Prevotella Histicola Research Articles

Probing the oral-brain connection: oral microbiome patterns in a large community cohort with anxiety, depression, and trauma symptoms, and periodontal outcomes

The role of the oral microbiome in mental health has recently been appreciated within the proposed oral-brain axis. This study examined the structure and composition of the salivary microbiome in a large-scale population-based cohort of individuals reporting mental health symptoms (n = 306) compared to mentally healthy controls (n = 164) using 16S rRNA sequencing. Mental health symptoms were evaluated using validated questionnaires and included depression, anxiety, and posttraumatic stress disorder (PTSD), with accompanying periodontal outcomes. Participants also indicated current or previous diagnoses of anxiety, depression, periodontitis, and gingivitis. Mental and periodontal health variables influenced the overall composition of the oral microbiome. PTSD symptoms correlated with a lower clr-transformed relative abundance of Haemophilus sputorum and a higher clr-transformed relative abundance of Prevotella histicola. The clr-transformed relative abundance of P. histicola was also positively associated with depressive scores and negatively associated with psychological quality of life. Anxiety disorder diagnosis was associated with a lower clr-transformed relative abundance of Neisseria elongate and a higher clr-transformed relative abundance of Oribacterium asaccharolyticum. A higher clr-transformed relative abundance of Shuttleworthia and lower clr-transformed relative abundance of Capnocytophaga were evident in those who reported a clinical periodontitis diagnosis. Higher Eggerthia and lower Haemophilus parainfluenzae clr-transformed relative abundances were associated with reported clinical periodontitis diagnoses and psychotherapeutic efficacy. Functional prediction analysis revealed a potential role for tryptophan metabolism/degradation in the oral-brain axis, which was confirmed by lower plasma serotonin levels across symptomatic groups. This study sheds light on the intricate interplay between oral microbiota, periodontal and mental health outcomes, and a potential role for tryptophan metabolism in the proposed oral-brain axis, emphasizing the need for further exploration to pave the way for novel therapeutic interventions and predicting therapeutic response.

The Association of the Oral Microbiota with Cognitive Functioning in Adolescence.

Background: A growing body of research supports the role of the microbial communities residing in the digestive system in the host's cognitive functioning. Most of these studies have been focused on the gut microbiome and its association with clinical phenotypes in middle-aged and older adults. There is an insufficiency of population-based research exploring the association of normative cognitive functioning with the microbiome particularly with the oral microbiota. Methods: In this study, using metagenomics and metabolomics, we characterized the salivary microbiome diversity in a sample of 51 males of Hispanic and African American origin aged 12-18 years and explored the associations between the microbiome and the youths' cognitive performance captured with the Kaufman Assessment Battery for Children II (KABC-II). Results: Several bacterial species of the oral microbiota and related metabolic pathways were associated with cognitive function. In particular, we found negative associations between indicators of general intelligence and the relative abundance of Bacteroidetes and Lachnospiraceae and positive associations with Bifidobacteriaceae and Prevotella histicola sp. Among metabolic pathways, the super pathways related to bacterial cell division and GABA metabolism were linked to cognitive function. Conclusions: The results of our work are consistent with the literature reporting on the association between microbiota and cognitive function and support further population work to elucidate the potential for a healthy oral microbiome to improve cognitive health.

The salivary virome during childhood dental caries.

While many studies have examined the bacterial taxa associated with dental caries, the most common chronic infectious disease globally, little is known about the caries-associated virome. In this study, the salivary viromes of 21 children with severe caries (>2 dentin lesions) and 23 children with healthy dentition were examined. 2,485 viral metagenome-assembled genomes (vMAGs) were identified, binned, and quantified from the metagenomic assemblies. These vMAGs were mostly phage, and represented 1,547 unique species-level vOTUs, 247 of which appear to be novel. The metagenomes were also queried for all 3,835 unique species-level vOTUs of DNA viruses with a human host on NCBI Virus, however all but Human betaherpesvirus 7 were at very low abundance in the saliva. The oral viromes of the children with caries exhibited significantly different beta diversity compared to the oral virome of the children with healthy dentition; several vOTUs predicted to infect Pauljensenia and Neisseria were strongly correlated with health, and two vOTUs predicted to infect Saccharibacteria and Prevotella histicola, respectively, were correlated with caries. Co-occurrence analysis indicated that phage typically co-occurred with both their predicted hosts and with bacteria that were themselves associated with the same disease status. Overall, this study provided the sequences of 53 complete or nearly complete novel oral phages and illustrated the significance of the oral virome in the context of dental caries, which has been largely overlooked. This work represents an important step towards the identification and study of phage therapy candidates which treat or prevent caries pathogenesis.

