Unraveling brain aging through the lens of oral microbiota

The oral cavity is a complex physiological community encompassing a wide range of microorganisms.Dysbiosis of oral microbiota can lead to various oral infectious diseases,such as periodontitis and tooth decay,and even affect systemic health,including brain aging and neurodegenerative diseases.Recent studies have highlighted how oral microbes might be involved in brain aging and neurodegeneration,indicating potential avenues for intervention strategies.In this review,we summarize clinical evidence demonstrating a link between oral microbes/oral infectious diseases and brain aging/neurodegenerative diseases,and dissect potential mechanisms by which oral microbes contribute to brain aging and neurodegeneration.We also highlight advances in therapeutic development grounded in the realm of oral microbes,with the goal of advancing brain health and promoting healthy aging.

Adjuvant postbiotic administration improves dental caries prognosis by restoring the oral microbiota

Conventional filling therapy fails to fundamentally reduce oral cariogenic bacteria.Thus,oral microbiota follow-up intervention after filling would be necessary for improving dental caries prognosis.We recruited 9 caries-free individuals,and 89 dental caries subjects(5 dropouts).Eighty-nine patients were randomized into three groups:caries(n=8;no treatment),control(n=40;filling),and postbiotics(n=41;filling and 14-day Probio-Eco®intervention).Salivary samples were collected at 0 day(after filling)and 14 days.Our results showed that the diversity of dental caries oral microbiota was significantly increased compared with healthy subjects,and filling could restore a healthier oral microbiota partially and temporarily.Thepostbiotics intervention keeps a low alpha-diversity.Co-occurrence network analysis showed that a more stable oral microbiota structure after postbiotics intervention.Taxonomic and functional annotation of the microbiota revealed that postbiotics co-treatment significantly:increased the relative abundance of Pseudomonas and P.reactans,decreased the relative abundance of Prevotella shahii,and enriched the energy metabolism-related pathways.BugBase-predicted phenotypes inferred to an oral microbiota with decreased potential pathogenic bacteria and increased oxidative stress-tolerant bacteria after postbiotics intervention.Collectively,it suggested that postbiotics co-treatment could be a promising strategy that restores the oral microecological balance for dental caries.

The bacterial small RNAs: The new biomarkers of oral microbiotaassociated cancers and diseases

The oral microbiota is a vital part of the human microbiota that functions in various physiological processes and ishighly relevant to cancers and other diseases. With the alterations of host immune competence, the homeostatic balanceexisting between the oral microbiota and host may be disturbed and result in the development of diseases. Numerousobservations have suggested that small RNAs are key regulators of bacterial pathogenesis and bacteria-host interactions.Further, bacterial small RNAs are considered to be promising biomarkers for the development of novel, and efficacioustherapies for oral dysbiosis. Mechanistic insights into how oral pathogens communicate with other bacteria or host cellsin oral cancers via small RNAs are hot topics of research. Current studies also have begun to elucidate the key role oforal microbiota in the development of systemic diseases. This article discusses existing findings and nascent mechanismsgoverning the small RNA-based interactions between oral microbiota and associated diseases. The knowledge of suchinteractions is key in planning approaches to reverse dysbiosis to achieve health.

Oral microbiota:A new view of body health

Oral microbiota is an important part of the human microbiota.Oral microbes can be colonized into the intestine in various ways.Oral microbiota is associated with a variety of oral diseases.Recently,increasing evidence has shown that the oral microbiota is closely related to the physical state of humans,such as diabetes,obesity,and cancer.In the future,oral microbiota will become a new target for improving the physical state of humans.

