the metabolic shift of the DC group was different with an increase in certain tricarboxylic acid cycle intermediates levels, and a decrease in fatty acid. Such alterations can enhance the growth of oral pathogens and contribute to DC development.
CONCLUSIONS
The findings of this study suggest that an altered abundance of Actinobacillus, Fusobacterium, and Shuttleworthia can serve as biomarkers of DC in children.
Topics: Humans; Child; Dental Caries; RNA, Ribosomal, 16S; Bacteria; Microbiota; Actinobacteria; Fusobacterium
PubMed: 37540967
DOI: 10.1016/j.archoralbio.2023.105776 -
Scientific Reports Oct 2023
PubMed: 37903834
DOI: 10.1038/s41598-023-44593-7 -
Journal of the American Chemical Society Dec 2023Immunotherapy of triple-negative breast cancer (TNBC) has an unsatisfactory therapeutic outcome due to an immunologically "cold" microenvironment. () was found to be...
Immunotherapy of triple-negative breast cancer (TNBC) has an unsatisfactory therapeutic outcome due to an immunologically "cold" microenvironment. () was found to be colonized in triple-negative breast tumors and was responsible for the immunosuppressive tumor microenvironment and tumor metastasis. Herein, we constructed a bacteria-derived outer membrane vesicle (OMV)-coated nanoplatform that precisely targeted tumor tissues for dual killing of and cancer cells, thus transforming intratumor bacteria into immunopotentiators in immunotherapy of TNBC. The as-prepared nanoparticles efficiently induced immunogenic cell death through a Fenton-like reaction, resulting in enhanced immunogenicity. Meanwhile, intratumoral was killed by metronidazole, resulting in the release of pathogen-associated molecular patterns (PAMPs). PAMPs cooperated with OMVs further facilitated the maturation of dendritic cells and subsequent T-cell infiltration. As a result, the "kill two birds with one stone" strategy warmed up the cold tumor environment, maximized the antitumor immune response, and achieved efficient therapy of TNBC as well as metastasis prevention. Overall, this strategy based on a microecology distinction in tumor and normal tissue as well as microbiome-induced reversal of cold tumors provides new insight into the precise and efficient immune therapy of TNBC.
Topics: Humans; Triple Negative Breast Neoplasms; Adjuvants, Immunologic; Pathogen-Associated Molecular Pattern Molecules; Immunotherapy; Fusobacterium nucleatum; Cell Line, Tumor; Tumor Microenvironment
PubMed: 37987621
DOI: 10.1021/jacs.3c09472 -
Gut Microbes Dec 2023As with many diseases, tumor formation in colorectal cancer (CRC) is multifactorial and involves immune, environmental factors and various genetics that contribute to...
As with many diseases, tumor formation in colorectal cancer (CRC) is multifactorial and involves immune, environmental factors and various genetics that contribute to disease development. Accumulating evidence suggests that the gut microbiome is linked to the occurrence and development of CRC, and these microorganisms are important for immune maturation. However, a systematic perspective integrating microbial profiling, T cell receptor (TCR) and somatic mutations in humans with CRC is lacking. Here, we report distinct features of the expressed TCRβ repertoires in the peripheral blood of and CRC patients ( = 107) and healthy donors ( = 30). CRC patients have elevated numbers of large TCRβ clones and they have very low TCR diversity. The metagenomic sequencing data showed that the relative abundance of (), and were elevated consistently in CRC patients ( = 97) compared to HC individuals ( = 30). The abundance of and was reduced in CRC ( = 97) compared to HC ( = 30). The correlation between somatic mutations of target genes (16 genes, = 79) and TCR clonality and microbial biomarkers in CRC had been investigated. Importantly, we constructed a random forest classifier (contains 15 features) based on microbiome and TCR repertoires, which can be used as a clinical detection method to screen patients for CRC. We also analysis of -specific TCR repertoire characteristics. Collectively, our large-cohort multi-omics data aimed to identify novel biomarkers to inform clinical decision-making in the detection and diagnosis of CRC, which is of possible etiological and diagnostic significance.