Prevotella histicola ameliorates DSS-induced colitis by inhibiting IRE1α-JNK pathway of ER stress and NF-κB signaling

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.

A randomized, double-blinded, phase 2 trial of EDP1815, an oral immunomodulatory preparation of Prevotella histicola, in adults with mild-to-moderate plaque psoriasis.

Psoriasis is a chronic inflammatory skin disease. EDP1815 is an oral, gut-restricted preparation of non-live Prevotella histicola, the first of a new immunomodulatory therapeutic class targeting the small intestine to generate systemic anti-inflammatory responses. To evaluate safety and efficacy of EDP1815 in mild-to-moderate psoriasis in a proof-of-concept study. A phase 2, multicenter, randomized, double-blinded, placebo-controlled, parallel-group study with a 16-week treatment period and up to 24 weeks of follow-up. Participants were randomized to receive 1, 4, or 10 capsules daily. EDP1815 was well tolerated with comparable rates of treatment-emergent adverse events to placebo, and no drug-related serious adverse events. Clinically meaningful responses to EDP1815, defined as at least 50% reduction in Psoriasis Area and Severity Index (PASI-50) at week 16, were observed in all 3 cohorts, statistically significant in the 1-capsule (29.7%; P = 0.048) and 4-capsule (31.9%; P = 0.022) groups, compared with placebo (12.1%). Among EDP1815-treated PASI-50 responders at week 16, 60% (18/30) maintained or improved off-treatment responses at week 40. Continued off-treatment improvement past 16 weeks shows potential for greater therapeutic benefit that was not assessed. EDP1815 was well-tolerated with a placebo-like safety profile, and had meaningful efficacy outcomes in psoriasis, validating this novel immunomodulatory approach. https://www.clinicaltrials.gov/search?term=NCT04603027, identifier NCT04603027.

Immunomodulating effects of the single bacterial strain therapy EDP1815 on innate and adaptive immune challenge responses — a randomized, placebo-controlled clinical trial

The gut microbiome can modulate systemic inflammation and is therefore target for immunomodulation. Immunomodulating effects of EDP1815, a bacterial commensal strain of Prevotella histicola, were studied in healthy participants. Effects on adaptive immunity were evaluated by a neo-antigen challenge with keyhole limpet haemocyanin (KLH), while effects on innate immunity were evaluated by topical toll-like receptor 7 (TLR7) agonist imiquimod. Capsules with two enteric coating levels (EC1, EC2) were compared. Thirty-six healthy participants were included and received a daily dose of 8 × 1010 cells EDP1815-EC1, EDP1815-EC2 or placebo (randomization 1:1:1) for 60 days. They received KLH vaccinations at days 8, 24 and 36, with intradermal skin challenge at day 57. KLH challenge outcomes were antibody levels, and skin blood flow and erythema after skin challenge, measured by imaging techniques. Imiquimod administration started at day 57, for 72 h. Outcomes consisted of imaging measurements similar to the KLH challenge, and the influx of inflammatory cells and cytokines in blister fluid. There was no effect of EDP1815 treatment on the KLH challenge, neither on the imaging outcomes of the imiquimod challenge. There was a consistently lower influx of inflammatory cells in the blister fluid of EDP1815-treated participants (neutrophils, p = 0.016; granulocytes, p = 0.024), more pronounced in EC1. There was a lower influx of interleukin [IL]-1β, IL-6, IL-8, IL-10, interferon [IFN]-γ and tumour necrosis factor in blister fluid of EDP1815-treated participants. EDP1815 had immunomodulatory effects on the innate immune response driven by imiquimod, but no effect on the KLH challenge was observed. Trial registration number: NCT05682222; date: 22 July 2022.

