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Microorganisms Apr 2023(1) Background: The human gut microbiome may regulate sleep through the gut-brain axis. However, the sleep-promoting effects of gut microbiota remain unclear. (2)...
(1) Background: The human gut microbiome may regulate sleep through the gut-brain axis. However, the sleep-promoting effects of gut microbiota remain unclear. (2) Methods: We obtained sleep-wake profiles from 25 rats receiving ( group), 5 rats receiving ( group), 4 rats not receiving bacteria (No administration group), and 8 rats receiving extracellular vesicles (EV) (EV group) during the baseline, administration, and withdrawal periods. (3) Results: The group showed increased total sleep, rapid eye movement (REM) sleep, and non-rapid eye movement (NREM) sleep time during the administration and withdrawal periods; on the last day of administration, we found significant increases of 52 min for total sleep ( < 0.01), 13 min for REM sleep ( < 0.05), and 39 min for NREM sleep ( < 0.01) over the baseline. EV administration also increased NREM sleep time on Day 3 of administration ( = 0.05). We observed a linear trend in the dose-response relationship for total sleep and NREM sleep in the group. However, neither the no-administration group nor the group showed significant findings. (4) Conclusions: Oral administration of probiotic may improve sleep and could be a potential sleep aid. Further rigorous evaluations for the safety and efficacy of supplementation are warranted.
PubMed: 37317125
DOI: 10.3390/microorganisms11051151 -
Frontiers in Immunology 2019Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that there is enrichment or depletion of some gut bacteria in... (Comparative Study)
Comparative Study
Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. We and others have shown that there is enrichment or depletion of some gut bacteria in MS patients compared to healthy controls (HC), suggesting an important role of the gut bacteria in disease pathogenesis. Thus, specific gut bacteria that are lower in abundance in MS patients could be used as a potential treatment option for this disease. In particular, we and others have shown that MS patients have a lower abundance of compared to HC, whereas the abundance of is increased in patients that receive disease-modifying therapies such as Copaxone® (Glatiramer acetate-GA). This inverse correlation between the severity of MS disease and the abundance of suggests its potential for use as a therapeutic option to treat MS. Notably we have previously identified a specific strain (), that suppresses disease in the animal model of MS, experimental autoimmune encephalomyelitis (EAE) compared with sham treatment. In the present study we analyzed whether the disease suppressing effects of synergize with those of the disease-modifying drug Copaxone® to more effectively suppress disease compared to either treatment alone. Treatment with was as effective in suppressing disease as treatment with Copaxone®, whereas the combination of plus Copaxone® was not more effective than either individual treatment. -treated mice had an increased frequency and number of CD4FoxP3 regulatory T cells in periphery as well as gut and a decreased frequency of pro-inflammatory IFN-γ and IL17-producing CD4 T cells in the CNS, suggesting suppresses disease by boosting anti-inflammatory immune responses and inhibiting pro-inflammatory immune responses. In conclusion, our study indicates that the human gut commensal can suppress disease as efficiently as Copaxone® and may provide an alternative treatment option for MS patients.
Topics: Animals; Brain; Encephalomyelitis, Autoimmune, Experimental; Gastrointestinal Microbiome; Glatiramer Acetate; HLA-DR3 Antigen; Humans; Immunosuppressive Agents; Mice, Transgenic; Multiple Sclerosis; Prevotella; Spinal Cord
PubMed: 30984162
DOI: 10.3389/fimmu.2019.00462 -
PloS One 2020Cystic Fibrosis (CF), caused by mutations affecting the CFTR gene, is characterised by viscid secretions in multiple organ systems. CF airways contain thick mucus,...