Topics: Humans; Colorectal Neoplasms; Gastrointestinal Microbiome; Fusobacterium nucleatum; Biomarkers; Mutation; Receptors, Antigen, T-Cell
PubMed: 37795995
DOI: 10.1080/19490976.2023.2263934 -
Nature Communications Feb 2024Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of...
Fusobacterium nucleatum (F. nucleatum) promotes intestinal tumor growth and its relative abundance varies greatly among patients with CRC, suggesting the presence of unknown, individual-specific effectors in F. nucleatum-dependent carcinogenesis. Here, we identify that F. nucleatum is enriched preferentially in KRAS p.G12D mutant CRC tumor tissues and contributes to colorectal tumorigenesis in Villin-Cre/Kras mice. Additionally, Parabacteroides distasonis (P. distasonis) competes with F. nucleatum in the G12D mouse model and human CRC tissues with the KRAS mutation. Orally gavaged P. distasonis in mice alleviates the F. nucleatum-dependent CRC progression. F. nucleatum invades intestinal epithelial cells and binds to DHX15, a protein of RNA helicase family expressed on CRC tumor cells, mechanistically involving ERK/STAT3 signaling. Knock out of Dhx15 in Villin-Cre/Kras mice attenuates the CRC phenotype. These findings reveal that the oncogenic effect of F. nucleatum depends on somatic genetics and gut microbial ecology and indicate that personalized modulation of the gut microbiota may provide a more targeted strategy for CRC treatment.
Topics: Animals; Humans; Mice; Carcinogenesis; Colorectal Neoplasms; Fusobacterium nucleatum; Proto-Oncogene Proteins p21(ras); RNA Helicases
PubMed: 38402201
DOI: 10.1038/s41467-024-45572-w -
Microbiome Nov 2023The mechanism of microbiota assembly is one of the main problems in microbiome research, which is also the primary theoretical basis for precise manipulation of...
BACKGROUND
The mechanism of microbiota assembly is one of the main problems in microbiome research, which is also the primary theoretical basis for precise manipulation of microbial communities. Bacterial quorum sensing (QS), as the most common means for bacteria to exchange information and interactions, is characterized by universality, specificity, and regulatory power, which therefore may influence the assembly processes of human microbiota. However, the regulating role of QS in microbiota assembly is rarely reported. In this study, we developed an optimized in vitro oral biofilm microbiota assembling (OBMA) model to simulate the time-series assembly of oral biofilm microbiota (OBM), by which to excavate the QS network and its regulating power in the process.
RESULTS
By using the optimized OBMA model, we were able to restore the assembly process of OBM and generate time-series OBM metagenomes of each day. We discovered a total of 2291 QS protein homologues related to 21 QS pathways. Most of these pathways were newly reported and sequentially enriched during OBM assembling. These QS pathways formed a comprehensive longitudinal QS network that included successively enriched QS hubs, such as Streptococcus, Veillonella-Megasphaera group, and Prevotella-Fusobacteria group, for information delivery. Bidirectional cross-talk among the QS hubs was found to play critical role in the directional turnover of microbiota structure, which in turn, influenced the assembly process. Subsequent QS-interfering experiments accurately predicted and experimentally verified the directional shaping power of the longitudinal QS network in the assembly process. As a result, the QS-interfered OBM exhibited delayed and fragile maturity with prolonged membership of Streptococcus and impeded membership of Prevotella and Fusobacterium.
CONCLUSION
Our results revealed an unprecedented longitudinal QS network during OBM assembly and experimentally verified its power in predicting and manipulating the assembling process. Our work provides a new perspective to uncover underlying mechanism in natural complex microbiota assembling and a theoretical basis for ultimately precisely manipulating human microbiota through intervention in the QS network. Video Abstract.
Topics: Humans; Quorum Sensing; Bacterial Proteins; Bacteria; Biofilms; Streptococcus; Microbiota
PubMed: 37926838
DOI: 10.1186/s40168-023-01699-4 -
Journal of Periodontology Sep 2023This study tests the effects of scaling and root planing (SRP) versus SRP plus minocycline hydrochloride microspheres (SRP+MM) on 11 periodontal pathogens and clinical... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study tests the effects of scaling and root planing (SRP) versus SRP plus minocycline hydrochloride microspheres (SRP+MM) on 11 periodontal pathogens and clinical outcomes in Stage II-IV Grade B periodontitis participants.