Gut microbiota in autoimmune and non-autoimmune liver diseases in children

Relevance. The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children - Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose of the study. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Scope and methods of research. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3±4.7 years) was carried out with the identification of the V3-V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Research results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ faeces. The analysis of the conducted studies showed that no dominant taxa were found in the faecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Comparative assessment of intestinal microbiota in autoimmune and non-autoimmune liver diseases in children

The influence of the gut microbiota on the development of various diseases is of great interest to researchers. The conducted studies showed that in patients with chronic liver diseases, the dominant taxa of the gut microbiota were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis, and in healthy children — Neisseria flavescens. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in autoimmune and non-autoimmune liver diseases in children. Purpose. To investigate differences in the taxonomic diversity of fecal microbiota in patients with autoimmune and non-autoimmune liver diseases, as well as to evaluate potential biomarkers of 16S rRNA gene amplicons in these diseases by comparing the taxonomic composition. Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the isolation of the 16S rRNA gene region. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. The analysis of the conducted studies showed that no dominant taxa were found in the fecal samples of children with autoimmune liver diseases, while Veillonella dispar, Veillonella parvula, Cloacibacillus porcorum, Prevotella histicola and Bacteroides eggerthii were the dominant taxa in patients with non-autoimmune liver diseases. Conclusion. Studies have shown differences in the composition of the gut microbiota in children with autoimmune and non-autoimmune liver diseases.

Evaluation of single-strain Prevotella histicola on KLH-driven immune responses in healthy volunteers: A randomized controlled trial with EDP1815

IntroductionEDP1815 is a single-strain of Prevotella histicola with preclinical immunomodulatory properties. The aim of this study was to evaluate pharmacodynamic effects of EDP1815 on the immune response following immunization with keyhole limpet hemocyanin (KLH) and dermal rechallenge. MethodsThirty-two healthy subjects (median 30, range 18–59 years) were randomized over two cohorts to EDP1815 or placebo (12:4). Both cohorts received 8.0 × 1011 total cells daily for 28 days, reconstituted in 10 (A formulation) or 5 (B formulation) capsules. KLH-specific antibodies and circulating regulatory T cells were evaluated. Skin response after rechallenge was assessed with imaging. Immune cell subsets from blister exudates were assessed in the B cohort only. Ex vivo phytohemagglutinin and lipopolysaccharide whole blood challenges were performed to evaluate cytokine release. Gastrointestinal tract persistence, prevalence, and colonization of EDP1815 were assessed by fecal qPCR and microbiome assays. Data were analyzed using repeated measures analysis of covariances. ResultsThere was a trend toward a treatment effect on the KLH-induced skin rechallenge response (CIELab a* estimated difference (ED) −1.50 arbitrary unit (AU), 95% CI −3.47–0.47 AU, P = .13, and average redness ED −0.14 AU, 95% CI −0.31–0.03 AU, P = .10 in B cohort) and, to a lesser extent, on the humoral KLH response. No notable EDP1815 effects were observed on gut persistence, microbiome, and other safety parameters. ConclusionBased on our findings and the clinical benefit observed in the phase 2 study in psoriasis, further investigation of the immunomodulatory effects and potential clinical benefit of EDP1815 is warranted.

Features of the gut microbiota in children with chronic liver diseases

The value of the liver–gut axis is increasingly recognized as a major modulator of autoimmunity. There is no comparative analysis of data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children. Purpose. To investigate the taxonomic diversity of the intestinal microbiota in children with chronic liver diseases compared with healthy patients, to identify differences in bacterial diversity in autoimmune and non-autoimmune liver diseases, as well as the impact of immunosuppressive therapy on the intestinal microbiota. Material and methods. A metagenomic analysis of the gut microbiota of 24 children with chronic liver diseases (mean age 10,3 ± 4,7 years) was carried out with the identification of the V3–V4 region of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The control group consisted of fecal samples of 34 apparently healthy children. Results. When comparing fecal samples of children with autoimmune liver diseases with samples of healthy children, the taxa of Bacteroides dorei, Collinsella aerofaciens, Ruminococcus caffidurs prevailed, and for children of the control group — Neisseria flavescens. When comparing samples of patients with non-autoimmune liver diseases and the control group, it was found that the taxa Bacteroides fragilis, Klebsiella pneumoniae, Bifidobacterium longum prevailed in healthy children. When comparing fecal samples from children with autoimmune and non-autoimmune liver diseases, it was found that Veillonella dispar, Cloacibacillus porcorum, Veillonella parvula, Prevotella histicola and Bacteroides eggerthii taxa dominate in patients with non-autoimmune diseases. No dominant taxa of the gut microbiota were found in children with autoimmune liver diseases. It has been established that the taxa Veillonella dispar, Faecalibacterium prausnitzii, Roseburia inulinivorans, Bacteroides xylanisolvens and Alistipes obesi prevail in patients receiving immunosuppressive therapy, and the taxa Phascolarctobacterium succinatutens, Bacteroides ovatus, Solobacterium mooreis and Holdemanella massilien prevail in patients not receiving immunosuppressive therapy. Conclusion. A recent study of the gut microbiota in children with chronic liver disease shows differences in the imbalance of the gut microbiota compared to the results obtained in adults. The gut microbiota model is capable of distinguishing autoimmune liver diseases from non-autoimmune diseases. Immunosuppressive therapy is accompanied by the dominance of taxa that reduce the production of short-chain fatty acids.