Oral microbiota in the oral-genitourinary axis:identifying periodontitis as a potential risk of genitourinary cancers

Periodontitis has been proposed as a novel risk factor of genitourinary cancers:although periodontitis and genitourinary cancers are two totally distinct types of disorders,epidemiological and clinical studies,have established associations between them.Dysbiosis of oral microbiota has already been established as a major factor contributing to periodontitis.Recent emerging epidemiological evidence and the detection of oral microbiota in genitourinary organs indicate the presence of an oral-genitourinary axis and oral microbiota may be involved in the pathogenesis of genitourinary cancers.Therefore,oral microbiota provides the bridge between periodontitis and genitourinary cancers.We have carried out this narrative review which summarizes epidemiological studies exploring the association between periodontitis and genitourinary cancers.We have also highlighted the current evidence demonstrating the capacity of oral microbiota to regulate almost all hallmarks of cancer,and proposed the potential mechanisms of oral microbiota in the development of genitourinary cancers.

Oral microbiota and host innate immune response in bisphosphonate-related osteonecrosis of the jaw

Bacterial biofilms have emerged as potential critical triggers in the pathogenesis of bisphosphonate（BP）-related osteonecrosis of the jaw（ONJ） or BRONJ. BRONJ lesions have shown to be heavily colonized by oral bacteria, most of these difficult to cultivate and presents many clinical challenges. The purpose of this study was to characterize the bacterial diversity in BRONJ lesions and to determine host immune response. We examined tissue specimens from three cohorts（n530）; patients with periodontal disease without a history of BP therapy（Control, n510）, patients with periodontal disease having history of BP therapy but without ONJ（BP, n55） and patients with BRONJ（BRONJ, n515）. Denaturing gradient gel electrophoresis of polymerase chain reaction（PCR）-amplified 16 S r RNA gene fragments revealed less bacterial diversity in BRONJ than BP and Control cohorts. Sequence analysis detected six phyla with predominant affiliation to Firmicutes in BRONJ（71.6%）, BP（70.3%） and Control（59.1%）. Significant differences（P,0.05） in genera were observed, between Control/BP, Control/BRONJ and BP/BRONJ cohorts. Enzyme-linked immunosorbent assay（ELISA）results indicated that the levels of myeloperoxidase were significantly lower, whereas interleukin-6 and tumor necrosis factor-alpha levels were moderately elevated in BRONJ patients as compared to Controls. PCR array showed significant changes in BRONJ patients with downregulation of host genes, such as nucleotide-binding oligomerization domain containing protein 2, and cathepsin G, the key modulators for antibacterial response and upregulation of secretory leukocyte protease inhibitor, proteinase 3 and conserved helix–loop–helix ubiquitous kinase. The results suggest that colonization of unique bacterial communities coupled with deficient innate immune response is likely to impact the pathogenesis of ONJ.

Effects of <i>Streptococcus salivarius</i>K12 on Experimental Periodontitis and Oral Microbiota in Mice

Background: Periodontal diseases comprise a wide range of inflammatory conditions that affect the supporting structures of the teeth, and may lead to severe periodontal destruction and even tooth loss.?Streptococcus salivarius K12 (S. salivarius K12), one of oral probiotics, has been reported to be able to inhibit various potentially deleterious bacteria. This study was the first time to investigate the effects of S. salivarius K12 on ligature-induced periodontitis in mice. Methods: A silk ligature was tied around the second left maxillary molar to establish the model of periodontitis, and then, mice in group S. salivarius K12 were administered with S. salivarius K12 (2 x 109 CFU) twice daily for 30 d, the others were treated with isopyknic water. Results: Administration with S. salivarius K12 markedly decreased the anaerobic bacteria accumulation on the teeth, and it also considerably alleviated periodontitis-induced alveolar bone resorption and attachment loss. Moreover, S. salivarius K12 administration increased the relative species abundance of Gram-positive bacterium in oral cavity while decreased Gram-negative bacterium, as well as the diversity of the bacterial community. Conclusion: Oral administration of the probiotic S. salivarius K12 may mitigate the alveolar bone resorption and attachment loss of periodontitis by modulating the oral microbiota.