METHODS
Seventy participants were randomized to receive SRP (n = 35) or SRP+MM (n = 35). Saliva and clinical outcomes were collected for both groups at baseline before SRP, 1-month reevaluation, and at 3- and 6-month periodontal recall. MM were delivered to pockets ≥5 mm immediately after SRP and immediately after the 3-month periodontal maintenance in the SRP+MM group. A proprietary saliva test was utilized to quantitate 11 putative periodontal pathogens. Microorganisms and clinical outcomes were compared between groups using generalized linear mixed-effects models with fixed effects and random effects terms. Mean changes from baseline were compared between groups via group-by-visit interaction tests.
RESULTS
Significant reduction in Tannerella forsythia, Treponema denticola, Fusobacterium nucleatum, Prevotella intermedia, Parvimonas micra, and Eikenella corrodens were identified at the 1-month reevaluation after SRP+MM. Six months after SRP with a re-application of MM 3 months after SRP, Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, and Eikenella corrodens were significantly reduced. SRP+MM participants had significant clinical outcome reductions in pockets ≥5 mm at the reevaluation, 3- and 6-month periodontal maintenance, and clinical attachment loss gains at the 6-month periodontal maintenance.
CONCLUSION
MM delivered immediately after SRP and reapplication at 3 months appeared to contribute to improved clinical outcomes and sustained decreased numbers of Fusobacterium nucleatum, Prevotella intermedia, Campylobacter rectus, and Eikenella corrodens at 6 months.
Topics: Humans; Minocycline; Root Planing; Microspheres; Periodontal Pocket; Dental Scaling; Fusobacterium nucleatum; Prevotella intermedia; Eikenella corrodens; Follow-Up Studies; Periodontal Attachment Loss; Anti-Bacterial Agents
PubMed: 37191955
DOI: 10.1002/JPER.23-0002 -
Trends in Molecular Medicine Oct 2023Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with...
Recent work by Muraoka and colleagues reports that the Gram-negative anaerobic bacterium Fusobacterium nucleatum is detected in the uterus of 64% of women with endometriosis. Fusobacterium infection causes macrophage infiltration, transforming growth factor-β production, and transgelin upregulation in human and mouse endometria as well as endometriotic lesion development in a mouse model of endometriosis.
Topics: Animals; Mice; Female; Humans; Fusobacterium; Base Composition; Endometriosis; Phylogeny; RNA, Ribosomal, 16S; Sequence Analysis, DNA
PubMed: 37599125
DOI: 10.1016/j.molmed.2023.08.003 -
3 Biotech Sep 2023Gastroduodenal diseases have prevailed for a long time and more so due to dominance of gut bacteria in most of the cases. But habitation by other gut microbiota in... (Review)
Review
Gastroduodenal diseases have prevailed for a long time and more so due to dominance of gut bacteria in most of the cases. But habitation by other gut microbiota in gastroduodenal diseases and the relationship between and gastrointestinal microbiota in different gastroduodenal diseases is somewhat being unravelled in the current times. For this systematic review, we did a literature search of various gastroduodenal diseases and the effect on gut microbiota pertaining to it. A search of the online bibliographic databases PUBMED and PUBMED CENTRAL was carried out to identify articles published between 1977 and May 2022. The analysis of these selected studies highlighted the inhabitation of other gut microbiota such as , and many others. Interplay between these microbiota and have also been noted which suggested that gastroduodenal diseases and gut microbiota are intertwined by a symbiotic association regardless of the status. The relationship between the gut microbiota and many gastroduodenal diseases, such as gastritis, gastric cancer, lymphomas, and ulcers, demonstrates the dysbiosis of the gut microbiota in both the presence and absence of . The evolving ways for eliminating are provided along with inhibiting qualities of other species on . Most significant member of our gut system is which has been associated with numerous diseases like gastric cancer, gastritis, duodenal ulcer.
PubMed: 37588796
DOI: 10.1007/s13205-023-03734-5