Prevotella histicola Transplantation Ameliorates Cognitive Impairment and Decreases Oxidative Stress in Vascular Dementia Rats.

Vascular dementia is a type of dementia from brain damage caused by cerebrovascular lesions and vascular risk factors. Prevotella histicola is a species of Prevotella, belonging to the category of obligate anaerobe. The purpose of our work was to study the protection of Prevotella histicola on cognitive function in rats subjected to vascular dementia (VaD) and investigate underlying molecular mechanisms. The rats were randomly divided into three groups: control group, 2VO group and 2VO + Prevotella histicola group. The VaD rats (the 2VO group and 2VO + Prevotella histicola group) were generated by bilateral common carotid artery occlusion (2VO). Rats in the 2VO+ Prevotella histicola group were administered with Prevotella histicola twice daily. In comparison with the rats in the 2VO group, rats in the 2VO + Prevotella histicola group presented an enhanced cognitive ability, increased synapse-associated protein expression, a downregulation of proinflammatory factors and an upregulation of neurotrophic factors. The relevant mechanism of the protective effect of Prevotella histicola may be associated with the inhibition of glial cell-associated inflammation by regulating phosphorylation of CaMKII. In conclusion, Prevotella histicola attenuates neurological impairments via regulating synapse-associated protein expression and the liberation of inflammatory elements in vascular dementia rats. The findings above might benefit the development of Prevotella histicola transplantation as a promising treatment of VaD.

Clinical translation of anti-inflammatory effects of Prevotella histicola in Th1, Th2, and Th17 inflammation.

EDP1815 is a non-colonizing pharmaceutical preparation of a single stain of Prevotella histicola isolated from the duodenum of a human donor. We report here preclinical and clinical studies showing that the action of EDP1815, an orally delivered and gut restricted single strain of commensal bacteria can regulate inflammatory responses throughout the body. Supported by evidence for anti-inflammatory activity in three preclinical mouse models of Th1-, TH2-, and Th17-mediated inflammation, EDP1815 was tested clinically in three Phase 1b studies in patients with psoriasis, patients with atopic dermatitis, and healthy volunteers in a KLH skin challenge model. Preclinically, EDP1815 was efficacious in all three mouse models of inflammation, showing reduction in skin inflammation as well as related tissue cytokines. In the Phase 1b studies, EDP1815 was found to be well tolerated by participants, with a safety profile comparable to placebo, including no severe or consistent side-effects reported, and no evidence of immunosuppression with no opportunistic infection occurring in these studies. In psoriasis patients, signs of clinical efficacy were seen after 4 weeks of treatment, which continued beyond the treatment period in the higher-dose cohort. In atopic dermatitis patients, improvements were seen throughout the key physician-and patient-reported outcomes. In a healthy-volunteer study of a KLH-induced skin inflammatory response, consistent anti-inflammatory effects were seen in two cohorts through imaging-based measures of skin inflammation. This is the first report demonstrating clinical effects from targeting peripheral inflammation with a non-colonizing gut-restricted single strain of commensal bacteria, providing proof of concept for a new class of medicines. These clinical effects occur without systemic exposure of EDP1815 or modification of the resident gut microbiota, and with placebo-like safety and tolerability. The breadth of these clinical effects of EDP1815, combined with its excellent safety and tolerability profile and oral administration, suggests the potential for a new type of effective, safe, oral, and accessible anti-inflammatory medicine to treat the wide range of diseases driven by inflammation.Clinical Trial Registration: EudraCT # 2018-002807-32; EudraCT # 2018-002807-32; NL8676; https://clinicaltrials.gov/ct2/show/NCT03733353; http://www.trialregister.nl.

Oral Administration of Human-Gut-Derived Prevotella histicola Improves Sleep Architecture in Rats.