Oral Microbiota:A New Insight into Cancer Progression,Diagnosis and Treatment

The polymorphic microbiome has been defined as one of the“Hallmarks of Cancer”.Extensive studies have now uncovered the role of oral microbiota in cancer development and progression.Bacteria,fungi,archaea,and viruses in the oral cavity interact dynamically with the oral microenvironment to maintain the oral micro-ecological homeostasis.This complex interaction is influenced by many factors,such as maternal transmission,personal factors and environmental factors.Dysbiosis of oral microbiota can disturbed this host-microbiota interaction,leading to systemic diseases.Numerous studies have shown the potential associations between oral microbiota and a variety of cancers.However,the underlying mechanisms and therapeutic insights are still poorly understood.In this review,we mainly focus on the following aspects:(1)the factors affect oral microbiota composition and function;(2)the interaction between microenvironment and oral microbiota;(3)the role of multi-kingdom oral microbiota in human health;(4)the potential underlying mechanisms and therapeutic benefits of oral microbiota against cancer.Finally,we aim to describe the impact of oral microbiota on cancer progression and provide novel therapeutic insights into cancer prevention and treatment by targeting oral microbiota.

Oral microbiota accelerates corrosion of 316L stainless steel for orthodontic applications

In this work,microbiologically influenced corrosion(MIC)of 316 L stainless steel(SS)caused by oral microbiota was investigated with HOMINGS 16 S rRNA gene sequencing technology,and electrochemical and surface analysis techniques.The results showed that oral microbiota from different subjects developed multi-species biofilms with significant differences in structure and composition of bacteria strains on the316 L SS coupons.In the presence of oral microbiota,more severe pitting corrosion and faster dissolution of metallic ions including Ni and Cr were observed.The biofilm considerably decreased the pitting potential of 316 L SS from 1268.0±29.1 mV vs.SCE(abiotic control)to less than 500 mV vs.SCE.The corrosion current density in the presence of oral microbiota from subject 1(115.3±83.3 nA cm^(-2))and subject 2(184.4±162.0 nA cm^(-2))was at least 4 times more than that in the abiotic medium(28.0±2.3 nA cm^(-2)).The electroactive microorganisms with the potential to facilitate corrosion via extracellular electron transfer found in oral microbiota may be mainly responsible for the accelerated corrosion.

急性胰腺炎的营养支持治疗研究进展

急性胰腺炎是常见的消化系统疾病,营养支持治疗是急性胰腺炎患者治疗过程的基础。在轻度急性胰腺炎患者中,早期经口喂养可以缩短住院时间,降低住院费用并减少并发症。如果对经口喂养无法耐受,应在24~72 h内提供营养治疗,肠内营养是首选方式。肠内营养可通过胃或空肠喂养给药,具体给药途径取决于消化耐受性和是否存在肠梗阻。肠道益生菌可预防细菌移位和胰腺坏死感染,肠道菌群移植为急性胰腺炎的治疗提供了新的方案。

低温杀菌乳对人体口腔菌群的影响

为了研究低温奶对口腔菌群的影响,本试验采用随机对照研究,招募27名志愿者,随机分到低温杀菌乳组(FP)和高温杀菌乳(UHT)组,每日统一膳食,第4~10天增加不同乳品干预,第1、4、7、10天采集唾液后进行16S rRNA测序。结果显示,统一膳食3天后,两组口腔菌差异缩小;乳品干预后,两组之间α多样性无显著差异,β多样性指数差异显著;统一饮食并干预7 d后,FP组和UHT组间差异菌数量增加,FP组梭杆菌门(Fusobacteriota)、普氏菌属(Prevotella)、糖杆菌TM7x、口腔杆菌属(Stomatobaculum)、贫养菌属(Abiotrophia)、Clostridia-UCG-014、链杆菌属(Streptobacillus)等丰度显著高于UHT组,UHT组乳杆菌属(Lactobacillus)高于FP组。肠道菌功能预测表明,UHT组第10天的氨基酸代谢和信号转导功能丰度高于FP组。乳品干预显著改善了口腔菌,低温杀菌乳有助于提高具有潜在益生功能的Clostridia-UCG-014的丰度,高温杀菌乳有助于益生菌乳杆菌属(Lactobacillus)的丰度。