Cystic Fibrosis (CF), caused by mutations affecting the CFTR gene, is characterised by viscid secretions in multiple organ systems. CF airways contain thick mucus, creating a gradient of hypoxia, which promotes the establishment of polymicrobial infection. Such inflammation predisposes to further infection, a self-perpetuating cycle in mediated by NF-κB. Anaerobic Gram-negative Prevotella spp. are found in sputum from healthy volunteers and CF patients and in CF lungs correlate with reduced levels of inflammation. Prevotella histicola (P. histicola) can suppress murine lung inflammation, however, no studies have examined the role of P. histicola in modulating infection and inflammation in the CF airways. We investigated innate immune signalling and NF-kB activation in CF epithelial cells CFBE41o- in response to clinical stains of P. histicola and Pseudomonas aeruginosa (P. aeruginosa). Toll-Like Receptor (TLR) expressing HEK-293 cells and siRNA assays for TLRs and IKKα were used to confirm signalling pathways. We show that P. histicola infection activated the alternative NF-kB signalling pathway in CF bronchial epithelial cells inducing HIF-1α protein. TLR5 signalling was responsible for the induction of the alternative NF-kB pathway through phosphorylation of IKKα. The induction of transcription factor HIF-1α was inversely associated with the induction of the alternative NF-kB pathway and knockdown of IKKα partially restored canonical NF-kB activation in response to P. histicola. This study demonstrates that different bacterial species in the respiratory microbiome can contribute differently to inflammation, either by activating inflammatory cascades (P. aeruginosa) or by muting the inflammatory response by modulating similar or related pathways (P. histicola). Further work is required to assess the complex interactions of the lung microbiome in response to mixed bacterial infections and their effects in people with CF.
Topics: Bronchi; Cystic Fibrosis; Epithelial Cells; Humans; Interleukin-8; NF-kappa B; Prevotella; Pseudomonas Infections; Pseudomonas aeruginosa; Signal Transduction; Toll-Like Receptors
PubMed: 33031374
DOI: 10.1371/journal.pone.0235803 -
BMC Microbiology Jan 2022Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition...
BACKGROUND
Type 1 diabetes (T1D) is an autoimmune disease that is increasing in prevalence worldwide. One of the contributing factors to the pathogenesis of T1D is the composition of the intestinal microbiota, as has been demonstrated. in T1D patients, with some studies demonstrating a deficiency in their levels of Prevotella. We have isolated a strain of Prevotella histicola from a duodenal biopsy that has anti-inflammatory properties, and in addition, alters the development of autoimmune diseases in mouse models. Therefore, our hypothesis is that the oral administration of P. histicola might delay the development of T1D in the non-obese diabetic (NOD) mice. To assess this, we used the following materials and methods. Female NOD mice (ages 5-8 weeks) were administered every other day P. histicola that was cultured in-house. Blood glucose levels were measured every other week. Mice were sacrificed at various time points for histopathological analysis of the pancreas. Modulation of immune response by the commensal was tested by analyzing regulatory T-cells and NKp46+ cells using flow cytometry and intestinal cytokine mRNA transcript levels using quantitative RT-PCR. For microbial composition, 16 s rRNA gene analysis was conducted on stool samples collected at various time points.
RESULTS
Administration of P. histicola in NOD mice delayed the onset of T1D. Beta diversity in the fecal microbiomes demonstrated that the microbial composition of the mice administered P. histicola was different from those that were not treated. Treatment with P. histicola led to a significant increase in regulatory T cells with a concomitant decrease in NKp46+ cells in the pancreatic lymph nodes as compared to the untreated group after 5 weeks of treatment.
CONCLUSIONS
These observations suggest that P. histicola treatment delayed onset of diabetes by increasing the levels of regulatory T cells in the pancreatic lymph nodes. This preliminary work supports the rationale that enteral exposure to a non pathogenic commensal P. histicola be tested as a future therapy for T1D.
Topics: Animals; Bacteria; Cytokines; Diabetes Mellitus, Type 1; Duodenum; Feces; Female; Gastrointestinal Microbiome; Humans; Mice; Mice, Inbred NOD; Pancreas; Prevotella; Probiotics
PubMed: 34983374
DOI: 10.1186/s12866-021-02406-9 -
Arthritis & Rheumatology (Hoboken, N.J.) Dec 2016The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of...
OBJECTIVE
The gut microbiome regulates host immune homeostasis. Rheumatoid arthritis (RA) is associated with intestinal dysbiosis. This study was undertaken to test the ability of a human gut-derived commensal to modulate immune response and treat arthritis in a humanized mouse model.
METHODS
We isolated a commensal bacterium, Prevotella histicola, that is native to the human gut and has systemic immune effects when administered enterally. Arthritis-susceptible HLA-DQ8 mice were immunized with type II collagen and treated with P histicola. Disease incidence, onset, and severity were monitored. Changes in gut epithelial proteins and immune response as well as systemic cellular and humoral immune responses were studied in treated mice.