(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 P. histicola (P. histicola group), 5 rats receiving P. stercorea (P. stercorea group), 4 rats not receiving bacteria (No administration group), and 8 rats receiving P. histicola extracellular vesicles (EV) (EV group) during the baseline, administration, and withdrawal periods. (3) Results: The P. histicola 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 (p < 0.01), 13 min for REM sleep (p < 0.05), and 39 min for NREM sleep (p < 0.01) over the baseline. EV administration also increased NREM sleep time on Day 3 of administration (p = 0.05). We observed a linear trend in the dose-response relationship for total sleep and NREM sleep in the P. histicola group. However, neither the no-administration group nor the P. stercorea group showed significant findings. (4) Conclusions: Oral administration of probiotic P. histicola may improve sleep and could be a potential sleep aid. Further rigorous evaluations for the safety and efficacy of P. histicola supplementation are warranted.

Prevotella histicola suppresses ferroptosis to mitigate ethanol-induced gastric mucosal lesions in mice

BackgroundEthanol-induced gastric mucosal lesions (EGML) is one of the most common digestive disorders for which current therapies have limited outcomes in clinical practice. Prevotella histicola (P. histicola) has shown probiotic efficacy against arthritis, multiple sclerosis and oestrogen deficiency-induced depression in mice; however, its role in EGML remains unclear in spite of its extensive colonisation of the stomach. Ferroptosis, which is characterised by lipid peroxidation, may be involved in EGML. Herein, we aimed to investigate the effects and underlying mechanism of action of P. histicola on EGML in the ferroptosis-dependent pathway.MethodsP. histicola was intragastrically administered for a week, and deferoxamine (DFO), a ferroptosis inhibitor, was intraperitoneally injected prior to oral ethanol administration. The gastric mucosal lesions and ferroptosis were assessed via histopathological examinations, quantitative real-time PCR, Western blot, immunohistochemistry and immunofluorescence.ResultsP. histicola was originally found to attenuate EGML by reducing histopathological changes and lipid reactive oxygen species (ROS) accumulation. The pro-ferroptotic genes of Transferrin Receptor (TFR1), Solute Carrier Family 39 Member 14 (SLC39A14), Haem Oxygenase-1 (HMOX-1), Acyl-CoA Synthetase Long-chain Family Member 4 (ACSL4), Cyclooxygenase 2 (COX-2) and mitochondrial Voltage-dependent Anion Channels (VDACs) were up-regulated; the anti-ferroptotic System Xc-/Glutathione Peroxidase 4 (GPX4) axis was inhibited after ethanol administration. However, the changes of histopathology and ferroptosis-related parameters induced by ethanol were reversed by DFO. Furthermore, P. histicola treatment significantly downregulated the expression of ACSL4, HMOX-1 and COX-2, as well as TFR1 and SLC39A14, on mRNA or the protein level, while activating the System Xc-/GPX4 axis.ConclusionsWe found that P. histicola reduces ferroptosis to attenuate EGML by inhibiting the ACSL4- and VDAC-dependent pro-ferroptotic pathways and activating the anti-ferroptotic System Xc-/GPX4 axis.

The Preventive Effects of Probiotic Prevotella histicola on the Bone Loss of Mice with Ovariectomy-Mediated Osteoporosis.

It has been demonstrated that the disturbance of gut microbiota (GM) is closely related to the reduction of bone mass and incidence of osteoporosis (OP). The aim of this study is to investigate whether the supplementation of Prevotella histicola (Ph) can prevent the bone loss in mice with ovariectomy (OVX)-mediated OP, and further explore relevant mechanisms. Regular (once a day for 8 consecutive weeks) and quantitative (200 µL/d) perfusion of Ph (the bacteria that orally gavaged) was conducted starting from 1 week after the construction of mice models. Bone mass and bone microstructure were detected by Micro-computed tomography (Micro-CT). Expressions of intestinal permeability, pro-inflammatory cytokines, and osteogenic and osteoclastic activities of mice were analyzed by histological staining and immunohistochemistry (IHC). 16S rRNA high throughput sequencing technique was applied to analyze the alterations of composition, abundance, and diversity of collected feces. Regular and quantitative perfusion of Ph mitigated the bone loss in mice with OVX-mediated OP. Compared with OVX + PBS group, perfusion of Ph repressed osteoclastogenesis and promoted osteogenesis, reduced release of pro-inflammatory cytokine cytokines (interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α)), and reversed expressions of tight junction proteins (zonula occludens protein 1 (ZO-1) and Occludin). Besides, the perfusion of Ph improved the composition, abundance, and diversity of GM. Collectively, this study revealed that regular and quantitative perfusion of Ph can improve the bone loss in mice with OVX-mediated OP by repairing intestinal mucosal barrier damage, optimizing intestinal permeability, inhibiting release of pro-osteoclastogenic cytokines, and improving disturbance of GM.