口腔疾病与抑郁症的关系

口腔健康是身心健康的重要组成部分。口腔是与外界交流的渠道,具有表达紧张、悲观等情绪的功能。口腔疾病可引发抑郁情绪,抑郁症也可导致口腔疾病的恶化。作为人体微生物群落的重要组成部分,口腔微生态失衡可释放口腔病原微生物,通过循环、神经、免疫系统等途径,传递到大脑,对中枢神经系统的功能产生重大影响,导致下丘脑⁃垂体⁃肾上腺(hypothalamic⁃pituitary⁃adrenal axis,HPA)轴失调,加重抑郁发展。同样,抑郁症患者口腔微生态的失衡,会加剧口腔疾病的发生。抑郁症与口腔疾病之间的关系并非孤立存在,而是相互影响、互为因果的复杂过程。为揭示两者之间的因果关系,并制定预防、治疗这两种疾病的共同策略,本文从口腔微生物角度探讨口腔疾病与抑郁症之间的互作机制:龋病、牙髓根尖周病和牙周病的发生与口腔内特定细菌的过度增殖密切相关,如变异链球菌、牙龈卟啉单胞菌、罗氏菌等,可通过不完整或受损的血脑屏障直接侵入大脑,激活促炎细胞因子,导致神经炎症,从而加重抑郁症状;口腔黏膜的炎症和溃疡由多种因素引起,包括感染、免疫异常等;由于抑郁症患者的免疫系统功能受损,这些炎症反应往往更为剧烈且难以控制;错畸形、三叉神经痛和颞下颌关节病等患者心理压力和免疫系统的变化,也会增加抑郁症的发生风险。未来需要探索抑郁症患者口腔微生态的治疗潜力,通过调整口腔微生态来改善抑郁症的症状和治疗效果,为抑郁症的预防和治疗提供新途径。

小檗碱、口腔菌群、系统性疾病三者相关性的研究进展

小檗碱具有抗菌、抗炎作用,是常用的传统中药之一。近年来多项研究证实小檗碱对心血管疾病、糖尿病、神经系统疾病等系统性疾病有较好的治疗效果,口腔菌群也与这些系统性疾病的发生发展存在密切联系。本文就小檗碱、口腔菌群、系统性疾病之间的相关性进行综述,为治疗系统性疾病提供新思路。

口腔微生物与食管疾病关系的研究进展

口腔微生物与人类疾病的相关性是近年来的研究热点。口腔微生物除了与口腔疾病具有密切关系外,还与消化道其他器官疾病密切相关,其中食管疾病很少受到关注。本文旨在总结当前口腔微生物组与食管疾病之间关联的证据,这些证据表明与胃食管反流病、巴雷特食管、食管鳞状细胞癌和食管腺癌相关的口腔微生物组具有独有的特征,这种从较高革兰阳性菌比例到革兰阴性菌更占优势的转变被认为与食管疾病的发生发展有关。口腔微生物组改变与食管疾病的关联机制可能是由于革兰阴性菌脂多糖的表达,特别是福赛斯坦纳菌和牙龈卟啉单胞菌参与食管癌发展的信号通路。识别口腔微生物组的改变将会促进临床对食管疾病病因、发病机制和进展的理解,促进新诊断方法出现,并为制订个性化治疗方案奠定基础。