RESULTS
When treated with P histicola in prophylactic or therapeutic protocols, DQ8 mice exhibited significantly decreased incidence and severity of arthritis compared to controls. The microbial mucosal modulation of arthritis was dependent on regulation by CD103+ dendritic cells and myeloid suppressors (CD11b+Gr-1+ cells) and by generation of Treg cells (CD4+CD25+FoxP3+) in the gut, resulting in suppression of antigen-specific Th17 responses and increased transcription of interleukin-10. Treatment with P histicola led to reduced intestinal permeability by increasing expression of enzymes that produce antimicrobial peptides as well as tight junction proteins (zonula occludens 1 and occludin). However, the innate immune response via Toll-like receptor 4 (TLR-4) and TLR-9 was not affected in treated mice.
CONCLUSION
Our results demonstrate that enteral exposure to P histicola suppresses arthritis via mucosal regulation. P histicola is a unique commensal that can be explored as a novel therapy for RA and may have few or no side effects.
Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Cell Proliferation; Chemokines; Cytokines; Dendritic Cells; Flow Cytometry; Gastrointestinal Microbiome; HLA-DQ Antigens; Humans; Interleukin-10; Intestinal Mucosa; Intestines; Mice; Mice, Transgenic; Occludin; Permeability; Prevotella; Prevotella melaninogenica; RNA, Messenger; Reverse Transcriptase Polymerase Chain Reaction; T-Lymphocytes, Regulatory; Th17 Cells; Toll-Like Receptor 4; Toll-Like Receptor 9; Zonula Occludens-1 Protein
PubMed: 27337150
DOI: 10.1002/art.39785 -
BMC Veterinary Research Oct 2021Prevotella histicola is a facultative oral pathogen that under certain conditions causes pathologies such as caries and periodontitis in humans. Prevotella spp. also...
BACKGROUND
Prevotella histicola is a facultative oral pathogen that under certain conditions causes pathologies such as caries and periodontitis in humans. Prevotella spp. also colonize the oral cavity of horses and can cause disease, but P. histicola has not yet been identified.
CASE PRESENTATION
A 12-year-old Tinker mare was referred to the clinic for persistent, malodorous purulent nasal discharge and quidding. Conservative antibiotic (penicillin), antiphlogistic (meloxicam), and mucolytic (dembrexine-hydrochloride) treatment prior to referral was unsuccessful and symptoms worsened. Oral examination, radiography, sino-/ rhinoscopy, and standing computed tomography revealed severe apical/ periapical infection of the upper cheek tooth 209 with accompanying unilateral sinonasal inflammation and conchal necrosis. The tooth exhibited extensive subocclusal mesial infundibular cemental hypoplasia and caries, and an occlusal fissure fracture. After mechanical debridement and thermoplastic resin filling of the spacious subocclusal carious infundibular lesion, the tooth was extracted intraorally. The sinusitis and conchal necrosis were treated transendoscopically. Selective bacteriological swab cultures of affected tooth roots and subsequent matrix-assisted laser desorption ionization-time of flight mass spectrometry showed an infection with the obligate anaerobic, Gram-negative bacterium P. histicola. Surgical intervention and adapted antibiotic therapy led to normal healing without complications.
CONCLUSIONS
This study provides the first documented case of dental infection in a horse caused by P. histicola at once indicating necessity of more sufficient microbiological diagnostics and targeted antibiotic treatment in equine dental practice. This finding is also conducive to understand species-specific Prevotella diversity and cross-species distribution.
Topics: Animals; Bacteroidaceae Infections; Cheek; Female; Horse Diseases; Horses; Humans; Prevotella; Tomography, X-Ray Computed; Tooth; Tooth Extraction; Treatment Outcome
PubMed: 34717609
DOI: 10.1186/s12917-021-03048-9 -
Environmental Toxicology and... Jun 2023The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate...
The widespread use of glyphosate, a broad-spectrum herbicide, has resulted in significant human exposure, and recent studies have challenged the notion that glyphosate is safe for humans. Although the link between disease states and glyphosate exposure is increasingly appreciated, the mechanistic links between glyphosate and its toxic effects on human health are poorly understood. Recent studies have suggested that glyphosate may cause toxicity through modulation of the gut microbiome, but evidence for glyphosate-induced gut dysbiosis and its effect on host physiology at doses approximating the U.S. Acceptable Daily Intake (ADI = 1.75 mg/kg body weight) is limited. Here, utilizing shotgun metagenomic sequencing of fecal samples from C57BL/6 J mice, we show that glyphosate exposure at doses approximating the U.S. ADI significantly impacts gut microbiota composition. These gut microbial alterations were associated with effects on gut homeostasis characterized by increased proinflammatory CD4IL17A T cells and Lipocalin-2, a known marker of intestinal inflammation.