Prevotella histicola Prevented Particle-Induced Osteolysis via Gut Microbiota-Dependent Modulation of Inflammation in Ti-Treated Mice.

Wear particles generated from total joint replacements induce chronic osteolysis mediated by inflammatory upregulation, which leads to implant failure. Recent studies have suggested an important role of the gut microbiota in modulating the host's metabolism and immune system, leading to alterations in bone mass. Following gavage with P. histicola, micro-CT and HE staining revealed that osteolysis was significantly reduced in titanium (Ti)-treated mice. Immunofluorescence analysis revealed an increased macrophage (M)1/M2 ratio in the guts of Ti-treated mice, which decreased when P. histicola was added. P. histicola was also found to upregulate the tight junction proteins ZO-1, occludin, claudin-1, and MUC2 in the gut, reduce the levels of inflammatory factors IL-1β, IL-6, IL-8, and TNF-α, primarily in the ileum and colon, and decrease the expression of IL-1β and TNF-α and increase the level of IL-10 in the serum and cranium. Furthermore, P. histicola treatment resulted in a significant downregulation of CTX-1, RANKL, and RANKL/OPG. These findings demonstrate that P. histicola significantly mitigates osteolysis in Ti-treated mice by improving intestinal microbiota that repairs intestinal leakage and reduces systemic and local inflammation which in turn inhibits RANKL expression for bone resorption. P. histicola treatment may thus be therapeutically beneficial for particle-induced osteolysis.

On the Oral Microbiome of Oral Potentially Malignant and Malignant Disorders: Dysbiosis, Loss of Diversity, and Pathogens Enrichment.

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 (n = 9), PVL (n = 12), OSCC (n = 10), PVL-OSCC (n = 8), and healthy (n = 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 Fusobacteriota constituted more than 30% of the microbiome. PVL and PVL-OSCC patients had a higher abundance of Campilobacterota and lower Proteobacteria than any other group analyzed. A penalized regression was performed to determine which species were able to distinguish groups. HL is enriched in Streptococcus parasanguinis, Streptococcus salivarius, Fusobacterium periodonticum, Prevotella histicola, Porphyromonas pasteri, and Megasphaera micronuciformis; PVL is enriched in Prevotella salivae, Campylobacter concisus, Dialister pneumosintes, and Schaalia odontolytica; OSCC is enriched in Capnocytophaga leadbetteri, Capnocytophaga sputigena, Capnocytophaga gingivalis, Campylobacter showae, Metamycoplasma salivarium, and Prevotella nanceiensis; and PVL-OSCC is enriched in Lachnospiraceae bacterium, Selenomonas sputigena, and Prevotella shahii. 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.

Study of oral microbiota diversity among groups of families originally from different countries

The diversity of oral microbiota is affected by diets habits, gender, age, ethnic group, and environment. The acquisition of oral microbiota and the role of family on oral microbiota development is poorly understood. This study aims to characterize and compare the oral bacterial microbiota among families using 16S rRNA gene sequencing. This work was conducted in Jeddah city from 2020 to 2021, in which four families composed of 20 members of different ethnicity and lifestyle were recruited. After the collection of saliva samples, the DNA was extracted and processed for 16S rRNA gene metagenomics sequencing. Among 378 OUTs generated, 39 (10.3%) were unique in group A, 13 (3.4%) unique in group B, and 11 (2.9%) were unique in groups C and D. We observed a significant variation at the level of top abundance phylum (14), families (23), genera (24), and species (22) of bacteria among family members. Within family groups, different bacterial species were reported to be more dominant among certain family members than the other; Prevotella melaninogenica, Prevotella histicola and Haemophilus parainfluenzae, Veillonella atypica, Porphyromonas pasteri and Haemophilus pittmaniae were more dominant in parents of some families than the other family member. In summary, this study highlights the precise and perceptible association of oral microbial between family members. Our findings documented the clustering of certain bacterial species in family groups, supporting the role of community in the development of oral microbiota.