Oral frailty and neurodegeneration in Alzheimer’s disease

Frailty is a critical intermediate status of the aging process with a multidimensional and multisystem nature and at higher risk for adverse health-related outcomes,including falls,disability,hospitalizations,institutionalization,mortality,dementia,and Alzheimer’s disease.Among different frailty phenotypes,oral frailty has been recently suggested as a novel construct defined as a decrease in oral function with a coexisting decline in cognitive and physical functions.We briefly reviewed existing evidence on operational definitions of oral frailty,assessment and screening tools,and possible relationships among oral frailty,oral microbiota,and Alzheimer’s disease neurodegeneration.Several underlying mechanism may explain the oral health-frailty links including undernutrition,sarcopenia linked to both poor nutrition and frailty,psychosocial factors,and the chronic inflammation typical of oral disease.Oral microbiota may influence Alzheimer’s disease risk through circulatory or neural access to the brain and the interplay with periodontal disease,often causing tooth loss also linked to an increased Alzheimer’s disease risk.On this bases,COR388,a bacterial protease inhibitor targeting Porphyromonas gingivalis implicated in periodontal disease,is now being tested in a double-blind,placebocontrolled Phase II/III study in mild-to-moderate Alzheimer’s disease.Therefore,oral status may be an important contributor to general health,including Alzheimer’s disease and latelife cognitive disorders,suggesting the central role of preventive strategies targeting the novel oral frailty phenotype and including maintenance and improvement of oral function and nutritional status to reduce the burden of both oral dysfunction and frailty.

胰腺癌患者口腔菌群多样性组成谱的系统评价

目的系统评价胰腺癌患者口腔菌群多样性组成谱。方法通过PubMed、Web of science、EMbase、The Cochrane Library、CBM、中国知网、万方和维普数据库检索胰腺癌患者口腔菌群多样性组成谱的横断面研究,检索时限从建库至2023年7月15日。根据纳入排除标准筛选评价文献、提取数据和信息,采用定性系统评价和Review Manager 5.4进行Meta分析。结果最终纳入7个横断面研究,包括187例胰腺癌患者,440例健康对照者。Meta分析结果显示,与健康对照者相比,胰腺癌患者口腔菌群ɑ多样性Simpson指数降低。定性分析显示胰腺癌患者的厚壁菌门、普氏菌属、罗斯氏菌属、链球菌属的相对丰度高于健康者;胰腺癌患者的变形菌门、奈瑟菌属、嗜血杆菌属、卟啉单胞菌属、副流感嗜血杆菌的相对丰度低于健康者。结论胰腺癌患者口腔菌群具有一定的特异性,其中厚壁菌门、普氏菌属等在胰腺癌患者中相对丰度较高;而变形菌门、奈瑟菌属等在胰腺癌患者中的相对丰度较低。

拉曼光谱在口腔细菌鉴定中的应用

口腔细菌与龋病、牙周病、口腔癌等多种口腔疾病相关,部分致病菌还在系统性疾病的发生发展中起重要作用,细菌病原体的快速鉴定有助于口腔疾病的诊断和精准治疗。拉曼光谱是一种简单、快速、无创的新型检测技术,可以提供大量详细的细菌信息,能快速鉴定细菌,但该技术在口腔临床中的应用目前较少,仍需进一步的探索。本文总结了拉曼光谱在鉴定口腔细菌中的研究进展,探讨了其临床应用的前景和挑战。

Characterization of oral bacterial diversity of irradiated patients by high-throughput sequencing

The objective of this study was to investigate the compositional profiles and microbial shifts of oral microbiota during head-and-neck radiotherapy.Bioinformatic analysis based on 16S rRNA gene pyrosequencing was performed to assess the diversity and variation of oral microbiota of irradiated patients.Eight patients with head and neck cancers were involved in this study.For each patient, supragingival plaque samples were collected at seven time points before and during radiotherapy.A total of 147 232 qualified sequences were obtained through pyrosequencing and bioinformatic analysis,representing 3 460 species level operational taxonomic units(OTUs) and 140 genus level taxa.Temporal variations were observed across different time points and supported by cluster analysis based on weighted UniFrac metrics.Moreover,the low evenness of oral microbial communities in relative abundance was revealed by Lorenz curves.This study contributed to a better understanding of the detailed characterization of oral bacterial diversity of irradiated patients.