Topics: Mice; Humans; Animals; Gastrointestinal Microbiome; Mice, Inbred C57BL; Herbicides; Homeostasis; Glyphosate
PubMed: 37196884
DOI: 10.1016/j.etap.2023.104149 -
International Journal of Molecular... Feb 2023The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and...
The role of dysbiosis in the development and progression of oral potentially malignant disorders (OPMDs) remains largely unknown. Here, we aim to characterize and compare the oral microbiome of homogeneous leucoplakia (HL), proliferative verrucous leukoplakia (PVL), oral squamous cell carcinoma (OSCC), and OSCC preceded by PVL (PVL-OSCC). Fifty oral biopsies from HL ( = 9), PVL ( = 12), OSCC ( = 10), PVL-OSCC ( = 8), and healthy ( = 11) donors were obtained. The sequence of the V3-V4 region of the 16S rRNA gene was used to analyze the composition and diversity of bacterial populations. In the cancer patients, the number of observed amplicon sequence variants (ASVs) was lower and constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of and lower than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in , , , , , and ; PVL is enriched in , and ; OSCC is enriched in , and ; and PVL-OSCC is enriched in , and . There is differential dysbiosis in patients suffering from OPMDs and cancer. To the best of our knowledge, this is the first study comparing the oral microbiome alterations in these groups; thus, additional studies are needed.
Topics: Humans; Mouth Neoplasms; Carcinoma, Squamous Cell; Dysbiosis; RNA, Ribosomal, 16S; Leukoplakia, Oral; Microbiota
PubMed: 36834903
DOI: 10.3390/ijms24043466 -
Research (Washington, D.C.) 2022The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the...
The human oral microbiome correlates with numerous diseases, including lung cancer. Identifying the functional changes by metaproteomics helps understand the disease-related dysbiosis, yet characterizing low-abundant bacteria is challenging. Here, we developed a free-flow isoelectric focusing electrophoresis-mass spectrometry- (FFIEF-MS-) based metaproteomics strategy to reduce host interferences and enrich low-abundant bacteria for in-depth interpretation of the oral microbiome. With our method, the number of interfering peptides decreased by 52.87%, whereas the bacterial peptides and species increased by 94.97% and 44.90%, respectively, compared to the conventional metaproteomics approach. We identified 3647 bacterial proteins, which is the most comprehensive oral metaproteomics study to date. Lung cancer-associated bacteria were validated among an independent cohort. The imbalanced and and their dysregulated functions in inhibiting immune response and maintaining cell redox homeostasis were revealed. The FFIEF-MS may serve as a valuable strategy to study the mechanisms between human diseases and microbiomes with broader applications.
PubMed: 36320634
DOI: 10.34133/2022/9781578 -
Synthetic and Systems Biotechnology Sep 2021SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between...
SARS-CoV-2, the causative agent for COVID-19, infect human mainly via respiratory tract, which is heavily inhabited by local microbiota. However, the interaction between SARS-CoV-2 and nasopharyngeal microbiota, and the association with metabolome has not been well characterized. Here, metabolomic analysis of blood, urine, and nasopharyngeal swabs from a group of COVID-19 and non-COVID-19 patients, and metagenomic analysis of pharyngeal samples were used to identify the key features of COVID-19. Results showed lactic acid, l-proline, and chlorogenic acid methyl ester (CME) were significantly reduced in the sera of COVID-19 patients compared with non-COVID-19 ones. Nasopharyngeal commensal bacteria including , and were notably depleted in the pharynges of COVID-19 patients, while , , and were relatively increased. The abundance of and were significantly positively associated with serum CME, which might be an anti-SARS-CoV-2 bacterial metabolite. This study provides important information to explore the linkage between nasopharyngeal microbiota and disease susceptibility. The findings were based on a very limited number of patients enrolled in this study; a larger size of cohort will be appreciated for further investigation.
PubMed: 34151035
DOI: 10.1016/j.synbio.2021.06.002