Multimodal Data Integration Reveals Mode of Delivery and Snack Consumption Outrank Salivary Microbiome in Association With Caries Outcome in Thai Children.

Early childhood caries (ECC) is not only the most common chronic childhood disease but also disproportionately affects underserved populations. Of those, children living in Thailand have been found to have high rates of ECC and severe ECC. Frequently, the cause of ECC is blamed on a handful of cariogenic organisms, such as Streptococcus mutans and Streptococcus sobrinus. However, ECC is a multifactorial disease that results from an ecological shift in the oral cavity from a neutral pH (~7.5) to an acidic pH (<5.5) environment influenced by the host individual’s biological, socio-behavioral, and lifestyle factors. Currently, there is a lack of understanding of how risk factors at various levels influence the oral health of children at risk. We applied a statistical machine learning approach for multimodal data integration (parallel and hierarchical) to identify caries-related multiplatform factors in a large cohort of mother-child dyads living in Chiang Mai, Thailand (N=177). Whole saliva (1 mL) was collected from each individual for DNA extraction and 16S rRNA sequencing. A set of maternal and early childhood factors were included in the data analysis. Significantly, vaginal delivery, preterm birth, and frequent sugary snacking were found to increase the risk for ECC. The salivary microbial diversity was significantly different in children with ECC or without ECC. Results of linear discriminant analysis effect size (LEfSe) analysis of the microbial community demonstrated that S. mutans, Prevotella histicola, and Leptotrichia hongkongensis were significantly enriched in ECC children. Whereas Fusobacterium periodonticum was less abundant among caries-free children, suggesting its potential to be a candidate biomarker for good oral health. Based on the multimodal data integration and statistical machine learning models, the study revealed that the mode of delivery and snack consumption outrank salivary microbiome in predicting ECC in Thai children. The biological and behavioral factors may play significant roles in the microbial pathobiology of ECC and warrant further investigation.

Persistent Pulmonary Interstitial Emphysema With Respiratory Infection: A Clinicopathological Analysis of Six Cases and Detection of Infectious Pathogens by Metagenomic Next-Generation Sequencing (mNGS).

BackgroundPersistent pulmonary interstitial emphysema (PPIE) is known to be related to mechanical ventilation and preterm. However, PPIE is also reported rarely in non-ventilated and full-term infants. Its relationship with respiratory infection is rarely reported in the literature. PPIE is difficult to diagnose and always mimics other congenital thoracic malformations (CTMs), such as congenital cystic adenomatoid malformation (CCAM).ObjectiveThe objective of this study was to evaluate clinicopathological and radiographic features of PPIE with respiratory infection and to detect the possible infectious pathogens.MethodsFrom January 2011 to December 2019, six cases were confirmed pathologically with PPIE from a large cohort of 477 resected CTMs in West China Hospital of Sichuan University. Clinical and radiographic features were obtained from patients' medical records and follow-up. The present study aimed to analyze clinicopathological and radiographic features and to detect the infectious pathogens by metagenomic next-generation sequencing (mNGS).ResultsThe six PPIE cases included four girls and two boys, ranging from 2 months to 5 years; 100% (5/5) of the available cases were full-term and without mechanical ventilation. CCAM were suspected in 66.7% (4/6) patients; 66.7% (4/6) cases affected a single lobe, and 33.3% (2/6) cases affected both lung lobes. Clinically, all six PPIEs were presented with symptoms of respiratory infection and diagnosed with pneumonia. All six patients were treated by surgery after anti-infective treatment. The pathologic characteristics showed lung cysts with variable size along the bronchovascular bundles, the cysts had a discontinuous fibrotic wall with a smooth inner surface lined with uninucleated and/or multinucleated macrophages. Streptococcus pneumoniae was detected in patient No. 1. Human beta-herpesvirus 5 was detected in patient No. 2. Neisseria mucosa, Neisseria sicca, Prevotella melaninogenica, Prevotella histicola, and Fusobacterium nucleatum were detected in patient No. 5, and no infectious pathogen was detected in 50% (3/6, No. 3, No. 4, and No. 6) of cases.ConclusionSix rare cases of PPIE with respiratory infection were treated by surgery after anti-infective treatment. All five available cases were full-term infants without mechanical ventilation. The histological characteristics of PPIE were the wall of cysts composed of a thin layer of discontinuous fibrous tissue and lined with uninucleated or/and multinucleated macrophages.