Oral microbiome and pancreatic cancer

BACKGROUND Microbiota profiles differ between patients with pancreatic cancer and healthy people,and understanding these differences may help in early detection of pancreatic cancer.Saliva sampling is an easy and cost-effective way to determine microbiota profiles compared to fecal and tissue sample collection.AIM To investigate the saliva microbiome distribution in patients with pancreatic adenocarcinoma(PDAC)and the role of oral microbiota profiles in detection and risk prediction of pancreatic cancer.METHODS We conducted a prospective study of patients with pancreatic cancer(n=41)and healthy individuals(n=69).Bacterial taxa were identified by 16S ribosomal ribonucleic acid gene sequencing,and a linear discriminant analysis effect size algorithm was used to identify differences in taxa.Operational taxonomic unit values of all selected taxa were converted into a normalized Z-score,and logistic regressions were used to calculate risk prediction of pancreatic cancer.RESULTS Compared with the healthy control group,carriage of Streptococcus and Leptotrichina(z-score)was associated with a higher risk of PDAC[odds ratio(OR)=5.344,95%confidence interval(CI):1.282-22.282,P=0.021 and OR=6.886,95%CI:1.423-33.337,P=0.016,respectively].Veillonella and Neisseria(z-score)were considered a protective microbe that decreased the risk of PDAC(OR=0.187,95%CI:0.055-0.631,P=0.007 and OR=0.309,95%CI:0.100-0.952,P=0.041,respectively).Among the patients with PDAC,patients reporting bloating have a higher abundance of Porphyromonas(P=0.039),Fusobacterium(P=0.024),and Alloprevotella(P=0.041);while patients reporting jaundice had a higher amount of Prevotella(P=0.008);patients reporting dark brown urine had a higher amount of Veillonella(P=0.035).Patients reporting diarrhea had a lower amount of Neisseria and Campylobacter(P=0.024 and P=0.034),and patients reporting vomiting had decreased Alloprevotella(P=0.036).CONCLUSION Saliva microbiome was able to distinguish patients with pancreatic cancer and healthy individuals.Leptotrichia may be specific for patients living in Sichuan Province,southwest China.Symptomatic patients had different bacteria profiles than asymptomatic patients.Combined symptom and microbiome evaluation may help in the early detection of pancreatic cancer.

复方苦参注射液对重度放射性口腔黏膜炎患者的临床疗效观察

目的探讨复方苦参注射液(compound Kushen injection,CKI)对重度放射性口腔黏膜炎(radiation-induced oral mucositis,RIOM)患者治疗效果和对口腔菌群的影响。方法选取2022年3月至2023年3月黄石市中心医院行调强放疗且发生重度RIOM的鼻咽癌患者96例,采用随机数字表法分为对照组和观察组,每组48例。对照组采用常规治疗,观察组在对照组基础上联合应用CKI。比较两组患者临床疗效、口腔溃疡持续时间、中医症状积分,口腔韦永氏球菌、链球菌和奈瑟氏菌菌群数量及唾液TNF-α、IL-1β和IL-6水平。结果96例患者中,男57例,女39例,年龄18~72岁,平均(59.2±11.9)岁。观察组总有效率高于对照组(89.58%比62.50%);口腔溃疡持续时间低于对照组[(6.48±1.37)d比(10.74±2.86)d];治疗后两组中医症状积分、唾液TNF-α、IL-1β和IL-6水平均低于治疗前,且观察组低于对照组;口腔韦永氏球菌、链球菌和奈瑟氏菌菌群数量均高于治疗前,且观察组高于对照组,差异均有统计学意义(P<0.05)。结论CKI对重度RIOM患者有较好的治疗效果,能促进口腔黏膜愈合,改善中医症状,恢复口腔菌群平衡,缓解口腔黏膜炎症。